Molecular And Cellular Biochemistry[JOURNAL]
Sun
200 papers
Ubiquitin's code: UPS orchestrating DNA repair and genomic stability under genotoxic stress.
Roy S, Saha G, Basu M … +1 more , Ghosh MK
Mol Cell Biochem · 2026 Jun · PMID 42118426 · Publisher ↗
The genetic blueprint of life faces ongoing threats from physical and chemical agents that can disrupt DNA and lead to genomic instability, which is one of the hallmarks of cancer. These agents include external factors l...
The genetic blueprint of life faces ongoing threats from physical and chemical agents that can disrupt DNA and lead to genomic instability, which is one of the hallmarks of cancer. These agents include external factors like ionizing radiation, UV radiation, radiotherapy, and chemotherapeutic drugs or internal factors like redox imbalance arising from deregulated cellular metabolism. These agents damage DNA by generating inter-strand crosslinks, DNA-protein crosslinks, bulky adducts or double-strand breaks that ultimately decreases genomic integrity and leads to tumorigenesis. The coordinated actions of E3 ubiquitin ligases and deubiquitinases (DUBs) are essential in the precise control of these DNA damage tolerance and repair pathways. This has unravelled vulnerable points for intervention in cancer chemoresistance, since it has been observed that these ubiquitinases and deubiquitinases may upregulate repair proteins that reverses DNA damage conferred by conventional chemotherapeutics. This review focusses on the intricate dynamics of ubiquitination and deubiquitination in controlling DNA damage repair pathways and safeguarding genomic integrity.
Puerarin alleviates myocardial ischemia-reperfusion injury by enhancing FUNDC1-mediated mitophagy.
Feng N, Zhang A, Yao L … +11 more , Tang J, Lu M, Shi D, Zhu Z, Liu R, Chen J, Min X, Yang H, Xu H, Zhang W, He X
Mol Cell Biochem · 2026 May · PMID 42118425 · Publisher ↗
Myocardial ischemia‑reperfusion injury (I/R) is a major contributor to adverse outcomes in ischemic heart disease. Mitochondrial dysfunction plays a central role in I/R, and modulating mitophagy has shown potential in at...
Myocardial ischemia‑reperfusion injury (I/R) is a major contributor to adverse outcomes in ischemic heart disease. Mitochondrial dysfunction plays a central role in I/R, and modulating mitophagy has shown potential in attenuating such injury. Nevertheless, whether puerarin influences mitophagy during I/R remains poorly understood. An in vivo I/R (30 min/24 h) model was established in C57BL/6 mice after 7 day puerarin pretreatment. In vitro, a hypoxia‑reoxygenation H/R (8 h/4 h) model was constructed using H9c2 cardiomyocytes. Cardiac function was assessed by echocardiography, infarct size was determined via Evans Blue‑TTC staining, mitophagy was visualized by transmission electron microscopy, and expression of mitophagy‑related proteins was evaluated by western blot. Puerarin significantly reduced I/R‑induced damage in both models. It attenuated mitochondrial depolarization and reactive oxygen species generation, increased mitophagic activity, and upregulated the mitophagy receptor FUNDC1. Puerarin alleviates myocardial ischemia‑reperfusion injury by enhancing FUNDC1‑mediated mitophagy, particularly during early reperfusion. These results reveal a key mechanism underlying the cardioprotective effect of puerarin and support its further development as a therapeutic agent for I/R.
Disulfidptosis-related gene DSTN predicts prognosis and promotes malignant progression in head and neck squamous cell carcinoma.
Peng X, Chen L, Zhang J … +2 more , Yang L, Wu X
Mol Cell Biochem · 2026 Jun · PMID 42101793 · Publisher ↗
Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck tissues. Disulfidptosis is a novel form of programmed cell death caused by disulfide stress, which mainly manifests as...
Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck tissues. Disulfidptosis is a novel form of programmed cell death caused by disulfide stress, which mainly manifests as cytoskeleton protein and F-actin breakdown. In this study, we collected 504 HNSCC patients' data from The Cancer Genome Atlas (TCGA) database and constructed a prognostic disulfidptosis-related gene signature for HNSCC patients. Destrin (DSTN), an actin depolymerizing factor, was considered a reliable prognostic biomarker, with its high expression significantly associated with shorter overall survival (OS) and progression-free survival (PFS). Functional enrichment analysis revealed that DSTN was positively correlated with extracellular matrix (ECM)-related genes, and particularly enriched in ECM degradation pathways and matrix metalloproteinase (MMP) family members, such as MMP10 and MMP3. qPCR and Western blot results showed that knockdown of DSTN inhibited the expression of ECM-related genes MMP10 and MMP3 in HNSCC cells. Tumor immune microenvironment analysis revealed that DSTN was negatively correlated with infiltration levels of various immune cells, immune checkpoints, and tumor mutational burden (TMB). Co-culture experiment of H9 cells with HNSCC cells further demonstrated that DSTN knockdown significantly upregulated the CD274 expression in HNSCC cells. In vitro functional experiments showed that DSTN knockdown effectively inhibited HNSCC cell proliferation and migration, suppressed glucose metabolism, and blocked Wnt/β-catenin signaling pathway activation; additionally, it induced F-actin contraction, triggering disulfidptosis. In vivo xenograft experiments confirmed that DSTN knockdown significantly inhibited HNSCC tumor growth. In conclusion, this study demonstrates that DSTN is a key driver promoting the malignant progression of HNSCC; high DSTN expression indicates poor prognosis, while its downregulation exerts tumor-suppressive effects through multiple mechanisms, including inhibiting the secretion of MMPs, suppressing glucose metabolism, blocking the Wnt/β-catenin signaling pathway, and inducing disulfidptosis.
Inhibition of endothelial S1PR2 preserves blood-brain barrier integrity after traumatic brain injury through activating the PI3K-AKT signaling pathway.
Cheng H, Wang Q, Men Y … +10 more , An Y, Ma B, Dai S, Jing Z, He X, Bao X, Long Y, Yu J, Wu Y, Sun G
Mol Cell Biochem · 2026 Jun · PMID 42101792 · Publisher ↗
Traumatic brain injury (TBI) is a major cause of blood-brain barrier (BBB) disruption and neurological dysfunction, wherein endothelial dysfunction plays a critical pathogenic role. As a member of the G protein-coupled r...
Traumatic brain injury (TBI) is a major cause of blood-brain barrier (BBB) disruption and neurological dysfunction, wherein endothelial dysfunction plays a critical pathogenic role. As a member of the G protein-coupled receptor family, sphingosine-1-phosphate receptor 2 (S1PR2) is known to regulate vascular homeostasis; however, its specific role in protecting the blood-brain barrier following TBI remains unclear. This study aims to elucidate the mechanism by which S1PR2 maintains blood-brain barrier integrity and to evaluate the therapeutic potential of S1PR2 inhibition after TBI. A mouse model of TBI was established using controlled cortical impact, while human umbilical vein endothelial cells (HUVECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic ischemia-reperfusion injury in vitro. We employed shRNA technology to knock down S1PR2 expression and utilized single-cell RNA sequencing (dataset GSE269748) to characterize cell type-specific expression profiles. Endothelial function, blood-brain barrier permeability, inflammatory responses, and cell apoptosis were assessed using tube formation assays, transendothelial electrical resistance (TER) analysis, Western blotting, immunofluorescence, qPCR, ELISA, Evans blue staining, and brain water content measurements. Behavioral tests including open field test and novel object recognition test were used to evaluate the recovery of neurological function. At the same time, the PI3K-AKT pathway was interfered by S1PR2 knockdown mediated by AAV virus and pharmacological inhibitor (JTE-013/LY94002) or activator (Cyn). Single-cell analysis revealed that S1PR2 is specifically expressed in endothelial cells and is significantly upregulated following TBI. In vitro, S1PR2 knockdown counteracted the OGD/R-induced reduction in tube formation capacity and the elevation in transendothelial electrical resistance, and restored the expression of tight junction proteins Occludin and ZO-1. RNA-seq and KEGG enrichment analysis suggested that PI3K-AKT pathway was the key downstream target of S1PR2. In vivo experiments demonstrated that S1PR2 expression peaked at 72 h post-TBI and colocalized with CD31, while the ratios of p-PI3K/PI3K and p-AKT/AKT were markedly reduced. Intervention targeting S1PR2 significantly enhanced locomotor activity and novel object recognition, reduced brain lesion area, suppressed neuronal apoptosis and inflammatory cytokine levels, and restored BBB integrity in TBI mice. Mechanismally, activation of PI3K-AKT pathway could mimic the protective effect of S1PR2 knockdown, whereas inhibition of this pathway negated the improvements in BBB integrity and neurological function induced by S1PR2 knockdown. Endothelial S1PR2 is a critical regulator of vascular homeostasis after TBI. Inhibition of Endothelial S1PR2 preserves blood-brain barrier integrity, mitigates neuroinflammation and apoptosis, and promotes neurological recovery through activation of the PI3K-AKT signaling pathway, thereby offering a promising new strategy for targeted TBI therapy.
Transplantation of Ru265-treated mitochondria enhances the therapeutic impact on skeletal muscle ischemia-reperfusion injury.
Barki S, Wahid F, Khan S … +7 more , Abbasi LT, Rubab Z, Hamza A, Ullah F, Ahsan K, Shehwar D, Alam MR
Mol Cell Biochem · 2026 May · PMID 42081168 · Publisher ↗
Mitochondrial transplantation (MT) is a promising therapeutic approach for the treatment of several pathologies, including ischemia-reperfusion injury (IRI). However, its efficacy remains limited by the high calcium conc...
Mitochondrial transplantation (MT) is a promising therapeutic approach for the treatment of several pathologies, including ischemia-reperfusion injury (IRI). However, its efficacy remains limited by the high calcium concentration of the transplantation milieu. Elevated extracellular calcium induces MCU-mediated matrix calcium overload, leading to the opening of the permeability transition pore and metabolic collapse of the transplanted organelles. We hypothesized that shielding mitochondria from the adverse effects of high calcium using the reversible MCU inhibitor, Ru265, would increase the efficacy of MT therapy. An acute, non-invasive hindlimb skeletal muscle IRI model was established in BALB/c mice using orthodontic rubber bands to mimic peripheral artery disease. Isolated liver mitochondria were treated with Ru265 and evaluated for their responsiveness to calcium using the mitochondrial swelling assay. Mice subjected to hindlimb IRI received either standard MT (Mitochondria alone) or Ru265-treated mitochondria (Mito + Ru), and treatment efficacy was evaluated using various parameters. IRI induced significant changes in mouse body weight, musculoskeletal dysfunction, systemic inflammation, lipid peroxidation, and skeletal muscle damage. While standard MT therapy provided baseline recovery, the Mito + Ru group demonstrated superior outcomes, including significant body weight recovery, reduced infarct size, and attenuated oxidative stress. Thus, reversible shielding of exogenous mitochondria from calcium stress using Ru265 enhances the efficacy of MT therapy in rodent skeletal muscle IRI.
Polarized mitochondrial respiratory chain complexes in synaptic mitochondria induced by plasticity signals.
Wang X, Zhou G, Hu Y … +5 more , Liu K, Zuo C, Yan T, Guan JS, Xie H
Mol Cell Biochem · 2026 May · PMID 42068531 · Publisher ↗
Mitochondria are well established as key supporters of synaptic plasticity, yet the nanoscale spatial distribution of specific mitochondrial membrane proteins during this process remains poorly understood. Using 3D MINFL...
Mitochondria are well established as key supporters of synaptic plasticity, yet the nanoscale spatial distribution of specific mitochondrial membrane proteins during this process remains poorly understood. Using 3D MINFLUX nanoscopy, we investigated their polarized distribution within synapses of cortical neurons undergoing chemical long-term potentiation (cLTP). Upon cLTP induction in DIV17 neurons, we observed an increased mitochondrial occupancy in stimulated synapses. Respiratory complexes of the inner mitochondrial membrane (IMM)-such as COX-IV and SDHA-showed a polarized accumulation near presynaptic sites, as validated by cluster analysis and 3D mapping. By contrast, outer mitochondrial membrane (OMM) proteins, including TOMM20 and VDAC, exhibited no significant polarized distribution. Together, these results demonstrate that cLTP selectively remodels the inner mitochondrial membrane to address localized energy requirements, highlighting the power of 3D MINFLUX for resolving protein organization with subcellular precision.
Exploring the off-label use of liraglutide in the treatment of obesity: a review.
Braga CBA, Segundo JPVA, Filho CAAD
Mol Cell Biochem · 2026 Jun · PMID 42060040 · Publisher ↗
Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, has been used off-label for the treatment of obesity due to its considerable weight-reducing effects. This integrative review evaluated experimental studies in human...
Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, has been used off-label for the treatment of obesity due to its considerable weight-reducing effects. This integrative review evaluated experimental studies in humans in order to explore the pharmacological mechanisms, metabolic effects, and the various clinical responses involved in the use of this drug. The research was conducted in the PubMed database, considering articles written in English and published in the last 10 years, with 9 studies included. The studies demonstrated that liraglutide is effective for weight loss and acts through gastric emptying, modulation of satiety, and influences on brain regions. Additionally, genetic polymorphisms may interfere with the clinical response. Regarding metabolic effects, improvements in glycemia and hepatic steatosis were observed, as well as possible anti-inflammatory action and improvement in blood pressure and lipid profile. The efficacy of liraglutide does not depend on variables such as BMI (Body Mass Index) or age; however, alcohol consumption and proper adherence to treatment may influence clinical outcomes. The main adverse effects, such as nausea and constipation, were well tolerated. Therefore, liraglutide can be considered a promising alternative in the management of obesity, especially in populations with multiple metabolic risk factors.
Elevated placental inflammation as a mediator of adverse outcomes in gestational diabetes mellitus.
Madiwale S, Godhamgaonkar A, Karkhanis A … +7 more , Kasture V, Pisal H, Randhir K, Sundrani D, Wagh G, Gupte S, Joshi S
Mol Cell Biochem · 2026 Apr · PMID 42053876 · Publisher ↗
Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication associated with adverse maternal and neonatal outcomes. This study aims to investigate the expression of key inflammatory markers - tumor necrosis...
Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication associated with adverse maternal and neonatal outcomes. This study aims to investigate the expression of key inflammatory markers - tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-6 (IL-6), and nuclear-factor kappa-light chain of B (NFκB) in the placental tissue of GDM and non-GDM women. Additionally, the study explores associations between these markers and neonatal characteristics, placental dimensions, and resolvins levels. This cross-sectional study included 416 singleton pregnant women, comprising 209 with GDM and 207 non-GDM. Placental protein and mRNA expression levels of TNF-α, IL-10, IL-6, and NFκB were measured using ELISA and RT-qPCR. Associations between resolvins and inflammatory markers were also assessed. Placental protein levels of TNF-α, IL-10, and NFκB, as well as gene expression levels of IL-6, were elevated in the GDM group. Furthermore, TNF-α was negatively associated with major axis, thickness and center and cord insertion. Inflammatory markers were negatively associated with head circumference at birth. A negative association was found between placental resolvin E1 (RvE1) levels and the inflammatory markers IL-10, NFκB, and TNF-α. The study highlights the association between pro-inflammatory and pro-resolving mediators in the placenta, providing insights into GDM and its adverse outcomes.
Squalene attenuates doxorubicin resistance in hepatocellular carcinoma by targeting SIRT6 to inhibit ERK1 deacetylation.
Xiao G, Liu F, Wang Q … +2 more , He B, Fu Y
Mol Cell Biochem · 2026 Jun · PMID 42048041 · Publisher ↗
Hepatocellular carcinoma (HCC), a globally prevalent malignant tumor, faces therapeutic challenges due to chemotherapy resistance. Although squalene has demonstrated anti-tumor and resistance reversal potential, its mech...
Hepatocellular carcinoma (HCC), a globally prevalent malignant tumor, faces therapeutic challenges due to chemotherapy resistance. Although squalene has demonstrated anti-tumor and resistance reversal potential, its mechanism of action in HCC drug resistance remains to be fully elucidated. Doxorubicin (DOX)-resistant HCC cell models were established. The impact of SIRT6 on DOX resistance was assessed using CCK-8, colony formation, flow cytometry, and Western blot of apoptosis-related proteins. The binding between squalene and SIRT6 was verified by molecular docking and cellular thermal shift assay. The effect of SIRT6 on ERK1 deacetylation was predicted bioinformatically and confirmed by co-immunoprecipitation and immunofluorescence. Finally, a nude mouse xenograft model was established to validate that squalene overcomes DOX resistance in HCC by targeting SIRT6 in vivo. SIRT6 knockdown suppressed the viability and proliferation of DOX-resistant cells and enhanced apoptosis. SIRT6 functions by regulating ERK1 deacetylation. SIRT6 inhibition increased ERK1 acetylation and reduced the expression of phosphorylated ERK1/2 (p-ERK1/2). Squalene effectively reversed DOX resistance by targeting SIRT6 to inhibit ERK1 deacetylation in HCC cells. Squalene suppresses DOX resistance by targeting SIRT6 to inhibit ERK1 deacetylation in HCC. The study provides novel molecular insights and identifies a druggable target for HCC therapy.
Study on the pro-inflammatory mechanism mediated by the RANK-SPP1 axis in macrophage immunomodulation during atherosclerosis.
Sun Q, Hu Y, Sun Z … +7 more , Shang M, Li Z, Shen J, Cui Z, Yang J, Ma X, Li M
Mol Cell Biochem · 2026 May · PMID 42048040 · Publisher ↗
Atherosclerosis (AS) is a chronic inflammatory disease driven by macrophages. While the RANK/RANKL signaling axis and SPP1 (osteopontin) are individually known to contribute to vascular inflammation, whether they functio...
Atherosclerosis (AS) is a chronic inflammatory disease driven by macrophages. While the RANK/RANKL signaling axis and SPP1 (osteopontin) are individually known to contribute to vascular inflammation, whether they function within a coordinated regulatory hierarchy in plaque macrophages remains unknown. This study investigates whether RANK defines a pro-inflammatory macrophage subset and whether SPP1 acts as a critical downstream effector within the RANK signaling pathway to promote AS progression. Plaque tissue samples were obtained from databases of atherosclerotic patients, experimental atherosclerotic animal models, and in vitro cell experiments to analyze the role of the RANK molecule and macrophages in atherosclerosis and to investigate its association with disease severity. Single-cell RNA sequencing, histological analysis, co-culture of ox-LDL with macrophages, and gene knockout animal experiments were employed to study the mechanism of RANK high expression on macrophages in atherosclerosis progression. We found that high expression of RANK is closely correlated with the severity of atherosclerosis. Single-cell transcriptomic analysis revealed that RANK⁺ cells are primarily enriched in macrophages, and RANK⁺ macrophages exhibit active metabolic and immune response pathways in AS. Cell communication analysis showed that RANK⁺ macrophages are closely associated with SPP1, with SPP1 being a key gene in RANK⁺ macrophages. Furthermore, the number of RANK⁺/SPP1⁺ macrophages increases with AS progression. Mechanistically, SPP1 is a downstream gene of RANK. RANK promotes AS progression by upregulating SPP1, acting through macrophage immunomodulatory pathways. Knocking out RANK in macrophages suppressed SPP1 expression and inhibited the ability of macrophages to phagocytose ox-LDL. Additionally, inhibiting RANK in mouse and rat AS models similarly suppressed SPP1 expression and reduced plaque formation, thereby delaying AS progression. This study establishes a previously unrecognized RANK-SPP1 signaling axis that functions as a macrophage-autonomous inflammatory amplifier in atherosclerosis. We demonstrate that RANK defines a distinct pro-inflammatory macrophage subset characterized by high metabolic and inflammatory pathway activity. Mechanistically, RANK transcriptionally upregulates SPP1 via the NF-κB pathway, and the accumulation of RANK⁺SPP1⁺ macrophages correlates with disease severity. Pharmacological inhibition of RANK signaling attenuates plaque progression in preclinical models, highlighting this axis as a potential therapeutic target for AS.
Co-translational profiling in the cardiac endothelium in response to LPS-induced inflammation in female mice in vivo: a proof-of-concept approach.
Warren CM, Swaminathan B, Langa P … +7 more , Villa SR, Thompson WC, Chrzanowska M, Kitajewski JK, Solaro RJ, Wolska BM, Goldspink PH
Mol Cell Biochem · 2026 Jun · PMID 42048039 · Full text
Producing functional proteins involves multiple steps during mRNA translation on the ribosomes. However, co-translational regulatory mechanisms remain poorly characterized in intact mammalian systems. As a proof-of-conce...
Producing functional proteins involves multiple steps during mRNA translation on the ribosomes. However, co-translational regulatory mechanisms remain poorly characterized in intact mammalian systems. As a proof-of-concept, we developed a multi-omics approach to investigate endothelial-specific, co-translational regulation by modifying the translating ribosome affinity purification (TRAP) in vivo. We simultaneously co-immunoprecipitated (IP) polysome-associated mRNAs and proteins from the hearts of hemagglutinin-tagged ribosomal protein L22 mice (RiboTag) crossed with inducible endothelial-specific Cdh5CreERT2 mice (RiboTag). To perturb endothelial function, female mice were injected with E. coli lipopolysaccharide (LPS) (6 mg/Kg, i.p., 12 h). Hearts were homogenized, with ~ 10% used for input RNA-Seq and proteomics controls, and the remainder for IP of ribosome-bound polyadenylated mRNA and proteins. Endothelial cell transcripts (pecam1, cdh5) were enriched > 5-fold, while markers characteristic of other cell types were significantly depleted (< 0.05 q-value). We aligned transcriptomic and proteomic datasets (> 1250 overlapping terms) to identify pathways associated with concordant and discordant co-translational regulation. LPS was identified as the upstream regulator of the co-translational dataset that was concordantly regulated. Upregulated mRNAs but not proteins related to glycolysis were discordantly regulated. These findings validate our proof-of-concept multi-omics approach as a predictive platform for identifying disease-relevant pathways regulated at the co-translational level in vivo.
Association between obstructive sleep apnea, high-sensitivity c-reactive protein, and mitral annular calcification: a cross-sectional analysis of 200 adults undergoing routine medical evaluation.
Li J, Feng A, Li Y … +3 more , Fang Z, Zhu Z, Shen L
Mol Cell Biochem · 2026 Jun · PMID 42048038 · Publisher ↗
This study aims to explore the relationship between obstructive sleep apnea (OSA) and mitral annular calcification (MAC), and to assess the role of high-sensitivity C-reactive protein (hs-CRP). A cross-sectional study wa...
This study aims to explore the relationship between obstructive sleep apnea (OSA) and mitral annular calcification (MAC), and to assess the role of high-sensitivity C-reactive protein (hs-CRP). A cross-sectional study was conducted involving 200 individuals who underwent physical examinations at Shanghai Health and Medical Center and received medical services at Zhongda Hospital between January and December 2025. From polysomnography findings, participants were categorized into the OSA group (n = 160) and the non-OSA group (n = 40). All participants underwent transthoracic echocardiography and serum hs-CRP measurement. Statistical analyses were performed using SPSS version 26.0. The OSA group demonstrated significantly higher age, proportion of males, body mass index (BMI), apnea-hypopnea index (AHI), prevalence of MAC (96.3% vs. 2.5%), and hs-CRP levels (2.9 ± 2.7 vs. 1.3 ± 1.2 mg/L) compared to the non-OSA group (p < 0.01). hs-CRP levels increased progressively with OSA severity and MAC severity (trend p < 0.001). Correlation analysis indicated positive associations between AHI and MAC severity (r = 0.680, p < 0.001), as well as between hs-CRP and MAC severity (r = 0.512, p < 0.001). In multiple linear regression analysis, after adjustment for age, sex, BMI, lipid profile, and blood glucose levels, both AHI (β = 0.403, p < 0.001) and hs-CRP (β = 0.286, p < 0.001) remained independent factors positively associated with MAC severity. OSA severity was independently associated with the presence and severity of MAC. Elevated hs-CRP levels, indicative of systemic inflammation, may represent a key mechanistic link between OSA and MAC.
USP7-stabilized CEBPB promotes HpSCC progression by upregulating IL6 to activate the JAK2/STAT3 signaling.
Li H, Fan R, Qu Y … +5 more , Shao Y, Bai Y, Xu C, Hu J, Zhang X
Mol Cell Biochem · 2026 Jun · PMID 42048037 · Publisher ↗
BACKGROUND: CCAAT/enhancer-binding protein B (CEBPB) has been reported as a transcription factor implicated in the occurrence and development of various human tumors. However, its role and mechanism in hypopharyngeal squ...
BACKGROUND: CCAAT/enhancer-binding protein B (CEBPB) has been reported as a transcription factor implicated in the occurrence and development of various human tumors. However, its role and mechanism in hypopharyngeal squamous cell carcinoma (HpSCC) remain unclear. METHODS: qRT-PCR, western blot, and immunohistochemistry assays were used for mRNA or protein expression in HpSCC tissus or cells. HpSCC cell phenotypes were evaluated using colony formation, EdU, wound healing, and transwell assays. The role of CEBPB in HpSCC tumorigenesis was also investigated by establishing xenograft model in mice. Interaction between CEBPB and ubiquitin-specific peptidase 7 (USP7) was confirmed using co-immunoprecipitation (Co-IP), cycloheximide (CHX) chase, and deubiquitination assays. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were employed to determine the transcription regulation of CEBPB on IL-6. RESULTS: Higher CEBPB expression was found in HpSCC tissues and represented a worse prognosis. Knockdown of CEBPB inhibited HpSCC cell proliferation, migration, invasion, and EMT, while overexpression of CEBPB displayed the opposite trend. USP7 stabilized CEBPB protein by its deubiquitination activity. CEBPB binds to the promoter of IL-6 to increase its transcription, thus activating the JAK2/STAT3 signaling pathway. Furthermore, USP7 could promote IL-6 expression through CEBPB. Functionally, restoration of CEBPB expression reversed the anti-cancer effect of USP7 depletion in HpSCC. Moreover, the inhibitory effect of HpSCC progression mediated by CEBPB knockdown was abated upon IL-6 upregulation. CONCLUSION: Our finding reveals a novel USP7/CEBPB/IL-6/JAK2/STAT3 axis in regulating HpSCC progression, targeting this pathway might be a valuable strategy for HpSCC therapy.
Cannabidiol potentiates olaparib-induced cytotoxicity through cell cycle arrest and DNA damage modulation in breast cancer cells.
Deniz C, Yüksel B, Cebeci E … +1 more , Şahin F
Mol Cell Biochem · 2026 Jun · PMID 42048036 · Full text
Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive nature and limited treatment options, while therapeutic resistance in estrogen receptor-positive (ER+) breast cancer continues...
Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive nature and limited treatment options, while therapeutic resistance in estrogen receptor-positive (ER+) breast cancer continues to limit treatment efficacy. Although olaparib is primarily effective in BRCA-mutated cancers, its activity in BRCA-wild type (BRCA-wt) tumors is limited. Therefore, this study aimed to investigate whether cannabidiol (CBD) can enhance the response of BRCA-wt breast cancer cells to PARP inhibition. The effects of olaparib (OLAP) and CBD, alone and in combination, were evaluated in MDA-MB-231 (TNBC) and MCF-7 (ER+) cell lines using comprehensive two-dimensional (2D) mechanistic analyses and three-dimensional (3D) spheroid models, including HCC-70 cells to extend TNBC validation. The results demonstrate that combined OLAP and CBD treatment enhanced cytotoxic effects compared to single treatments, with more pronounced responses observed in 3D spheroid models, particularly in TNBC models. Flow cytometry and caspase 3/7 assays indicated increased apoptosis and G2/M phase arrest following combination treatment. Gene expression analysis revealed downregulation of key DNA damage response and cell cycle-related genes (ATM, ATR, BRCA1/2, RAD51, and CDK1/2/4/6), supporting a role for cell cycle arrest and DNA damage modulation in mediating these effects. Functional assays showed reduced colony formation and migratory capacity, although these effects may reflect both cytotoxic and cytostatic responses under the selected experimental conditions. Overall, these findings suggest that CBD may enhance the efficacy of olaparib in BRCA-wt breast cancer models and highlight its potential as a combinational therapeutic strategy in breast cancer treatment.
HIRA promotes osteogenic differentiation of BMSCs and ameliorates osteoporosis by mediating M2 polarization of macrophages through the YAP1/β-catenin pathway.
Hou Y, Li Y, Liu K … +3 more , Zhai G, Liang X, Zheng J
Mol Cell Biochem · 2026 Jun · PMID 42048035 · Publisher ↗
Impaired macrophage polarization is a key factor exacerbating osteoporosis (OP), influencing bone metabolism via modulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Histone cell cycle...
Impaired macrophage polarization is a key factor exacerbating osteoporosis (OP), influencing bone metabolism via modulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Histone cell cycle regulator (HIRA), an epigenetic regulator, is downregulated in OP. However, its role in modulating macrophage polarization and BMSCs osteogenic differentiation remains unclear. Bone marrow-derived macrophages (BMDMs) and BMSCs were extracted from the bone marrow of SD rats, and identified using staining and flow cytometry. An ovariectomized (OVX) mouse model was established, and HIRA protein was detected via Western blot. A co-culture system of BMDMs and BMSCs was established, and BMDMs were transfected with an HIRA overexpression plasmid. Cytokine levels were measured by ELISA kits, bone structure was assessed via micro-CT, and histopathological staining evaluated femoral tissue pathology, calcium deposition, and osteoclast counts. The levels of proteins associated with osteogenic differentiation, osteoclast differentiation, macrophage polarization, and the YAP1/β-catenin pathway were detected using Western blot. HIRA is downregulated in BMSCs treated with dexamethasone and in the femoral tissues of OVX mice. Overexpression of HIRA effectively raised M2 polarization markers and reduced M1 polarization markers in BMDMs, and promoted BMSCs osteogenic differentiation. Following HIRA overexpression in OVX mice, femoral tissue damage was significantly reduced, osteoclast numbers decreased, and bone metabolic imbalance improved. Furthermore, HIRA overexpression also activated the YAP1/β-catenin axis in the femoral tissue of OVX mice, thereby suppressing bone loss and promoting macrophage M2 polarization. HIRA promotes M2 polarization of macrophages by activating the YAP1/β-catenin pathway, thereby enhancing BMSC osteogenic differentiation and ultimately reducing bone loss in OVX mice.
A cardiac fibrosis specific circRNA_006640 sponges miR-7648-3p and miR-185-3p to synergistically up-regulate CTGF.
Yang L, He X, Luo K … +7 more , Zhang X, Li H, Zhou W, Pang J, Zhang M, Zhou Z, Ren M
Mol Cell Biochem · 2026 Jun · PMID 42048034 · Full text
Cardiac fibrosis is a critical pathological feature in nearly all forms of heart disease and contributes to heart failure. However, existing diagnostic and therapeutic approaches are insufficient for detecting fibrosis o...
Cardiac fibrosis is a critical pathological feature in nearly all forms of heart disease and contributes to heart failure. However, existing diagnostic and therapeutic approaches are insufficient for detecting fibrosis or targeting conventional pathways. Further molecular investigations are urgently needed to develop effective treatments. Circular RNAs (circRNAs), distinguished by their stability and regulatory roles, show significant potential. CircRNA_006640 was substantially upregulated in left ventricular tissues of male mice subjected to transverse aortic constriction, as well as in blood samples. Gain- and loss-of-function studies confirmed that circRNA_006640 promoted proliferation and phenotypic transformation in mouse cardiac fibroblasts. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting demonstrated that circRNA_006640 suppressed miR-7648-3p and miR-185-3p, which in turn inhibited connective tissue growth factor (CTGF). Furthermore, there was a synergistic effect between miR-7648-3p and miR-185-3p to enhance the suppression of CTGF. In vivo, circRNA_006640 markedly exacerbated cardiac fibrosis. Knockdown of circRNA_006640 using small interfering RNA effectively mitigated cardiac fibrosis and preserved cardiac function, indicating therapeutic potential for antifibrotic strategies. CircRNA_006640 acts as a novel upstream regulator of CTGF, exacerbating cardiac fibrosis by sponging miR-7648-3p and miR-185-3p. The synergistic interaction between miR-7648-3p and miR-185-3p strengthens the profibrotic effect. Targeting CircRNA_006640 may hold promising therapeutic potential for cardiac fibrosis.
LNA GapmeR silencing of KRAS G12V impairs growth and function in SW480 cells.
Khudeir JF, Tlili A
Mol Cell Biochem · 2026 Jun · PMID 42048033 · Publisher ↗
Activating mutations in the KRAS oncogene, particularly the G12V substitution, are key drivers of tumorigenesis and therapeutic resistance across multiple cancer types. However, direct pharmacological inhibition of mutan...
Activating mutations in the KRAS oncogene, particularly the G12V substitution, are key drivers of tumorigenesis and therapeutic resistance across multiple cancer types. However, direct pharmacological inhibition of mutant KRAS has remained a major clinical challenge due to its structural and biochemical properties. In this study, we employed a chemically modified locked nucleic acid (LNA) GapmeR antisense oligonucleotide specifically designed to target the KRAS G12V transcript. The SW480 cell line was used as a representative in vitro model. Assays conducted were Quantitative RT-PCR, luciferase reporter assay using a KRAS representative construct, MTT assay, wound-healing assay, Annexin V-FITC apoptosis assay, and cell cycle distribution. RT-qPCR confirmed a marked reduction in KRAS mRNA levels. Luciferase reporter assay provided further evidence of GapmeR-mediated suppression at the transcript level. MTT revealed a robust cytotoxic effect at 100 nM, sufficient to induce significant cancer cell death while sparing normal cells. Scratch assay demonstrated increased scratch area, along with morphological changes. Apoptosis assay revealed a pronounced induction of late apoptosis and necrosis. Cell cycle analysis indicated disruption of the cell cycle. Our findings establish evidence that transcript level targeting of KRAS G12V using GapmeRs is associated with functional alterations in SW480 cells, warranting further validation in additional cancer models and in vivo studies.
The Bidens pilosa extract Jacein alleviates hypertension by restoring mitochondrial dynamic balance through modulating the FAM210A/OPA1 signaling pathway.
Yang T, Lu X, Chen Q
Mol Cell Biochem · 2026 Jun · PMID 42048032 · Publisher ↗
This study aimed to investigate the mechanism by which Jacein, an extract from Bidens pilosa, alleviates hypertension through regulating mitochondrial dynamics via the FAM210A/OPA1 signaling pathway. Methods For in vitro...
This study aimed to investigate the mechanism by which Jacein, an extract from Bidens pilosa, alleviates hypertension through regulating mitochondrial dynamics via the FAM210A/OPA1 signaling pathway. Methods For in vitro experiments, rat aortic vascular smooth muscle cells (VSMCs) were divided into 6 groups. Control group was cultured under normal conditions. Model group was treated with 1 µM angiotensin II (Ang II) for 24 h. Positive control group received 0.1 µM valsartan on the basis of the model group for 24 h. Jacein low/medium/high dose groups were treated with 10/20/40 µM Jacein respectively on the basis of the model group for 24 h. Cell viability, ATP levels, reactive oxygen species (ROS) levels, and mitochondrial membrane potential were assessed. Mitochondrial morphology was evaluated using transmission electron microscopy. mRNA and protein expression levels were analyzed using qPCR, WB, and co-immunoprecipitation. For in vivo experiments, ten Wistar-Kyoto rats served as controls and fifty spontaneously hypertensive rats (SHRs) were randomly divided into 5 groups. Model group received intragastric administration of normal saline. Positive control group received 100 mg/kg/d valsartan. Jacein low/medium/high dose groups received 50/100/150 mg/kg/d Jacein respectively for 28 d. Blood pressure was measured before euthanasia, followed by tissue collection for analysis of mitochondrial ultrastructure, cell apoptosis, ATP levels, and ROS levels. An additional ten SHRs were used in antagonist experiments with weekly intravenous injections of 5 nmol/kg OPA1 inhibitor MYLS22. In vitro, Ang II treatment significantly reduced cell viability, mitochondrial membrane potential, and ATP content, while significantly increasing ROS levels and mitochondrial fragmentation (P < 0.001). Jacein treatment dose-dependently reversed these effects (P < 0.001). Jacein also upregulated FAM210A, L-OPA1, and MFN2 expression, downregulated DRP1, S-OPA1, and FIS1 expression, and enhanced the interaction between FAM210A and OPA1 (P < 0.05). In vivo, Jacein exhibited dose-dependent blood pressure-lowering effects in SHR rats, while improving mitochondrial ultrastructure, reducing cell apoptosis, increasing ATP content, and lowering ROS levels (P < 0.01). The antagonist experiment showed that OPA1 inhibition significantly weakened Jacein’s beneficial effects on blood pressure, mitochondrial ultrastructure, cell apoptosis, and the interaction between FAM210A/OPA1 (P < 0.01). This study elucidates the mechanism by which Jacein alleviates hypertension by improving mitochondrial dynamics, which is partially associated with the regulation of the FAM210A/OPA1 signaling pathway.
The inflammatory-autophagy-NETs axis in renal fibrosis: mechanistic crosstalk and pathological feed-forward amplification loops.
Chen H, Lin Y, Guo C … +1 more , Li F
Mol Cell Biochem · 2026 Apr · PMID 42048031 · Publisher ↗
A frequent final step in the development of chronic kidney disease is renal fibrosis, which involves a complex molecular network made up of innate immune effectors, cell death, and immunological inflammation. The interac...
A frequent final step in the development of chronic kidney disease is renal fibrosis, which involves a complex molecular network made up of innate immune effectors, cell death, and immunological inflammation. The interaction of three fundamental mechanisms-autophagy/ferroptosis, neutrophil extracellular traps, and the immune-inflammatory microenvironment-is the main topic of this review. M1 macrophages initiate inflammation at the immune-inflammatory level in the early phases of damage, whereas M2 macrophages directly encourage fibrosis in the later stages by secreting molecules like TGF-β. Their polarization process is carefully controlled by signaling pathways like HIF-1α and NF-κB. A new mediator between acute and chronic injuries, neutrophil extracellular traps directly damage tissues by releasing toxic components and can activate macrophages and fibroblasts. Ferroptosis damages renal tubular epithelial cells through iron dependent lipid peroxidation, and its upstream iron autophagy becomes a crucial bridge connecting autophagy and ferroptosis through NCOA4 mediated ferritin degradation. These processes work together to create a well-coordinated network: ferroptosis-released damage compounds trigger NLRP3 inflammasomes; neutrophil extracellular traps encourage M2 macrophage polarization; and the inflammatory agent TGF-β can increase the expression of genes linked to autophagy. Together, these interactions create a vicious cycle of fibrosis, inflammation, and cell death. A thorough examination of this molecular network will offer fresh theoretical underpinnings and therapeutic guidance for the creation of multi-target synergistic treatment approaches.
SENP1 regulates the malignant activities of osteosarcoma cells and antitumor immunity via the cGAS-STING signaling.
Lyu S, Wu H, Wei Z … +1 more , Xie J
Mol Cell Biochem · 2026 Jun · PMID 42048030 · Publisher ↗
Osteosarcoma is an aggressive bone malignancy with poor prognosis. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical in anti-tumor immunity, its regulation in osteosarcoma rema...
Osteosarcoma is an aggressive bone malignancy with poor prognosis. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical in anti-tumor immunity, its regulation in osteosarcoma remains unclear. Through UALCAN database screening, we identified elevated SUMO-specific protease 1 (SENP1) expression in sarcoma tissues, but whether it affects STING pathway remains unclear. Although other SENP family members (such as SENP2 and SENP6) have been implicated in immune regulation, their direct role in STING deSUMOylation within the osteosarcoma is limited. Herein, we explore how SENP1 (SUMO-specific protease 1) influences osteosarcoma progression and anti-tumor immunity by modulating the cGAS-STING pathway. SENP1 expression was preliminary analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) webserver and The Cancer Genome Atlas (TCGA) dataset, and further verified by western blot. Cell malignant activities were determined by functional assays Specific protein expressions were analyzed by western blot and immunohistochemistry. The mechanism of SENP1 regulating cGAS-STING pathway was validated by immunoprecipitation (IP) and co-immunoprecipitation (Co-IP) assays. In vivo experiments were finally conducted to verify the function of SENP1. The expression of SENP1 was markedly elevated in osteosarcoma cell lines. SENP1 silencing markedly suppressed the proliferation, migration, and invasion of U2OS and MG63 cells. Additionally, SENP1 silencing upregulated cGAS and STING protein levels. Mechanistically, SENP1 interacted with cGAS and regulated its SUMOylation status. The inhibitory effects of SENP1 knockdown on osteosarcoma cell proliferation, migration, and invasion, as well as its promotive effects on CD8+ T cell migration and the secretion of cytotoxic factors (IFN-γ, GZMB, and IL-2), were significantly reversed by concomitant cGAS depletion. In vivo, SENP1 deficiency inhibited tumor growth in xenograft models, activated the cGAS-STING pathway, and enhanced CD8+ T cell-mediated cytotoxicity. SENP1 silencing restrains osteosarcoma cell proliferation, migration, invasion and facilitates anti-tumor immunity via activation of the cGAS-STING signaling.
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