Molecular And Cellular Probes[JOURNAL]
Sun
200 papers
The CXCL9-CXCR3 axis mediates tumor progression and immune checkpoint regulation in colorectal cancer.
Yuan Y, Peng Z, Yucheng S
Mol Cell Probes · 2026 Jun · PMID 42323172 · Publisher ↗
Tumor-immune interactions in the cancer microenvironment have a major influence on the development of colorectal cancer (CRC), as well as immune evasion by the CRC tumor. Chemokine CXCL9 (which signals through the CXCR3...
Tumor-immune interactions in the cancer microenvironment have a major influence on the development of colorectal cancer (CRC), as well as immune evasion by the CRC tumor. Chemokine CXCL9 (which signals through the CXCR3 receptor) has been implicated in the immune recruitment of cells and progression of tumors; however, the role of CXCL9 in CRC is poorly understood. To explore the mechanistic role of CXCL9 in CRC cell proliferation, migration, invasion, survival, and immune modulation, we utilized CRC cell lines HCT116 and HT-29. Knocking down CXCL9 expression using siRNA decreased CRC cell proliferation, EdU incorporation, clonogenic survival, and anchorage-independent growth. The restoration of CXCL9 expression partially reversed these observations. In migration and invasion assays, CXCL9 increased motility and epithelial-mesenchymal transition (EMT) of CRC cells via the regulation of E-cadherin, N-cadherin, and vimentin expression. Silencing CXCL9 expression (due to the CXCL9 siRNA) resulted in increased apoptosis and G0/G1 cell cycle arrest, whereas restoring CXCL9 expression allowed CRC cells to transition to S-phase. Mechanistically, CXCL9 maintained redox homeostasis by preventing accumulation of reactive oxygen species (ROS), and activating pro-survival signaling pathways (AKT, ERK1/2, and NF-κB). Importantly, CXCL9 positively regulated immune checkpoint molecules (PD-L1 and IDO1) at both mRNA and protein levels. In co-culture experiments, CXCL9 promoted CD8 T-cell chemotaxis through CXCR3 and enhanced T-cell-mediated cytotoxicity, effector molecule expression, and pro-inflammatory cytokine secretion under the tested in vitro conditions. Together, these in vitro findings suggest that CXCL9 contributes to CRC cell proliferation, migration, invasion, redox regulation, immune checkpoint-associated signaling, and CD8 T cell responses in simplified co-culture models. The novelty of this study lies in the combined evaluation of tumor-cell phenotypes, PD-L1/IDO1-associated signaling, and CD8 T cell responses within the same CXCL9-modulated CRC cell-line system. Further validation using patient-derived samples, in vivo models, and clinically annotated cohorts is required before broader conclusions regarding the CRC tumor microenvironment or therapeutic targeting can be made.
Harnessing serum exosomal snoRNAs: A novel liquid biopsy approach for NSCLC diagnosis.
Hong J, Wang Y, Wu T … +2 more , Zhang Z, Wang K
Mol Cell Probes · 2026 Jun · PMID 42309446 · Publisher ↗
BACKGROUND: The low early diagnostic efficacy of non-small cell lung cancer (NSCLC) is a key contributor to its high mortality rate, and small nucleolar RNAs (snoRNAs) in serum exosomes can serve as a beneficial liquid b...
BACKGROUND: The low early diagnostic efficacy of non-small cell lung cancer (NSCLC) is a key contributor to its high mortality rate, and small nucleolar RNAs (snoRNAs) in serum exosomes can serve as a beneficial liquid biopsy approach for the early diagnosis of NSCLC. METHODS: Exosomes were isolated from collected serum; their morphology was imaged using transmission electron microscopy (TEM); particle size was measured using a particle size analyzer; and the expression of exosomal membrane proteins was identified using Western blot. Gene chips were used to screen for differentially expressed snoRNAs in exosomes, which were further validated by quantitative PCR (qPCR). The area under the receiver operating characteristic (ROC) curve (AUC) was used to estimate their diagnostic performance for NSCLC. Their biological functions in NSCLC were evaluated using an in vitro study. RESULTS: A series of exosome characterization experiments confirmed successful exosome extraction. Microarray and qPCR analyses revealed that serum exosomal snoRNAs (AC092799.1-201 and AC009408.1-201) were significantly upregulated in individuals with NSCLC. When combined with CEA and CYFRA21-1, these two exosomal snoRNAs achieved diagnostic efficacy of 0.948 and early diagnostic efficacy of 0.917. Cell experiments confirmed that AC092799.1-201 is related to rapid proliferation and high invasiveness of tumor cells. CONCLUSION: Exosomal snoRNAs AC092799.1-201 and AC009408.1-201, merged with CEA and CYFRA21-1, can serve as a novel liquid biopsy approach for the early diagnosis of NSCLC.
Exosomes in celiac disease: From pathogenesis to diagnostic and therapeutic potential.
Lahouty M, Mobayen G, Ghasemian M … +8 more , Lameh EA, Ojaroodi AF, Dastbaz M, Fathzadeh S, Shoaran M, Alizadeh F, Oskouie SA, Aghaei R
Mol Cell Probes · 2026 Aug · PMID 42296831 · Publisher ↗
Celiac disease (CD) is a prototypical example of gluten-induced enteropathy characterized by a strong breakdown of mucosal tolerance. However, the spatial processes underlying intercellular communication across the epith...
Celiac disease (CD) is a prototypical example of gluten-induced enteropathy characterized by a strong breakdown of mucosal tolerance. However, the spatial processes underlying intercellular communication across the epithelial-lamina propria barrier remain poorly known. Exosomes have evolved to be useful orchestrators of this autoinflammatory cascade. In contrast to their passive metabolic by-product role, gut-derived exosomes functionally mediate the non-canonical presentation of deamidated gliadin peptides and disease-associated HLA-DQ complexes, which directly prime pathogenic CD4 T cells independently of conventional cellular synaptic interaction. At the same time, dysregulated exosomal microRNA (miRNA) signatures undermine tight junction integrity and promote pro-inflammatory signaling loops systemically, providing a probable mechanistic link to extra-intestinal symptoms. In this review, the dual role of exosomes as pathogenic propagation vectors and real-time liquid biopsies in CD will be critically discussed.
MYLIP-dependent ubiquitination and degradation of LDLR in acute myeloid leukemia and MAPK signaling.
Liu L, Zhong L, Chen S … +8 more , Ke Z, Zhao Y, Wan P, Zhang Y, Liao Y, Deng Y, Xu T, Liu B
Mol Cell Probes · 2026 Aug · PMID 42235836 · Publisher ↗
Acute myeloid leukemia (AML) is a hematologic malignancy that necessitates the identification of new therapeutic targets. Recently, the low-density lipoprotein receptor (LDLR) has been linked to an unfavorable prognosis...
Acute myeloid leukemia (AML) is a hematologic malignancy that necessitates the identification of new therapeutic targets. Recently, the low-density lipoprotein receptor (LDLR) has been linked to an unfavorable prognosis in AML. LDLR plays a crucial role in various signaling pathways, including the MAPK signaling pathway. Our data show high LDLR expression in the AML cell lines THP-1 and NB4. Knockdown of LDLR using shRNA reduced AML cell proliferation, induced apoptosis, and led to S-phase cell accumulation, accompanied by modulation of the MAPK pathway. Additionally, myosin regulatory light chain-interacting protein (MYLIP) is expressed at low levels in AML and regulates LDLR. Overexpression of MYLIP downregulated LDLR expression, accompanied by an influence on the MAPK signaling pathway. Functionally, MYLIP overexpression decreased AML cell proliferation, increased apoptosis, and potentially delayed S-phase progression. These findings suggest that MYLIP and LDLR may regulate AML cell expansion, potentially through effects on the MAPK pathway. Furthermore, the p38-MAPK activator PCS reversed the inhibitory effect of LDLR knockdown and MYLIP overexpression on cell proliferation. Consequently, targeting LDLR could be a promising approach for AML treatment.
The role of RNA modifications in the pathological mechanisms and therapeutic targeting of multiple myeloma.
Chen H, Ren H, Wang X … +7 more , Liu C, Jiang L, Zang S, Liu T, Wang S, Huang W, Zhou L
Mol Cell Probes · 2026 Aug · PMID 42177998 · Publisher ↗
Multiple myeloma (MM) remains largely incurable despite major therapeutic advances, underscoring the need to define novel pathogenic mechanisms and druggable targets. Epitranscriptomic dysregulation, encompassing reversi...
Multiple myeloma (MM) remains largely incurable despite major therapeutic advances, underscoring the need to define novel pathogenic mechanisms and druggable targets. Epitranscriptomic dysregulation, encompassing reversible chemical modifications on RNA, has emerged as a post-transcriptional regulatory layer that may contribute to MM biology. This focused review discusses the emerging roles of major RNA modifications and their regulators in MM pathogenesis, bone disease, drug resistance, and immune escape. We summarize representative experimental and translational studies on RNA-modifying enzymes, non-coding RNAs, and the bone marrow microenvironment, with emphasis on mechanisms directly validated in MM. Evidence derived from AML, solid tumors, or pan-cancer analyses is discussed as hypothesis-generating and requiring MM-specific validation. We summarize MM-supported evidence that m6A demethylases such as FTO and ALKBH5, as well as writers such as METTL3 and NSUN2, may regulate the stability and translation of disease-relevant transcripts. We also discuss emerging cross-cancer data on the m7G writer METTL1 as a hypothesis-generating framework that requires MM-specific validation. We delineate how RNA modification-dependent non-coding RNA networks and extracellular vesicle cargo remodel osteoclast and osteoblast function, linking the epitranscriptome to osteolytic bone disease. We further describe RNA modification-driven drug resistance circuits and immune escape pathways involving FTO, METTL3, H19, MALAT1, YTHDF1, and m5C-defined molecular subtypes. Finally, we summarize current epitranscriptomic therapeutic strategies, including small molecule inhibitors of writers, erasers, and readers, RNA-based therapeutics targeting pathogenic non-coding RNAs, and RNA modification-derived prognostic signatures for risk stratification. Collectively, this review discusses RNA-modification machinery as a potentially actionable regulatory layer in MM and outlines key challenges for clinical translation.
First experiences in a US clinical laboratory with Oncomine Dx Express Test: Evaluation in formalin-fixed paraffin-embedded tissues.
Weaver A, Diercks A, Corral A … +11 more , Sowada M, Cotten S, Stephen A, Halpin H, D'Alessio B, Rill K, Longshore E, Jackson L, Tomazin H, Eller KA, Pestano GA
Mol Cell Probes · 2026 Aug · PMID 42176872 · Publisher ↗
Formalin-fixed paraffin-embedded (FFPE) tissues are among the most commonly preserved specimen types in pathology. Clinical-grade next-generation sequencing (NGS) tests require extensive method development including nucl...
Formalin-fixed paraffin-embedded (FFPE) tissues are among the most commonly preserved specimen types in pathology. Clinical-grade next-generation sequencing (NGS) tests require extensive method development including nucleic acid extraction, analytic and clinical validation, and independent laboratory verification studies. The recently FDA-approved Oncomine Dx Express Test (ODxET) is an in vitro diagnostic (IVD) amplicon-based NGS test designed for clinical testing. This study evaluated clinical accuracy of the test in an external laboratory from the manufacturer and using an independent reference assay. We assessed 48 serially sectioned FFPE tissue from 13 diverse tumor types using ODxET on the Genexus Integrated System as compared to a reference hybrid capture NGS panel processed at an independent laboratory. Discrepant findings were confirmed with either a validated amplicon-based NGS panel, or with droplet digital polymerase chain reaction (ddPCR). Overall concordance was 98% at the variant level (n = 89/91) and 96% at the sample level (n = 45/47), with VAFs ranging from 0.37 to 87.51%. Transfer of ODxET into the clinical laboratory was executed following the current guidance from the CAP organization. Standardization of procedures, optimization of NGS assays, and harmonization of bioinformatics pipelines critically improved the inter-laboratory comparability of genomic profiling from FFPE tissue samples and allowed for rapid integration into the clinical laboratory.
Targeting DNMT1 restores PTEN expression in colorectal cancer cells.
El Nobey MA, Shaikh Omar AM, Zari A … +8 more , Alharthi A, Alghamdi MA, Althubaiti EH, Al-Shaeri MA, Bakhsh T, El Hamidy SM, Batawi AH, Hassan A
Mol Cell Probes · 2026 Aug · PMID 42173412 · Publisher ↗
Epigenetic silencing of tumor suppressor genes (TSGs) is a key driver of colorectal cancer (CRC) progression, with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) frequently inactivated through promoter hy...
Epigenetic silencing of tumor suppressor genes (TSGs) is a key driver of colorectal cancer (CRC) progression, with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) frequently inactivated through promoter hypermethylation. This study explored the association between DNA methyltransferase 1 (DNMT1) suppression, PTEN reactivation, and miR-29a-3p modulation following 5-aza-2'-deoxycytidine (5-aza-dC) treatment in CRC cell models. Bioinformatic analyses revealed DNMT1 overexpression, increased PTEN promoter methylation, and a potential regulatory network associated with miR-29a-3p. In vitro, HCT116 and SW620 cells treated with 5-aza-dC exhibited dose-dependent reductions in cell viability, with IC values of 12.38 ± 0.98 μM and 10.04 ± 0.98 μM, respectively. Treatment with 5-aza-dC induced significant PTEN re-expression and DNMT1 downregulation at both the mRNA and protein levels. Methylation-specific PCR (MSP-PCR) suggested reduced PTEN promoter methylation following treatment. Additionally, miR-29a-3p expression was significantly upregulated. These findings suggest that 5-aza-dC restores PTEN expression in association with DNMT1 suppression and PTEN promoter demethylation, while miR-29a-3p upregulation may reflect an associated epigenetic response requiring further mechanistic validation.
Phellinus igniarius targets HIF1A to regulate HK2 and inhibit metabolic reprogramming in acute myeloid leukemia.
Li Z, Tan Y, Xie Z … +4 more , Su G, Yao W, Liu G, Li J
Mol Cell Probes · 2026 Aug · PMID 42142634 · Publisher ↗
BACKGROUND: Phellinus igniarius is a medicinal fungus with anti-cancer activity. Its role in solid tumors has been widely reported, but the mechanism of action on hematological malignancies, especially acute myeloid leuk...
BACKGROUND: Phellinus igniarius is a medicinal fungus with anti-cancer activity. Its role in solid tumors has been widely reported, but the mechanism of action on hematological malignancies, especially acute myeloid leukemia (AML), remains unclear. This study aims to explore the molecular mechanism by which Phellinus igniarius inhibits AML. METHOD: The effects of Phellinus igniarius on the proliferation, migration and apoptosis of HL60 cells were detected by CCK-8, transwell and flow cytometry respectively. The expression and metabolic activity of glycolytic-related proteins were analyzed by Western blot, extracellular acidification rate (ECAR) detection and Enzyme-Linked Immunosorbent Assays (ELISA). The nude mouse transplanted tumor model was established to observe the inhibitory effect of Phellinus igniarius on tumor growth, and the proliferation and apoptosis in vivo were analyzed by Ki67 and TUNEL staining. RESULT: Phellinus igniarius can significantly inhibit the progression of AML both in vivo and in vitro, and down-regulate the expression of key glycolytic enzymes (PGK1, PKM2, GLUT1). The active ingredient ergotamine of Phellinus igniarius and its key target HIF1A were screened out by network pharmacology and molecular docking. Mechanism studies have shown that Phellinus igniarius blocks the transcriptional activation of glycolysis by inhibiting the binding of HIF1A to the HK2 promoter. CONCLUSION: This study reveals that Phellinus igniarius inhibits AML metabolic reprogramming by targeting the HIF1A-HK2 axis, providing a new potential strategy for AML treatment.
ZMIZ1 promotes PAX6 ubiquitination through SMAD3 to drive the malignant progression of acute myeloid leukemia.
Zhou L, Li J, Wang M … +1 more , Geng Y
Mol Cell Probes · 2026 Jun · PMID 41951061 · Publisher ↗
Previous research has indicated that Zinc finger MIZ domain-containing protein 1 (ZMIZ1) was elevated in patients with acute myeloid leukemia (AML); however, the pathological mechanisms underlying ZMIZ1 up-regulation in...
Previous research has indicated that Zinc finger MIZ domain-containing protein 1 (ZMIZ1) was elevated in patients with acute myeloid leukemia (AML); however, the pathological mechanisms underlying ZMIZ1 up-regulation in AML remain unclear. The expression levels of the target proteins, PAX6 ubiquitination modifications, and protein stability were evaluated by Western blot. The effects of regulating ZMIZ1 expression on the growth of AML cells were detected through in vitro and in vivo experiments. The regulatory effects of ZMIZ1 on SMAD3 and PAX6, as well as rescue experiments, were conducted in HL60 cells. In this study, we found that ZMIZ1 and SMAD3 were upregulated in patients with AML, while PAX6 was downregulated. Overexpression of ZMIZ1 significantly promoted HL60 cell growth, while inhibiting cell apoptosis. Consistent with these observations, up-regulation of ZMIZ1 markedly promoted tumor cell growth in nude mice, manifested as increased tumor volume and weight, as well as enhanced tumor cell proliferation. However, ZMIZ1 down-regulation had opposite effects both in vitro and in vivo. Mechanistically, PAX6 is a downstream regulatory factor of ZMIZ1, and its ubiquitination at the K53 position is regulated by ZMIZ1. SMAD3 acts as a bridge to mediate the ubiquitination modification of ZMIZ1 on PAX6. More importantly, PAX6 up-regulation suppressed cell growth induced by ZMIZ1 or SMAD3 overexpression. In conclusion, our findings suggest that targeting ZMIZ1 or overexpressing PAX6 serve as a therapeutic strategy for AML.
Granulocyte-macrophage colony-stimulating factor at work: Promoting vascular maturation for accelerated wound healing.
Ying W, Wang S, Sun P … +2 more , Chen J, Cai H
Mol Cell Probes · 2026 Jun · PMID 41833758 · Publisher ↗
BACKGROUND: Wound healing is a complex biological process involving vascular remodeling and tissue repair. However, the mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates vascular ma...
BACKGROUND: Wound healing is a complex biological process involving vascular remodeling and tissue repair. However, the mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates vascular maturation during wound healing remains unclear. This study aims to investigate the biological mechanism by which GM-CSF promotes vascular maturation and enhances wound repair. METHODS: Human dermal microvascular endothelial cells (ECs) and human brain vascular pericytes (PCs) were cultured separately or in co-culture and treated with various concentrations of GM-CSF. Cell proliferation and migration were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan and Transwell assays. Tube formation assays were performed to evaluate angiogenic potential. The expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot. Endothelial permeability was analyzed using fluorescein isothiocyanate (FITC)-dextran staining. The expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) was assessed by immunofluorescence. RESULTS: GM-CSF substantially raised EC and PC proliferation and migration in a dose-dependent manner, with more pronounced effects observed in co-culture conditions. GM-CSF grew VEGF and Ang-1 in PCs and enhanced tube formation and barrier integrity in both mono- and co-cultured ECs. Furthermore, GM-CSF-stimulated PC-conditioned medium induced the upregulation of PECAM-1 in ECs. CONCLUSION: GM-CSF promotes PECAM1 expression, angiogenesis, and vascular maturation in ECs by upregulating VEGF and Ang-1 in PCs. These effects enhance the interaction between endothelial cells and pericytes, thereby contributing to vascular stabilization and improved wound healing.
Exosome-mediated neuroprotection in vascular dementia: Mechanisms, molecular pathways, and therapeutic prospects.
Fazli F, Davoody S, Vissers N … +4 more , Bordbar S, Rahbarghazi R, Karimipour M, Taiefi Nasrabadi H
Mol Cell Probes · 2026 Jun · PMID 41722741 · Publisher ↗
Exosomes, a specialized class of extracellular vesicles, exhibit significant therapeutic potentials for neurological disorders, in particular for vascular dementia (VaD). VaD is the second most common form of dementia, c...
Exosomes, a specialized class of extracellular vesicles, exhibit significant therapeutic potentials for neurological disorders, in particular for vascular dementia (VaD). VaD is the second most common form of dementia, characterized by cognitive and behavioral impairments. VaD is often linked to hippocampal damage resulting from its vulnerable vascular structure, which disrupts memory formation and retrieval. Secreted by various cell types within the central nervous system, exosomes mediate intercellular communication by transporting bioactive molecules. Growing evidence indicates that exosomes enhance synaptic plasticity, modulate neuroinflammation, inhibit apoptosis, and promote angiogenesis, supporting their therapeutic potentials in VaD. Given the urgent need for effective treatments and the unique ability of exosomes to cross the blood-brain barrier (BBB) and deliver multi-targeted therapies, research in this field is critically important. It offers a viable pathway toward the development of disease-modifying interventions for a condition that is currently managed primarily through symptomatic treatment. This review summarizes current knowledge on the functions of exosomes in the central nervous system, explores recent advances in exosome-based strategies for VaD, and discusses ongoing challenges and future directions for their clinical translation.
SIK1 alleviates myocardial hypoxia-reperfusion injury via promoting MEF2-mediated SIRT1 transcription.
Gong L, Chen L, Han S … +1 more , Sheng L
Mol Cell Probes · 2026 Jun · PMID 41690562 · Publisher ↗
Myocardial Hypoxia-Reperfusion (H/R) injury is a major challenge in coronary artery disease treatment. This article explores the potential mechanism of salt inducible kinase 1 (SIK1) in H/R injury. This study used H9C2 c...
Myocardial Hypoxia-Reperfusion (H/R) injury is a major challenge in coronary artery disease treatment. This article explores the potential mechanism of salt inducible kinase 1 (SIK1) in H/R injury. This study used H9C2 cardiomyocytes as the model. By constructing SIK1 overexpression and myocyte enhancer factor 2 (MEF2) silencing vectors, and combining qRT-PCR, CCK8, 5-Ethynyl-2'-deoxyuridine, flow cytometry, Western blot, JASPAR prediction, luciferase assay and chromatin immunoprecipitation experiments, it explored the effects and mechanisms of SIK1 on H/R cardiomyocytes from multiple dimensions. H/R impaired H9C2 cells (reduced viability, increased apoptosis/ROS/Caspase-9/12/Cytochrome C, downregulated MEF2/Sirtuin 1 (SIRT1)), which SIK1 overexpression reversed. MEF2 silencing blocked SIK1's protection; JASPAR, luciferase assay and Chromatin Immunoprecipitation confirmed MEF2 directly bound to SIRT1 promoter and activated its transcription. SIK1 alleviates H/R-induced myocardial cell damage in association with the upregulation of MEF2 and subsequent MEF2-mediated transcriptional activation of SIRT1.
The function and mechanism of LINC01583 on Osimertinib resistance in non-small cell lung cancer.
Wang X, Xu T, Xu S … +1 more , Liu N
Mol Cell Probes · 2026 Jun · PMID 41690561 · Publisher ↗
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with a steady increase in incidence. PURPOSE: This study aimed to confirm the role of LINC01583 on NSCLC progression and Osimertini...
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with a steady increase in incidence. PURPOSE: This study aimed to confirm the role of LINC01583 on NSCLC progression and Osimertinib (Osi) resistance. METHODS: The interactions of LINC01583, miR-4640-5p, and CHD8 were confirmed by RNA pulldown and Luciferase assay. The ROC curve was utilized to assess the discriminatory ability of LINC01583 for patients with Osi-resistant. NSCLC cell lines H1975 and PC9 were selected, and Osi-resistant cell lines were established by drug administration using the concentration gradient escalation method. The effect of LINC01583 on lung cancer drug-resistant cell lines was evaluated using CCK8, Transwell assay, and rescue experiments. RESULTS: In NSCLC cell lines and patients, the expression of LINC01583 and CHD8 was significantly increased, while miR-4640-5p expression was significantly decreased. Mechanistically, knockout of LINC01583 suppressed the migration ability of Osi-resistant cells and increased their sensitivity to Osi. Upregulation of LINC01583 can significantly promote the migration ability of lung cancer cell parent lines and reduce their sensitivity to Osi. Rescue experiments showed that co-transfection of miR-4640-5p inhibitor partially reversed the inhibitory effects of LINC01583 knockdown. LINC01583 acted as a molecular sponge for miR-4640-5p and regulated CHD8 expression by competitive binding. CONCLUSION: In this study, we revealed LINC01583 as a key oncogenic driver that promotes both NSCLC progression and Osi resistance by functioning as a competing endogenous RNA (ceRNA) for miR-4640-5p, thereby upregulating its target gene CHD8.
Metformin and oncogenic pathways: Crosstalk between energy sensing and tumor progression.
Zhang Y, Zhao L, Zhang K … +1 more , Gao Y
Mol Cell Probes · 2026 Apr · PMID 41687746 · Publisher ↗
Metformin, a widely prescribed oral biguanide for type 2 diabetes mellitus, has gained significant attention as a potential anti-cancer agent. Beyond its established role in improving insulin sensitivity and lowering blo...
Metformin, a widely prescribed oral biguanide for type 2 diabetes mellitus, has gained significant attention as a potential anti-cancer agent. Beyond its established role in improving insulin sensitivity and lowering blood glucose, preclinical and epidemiological studies suggest that metformin exerts anti-tumor effects through both insulin-dependent and insulin-independent mechanisms. Central to its activity is the activation of AMP-activated protein kinase (AMPK), which disrupts the mammalian target of rapamycin (mTOR) pathway, leading to cell cycle arrest, apoptosis, and reduced tumor growth. Additionally, metformin modulates oncogenic signaling networks such as PI3K/Akt, Erk, and receptor tyrosine kinases, while influencing tumor metabolism, angiogenesis, and immune responses. By inhibiting mitochondrial complex I, metformin interferes with cancer cell bioenergetics and the Warburg effect, further contributing to its anti-cancer potential. Clinical studies, however, have yielded mixed results, underscoring the complexity of metformin's effects and the need for rigorous investigation. This review highlights the multifaceted mechanisms by which metformin impacts tumor progression and discusses its promise and challenges as a therapeutic agent in cancer prevention and treatment.
Stem cell-derived and plant-derived exosomes: Promising therapeutics for skin healing and regeneration.
Wang X, Wang W, Yao R … +2 more , Liu Z, Wang Q
Mol Cell Probes · 2026 Apr · PMID 41655911 · Publisher ↗
Stem cell-derived and plant-derived exosomes are emerging as promising therapeutic agents in cutaneous repair, regeneration, and rejuvenation. They facilitate wound healing and skin revitalization through multifaceted me...
Stem cell-derived and plant-derived exosomes are emerging as promising therapeutic agents in cutaneous repair, regeneration, and rejuvenation. They facilitate wound healing and skin revitalization through multifaceted mechanisms, including immunomodulation, promotion of cellular differentiation, and stimulation of angiogenesis. Additionally, their ability to modulate collagen production and remodeling underscores their potential in addressing skin aging and improving cosmetic outcomes. Consequently, exosome-based therapies show promise for a range of conditions, from challenging wounds and skin aging to pigmentary disorders, hair loss, certain immune-mediated dermatoses. To ensure a comprehensive and unbiased synthesis of the current evidence, this systematic review was conducted following a structured methodology, encompassing a search across multiple major databases over a defined 20-year period. This review systematically outlines the roles and applications of commonly employed plant exosomes and stem cell exosomes in recent years' advancements in skin repair and cosmetic dermatology. By synthesizing the current understanding of their mechanisms and clinical potential, this review aims to highlight viable therapeutic strategies that bridge the gap between medical dermatology and aesthetic medicine.
Emerging roles of artificial intelligence/machine learning (AI/ML) towards new understandings in molecular crosstalk between circRNA-CUL3-TKI to resensitize chemoresistant cancers.
Dutta P, Middya S, Shome S … +3 more , Gupta MK, Dharmalingam P, Sudandiradoss C
Mol Cell Probes · 2026 Apr · PMID 41621693 · Publisher ↗
Cancer arises and is resistant to therapy via intricate molecular networks that are poorly characterised. While individually, Cullin-3 (CUL3) and circular RNAs (circRNAs) have been reported to modulate cancer, their syne...
Cancer arises and is resistant to therapy via intricate molecular networks that are poorly characterised. While individually, Cullin-3 (CUL3) and circular RNAs (circRNAs) have been reported to modulate cancer, their synergistic effect in the modulation of tyrosine kinase inhibitor (TKI) resistance is yet to be studied. An emerging circRNA-CUL3-TKI regulatory framework is highlighted as a potential contributor to oncogenesis and drug sensitivity in this review. We discuss how circRNA-associated networks may influence CUL3-dependent pathways implicated in tumour resistance to therapy by modulating autophagy, ferroptosis, stress-responses, and redox signalling. Exosomal circRNAs and circRNAs of the CUL3 gene itself are highlighted as dynamic mediators of resistance as well as biomarkers. How they interact with Kelch-like ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (KEAP1-NRF2) signalling reveals that they enhance tumour survival under therapy pressure. By highlighting key processes of carcinogenesis and resistance, the circRNA-CUL3-TKI axis represents a testable therapeutic framework. Modeling circRNA networks, predicting TKI response, finding biomarkers, and developing personalised treatment plans are all made possible by applications of artificial intelligence and machine learning (AI/ML), as explored in this review. Antisense oligonucleotides, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based molecules, neddylation inhibitors or PROteolysis TArgeting Chimera (PROTACs) are examples of potential interventions that, when combined with AI/ML techniques, improve therapeutic efficacy and may inform future desensitisation strategies. These collectively emphasize the emerging applications for AI/ML in understanding the circRNA-CUL3-TKI crosstalk and developing methods to resensitize cancers that are resistant to therapy.
The role of WNT10B expression in the prognosis of colorectal cancer: A retrospective study based on TCGA database and clinical data.
Shao J, Zheng X, Yang L … +7 more , Yu Q, Jin Z, Yang R, Zhao Z, Liu B, Wang R, Wang M
Mol Cell Probes · 2026 Apr · PMID 41605336 · Publisher ↗
OBJECTIVE: To evaluate the prognostic value of WNT10B expression in colorectal cancer (CRC) for personalized management. METHODS: We analyzed a TCGA cohort of 644 CRC patients to assess differential expression of WNT fam...
OBJECTIVE: To evaluate the prognostic value of WNT10B expression in colorectal cancer (CRC) for personalized management. METHODS: We analyzed a TCGA cohort of 644 CRC patients to assess differential expression of WNT family genes between 51 paired tumor-normal samples. Patients were stratified by WNT10B expression to compare overall survival (OS) and progression-free interval (PFI). Prognostic factors were identified via univariate and multivariate Cox regression. For validation, WNT10B protein expression was examined by immunohistochemistry in a separate cohort of 176 CRC patients who underwent surgery at our institution (2016-2020). Kaplan-Meier analysis and univariate Cox regression were used to correlate WNT10B levels with OS and disease-free survival (DFS). RESULTS: According to TCGA data, WNT10B was upregulated in CRC tumors. Elevated expression was correlated with reduced OS and PFI. Univariate analysis for OS implicated high WNT10B, age >65, lymph node/distant metastasis, positive margin, deep invasion, and abnormal CEA. For PFI, significant factors included high WNT10B, lymph node/distant metastasis, positive margin, deep invasion, and abnormal CEA. Multivariate analysis confirmed high WNT10B, age >65, and a positive margin as independent prognostic factors for OS. High WNT10B expression, distant metastasis, invasion depth and abnormal carcinoembryonic antigen level are the risk factors for independently predicting high tumor recurrence; Postoperative Kaplan-Meier analysis revealed that reduced WNT10B expression was associated with prolonged overall survival (OS), while disease-free survival (DFS) also tended to be longer in the low-expression group, although this trend did not reach statistical significance. Univariate Cox regression identified several factors adversely affecting OS, including elevated WNT10B expression, age ≥65 years, lymph node metastasis, distant metastasis, positive surgical margin, vascular invasion, and perineural invasion. Lymph node metastasis, distant metastasis, vascular invasion, and perineural invasion were also associated with increased recurrence risk. Multivariate analysis confirmed that age ≥65 years, distant metastasis, and vascular invasion were independent predictors of shorter OS. Distant metastasis emerged as an independent risk factor for tumor recurrence. CONCLUSION: WNT10B is upregulated in colorectal cancer and correlates with unfavorable outcomes, suggesting its potential utility as a prognostic biomarker and therapeutic target.
Exosomal IGFALS as a prognostic biomarker in hepatocellular Carcinoma: Associations with immune infiltration and clinical outcomes.
Fan L, Wang Z, Tao T … +6 more , Huang D, Tang X, Wang R, Qin Z, Xie B, Tan Y
Mol Cell Probes · 2026 Apr · PMID 41581825 · Publisher ↗
PURPOSE: This investigation seeks to examine the relationship between exosomal Insulin-like Growth Factor Binding Protein Acid Labile Subunit (IGFALS) gene expression, immune infiltration, and clinical outcomes in indivi...
PURPOSE: This investigation seeks to examine the relationship between exosomal Insulin-like Growth Factor Binding Protein Acid Labile Subunit (IGFALS) gene expression, immune infiltration, and clinical outcomes in individuals with hepatocellular carcinoma (HCC). METHOD: Clinical data and IGFALS expression levels were obtained from the TCGA and GEO databases. Immunohistochemistry was performed to confirm IGFALS expression in both HCC and adjacent non-tumor tissues. To validate survival analyses, restricted cubic spline models were used to explore associations between overall survival (OS) and the expression of IGFALS in liver hepatocellular carcinoma (LIHC). Gene set enrichment analysis (GSEA) identified IGFALS-associated pathways, while Gene set enrichment analysis (ssGSEA) evaluated IGFALS-immune cell infiltration correlations. Functional characterization included proliferation, migration/invasion, molecular profiling, and apoptosis assays. RESULT: Compared to normal tissues, IGFALS expression levels were notably decreased in tumor tissues. A notable link was detected between IGFALS expression and multiple clinical factors, including gender, weight, residual tumor, adjacent hepatic tissue inflammation, vascular invasion, AFP, BCLC, tumor size, multinodular, TACE, and satellite lesion in HCC. Reduced IGFALS expression in HCC was correlated with decreased OS. Moreover, the IGFALS level in malignant tumor cells post-immunotherapy was observed to be markedly higher than that in the pre-treatment phase. A strong association between IGFALS and immune infiltration levels was also established. At the same time, in vitro experiments also verified the function of the IGFALS gene. CONCLUSION: The exosomal IGFALS gene holds potential as a prospective indicator for assessing the outcome of individuals with HCC.
The HPV-E7/miR-106a/RUNX3/TGF-β1 axis regulates malignant progression in both HPV-positive and negative head and neck squamous cell carcinoma.
Zhang Y, Li X, Liu Y … +4 more , Wu Y, Li C, Zhang C, Liu Z
Mol Cell Probes · 2026 Feb · PMID 41456831 · Publisher ↗
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) remains a prevalent malignancy worldwide, posing significant health threats due to its high recurrence and metastatic potential. HPV-positive and negative HNSCC s...
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) remains a prevalent malignancy worldwide, posing significant health threats due to its high recurrence and metastatic potential. HPV-positive and negative HNSCC subtypes exhibit distinct prognostic profiles and their underlying pathogenic mechanisms remain poorly characterized. METHODS: Four HNSCC cell lines were selected: two HPV-positive (UM-SCC-47 and UPCI-SCC-090) and two HPV-negative (FaDu and UM-SCC-4). Basal miR-106a expression was measured in HPV-positive and -negative cells, followed by RT-qPCR validation of miR-106a, HPV-E7, RUNX3 overexpression and knockdown efficiency. Functional assays included CCK-8 for proliferation, wound healing for migration, Transwell for invasion, and flow cytometry for apoptosis. RT-qPCR quantified HPV-E7, miR-106a, RUNX3, and TGF-β1 mRNA levels; RUNX3 and TGF-β1 protein expression was assessed via Western blot. Dual-luciferase reporter assays confirmed the direct targeting of miR-106a to RUNX3. Finally, xenograft nude mouse models assessed miR-106a's effects on tumor growth and downstream molecular regulation in HPV-positive and -negative HNSCC. RESULTS: Comparative analysis revealed that miR-106a was significantly upregulated in HPV-positive HNSCC cells compared to their HPV-negative counterparts. Functional assays demonstrated that miR-106a overexpression enhanced HNSCC cell proliferation, migration, and invasion while suppressing apoptosis, whereas ectopic expression of RUNX3 exerted opposing effects on these oncogenic phenotypes. Mechanistically, miR-106a overexpression transcriptionally downregulated RUNX3 and concurrently elevated TGF-β1 expression, while RUNX3 overexpression inversely suppressed TGF-β1 levels. Dual-luciferase reporter assays confirmed a direct binding interaction between miR-106a and the 3'UTR of RUNX3. Rescue experiments further established that HPV E7-driven oncogenic effects-enhanced proliferation, migration, invasion, and apoptosis suppression-were abrogated by miR-106a inhibition, concomitant with restored expression of RUNX3 and attenuated TGF-β1 signaling. In vivo studies corroborated these findings, showing that miR-106a overexpression accelerated tumor growth in xenograft models, accompanied by progressive RUNX3 downregulation and TGF-β1 upregulation, consistent with its in vitro regulatory axis. CONCLUSIONS: Our findings suggest that the E7/miR-106a/RUNX3/TGF-β1 axis modulates proliferation, migration, invasion, and apoptosis in HPV-positive versus negative HNSCC, implicating its pathogenic role in tumor progression.
Identification and experimental validation of biomarkers for acute myeloid leukemia based on single-cell RNA sequencing data.
Yang X, Zhou S, Chen Y … +4 more , Wang Y, Cheng Y, Zhang C, Li Q
Mol Cell Probes · 2026 Feb · PMID 41448409 · Publisher ↗
BACKGROUND: Acute myeloid leukemia (AML) is a highly diverse malignant tumor at the molecular level with a high mortality rate. However, its underlying mechanisms remain poorly understood, and reliable biomarkers are lac...
BACKGROUND: Acute myeloid leukemia (AML) is a highly diverse malignant tumor at the molecular level with a high mortality rate. However, its underlying mechanisms remain poorly understood, and reliable biomarkers are lacking. METHODS: AML-related biomarkers were identified through a comprehensive analysis of single-cell RNA sequencing (scRNA-seq), Mendelian randomization (MR), and gene regulatory networks. The biomarkers were then subjected to GSEA enrichment analysis and in vitro experimental validation. RESULTS: scRNA-seq identified a total of 22,742 cells with detectable gene expression. Among the differentially expressed genes in the cells, 174 marker genes were screened out. MR analysis of marker genes showed that ITGB2, AIF1, CA2, CST7, and JCHAIN had a significant causal relationship with AML. Cumulative recovery curve analysis showed that AIF1, CST7, and ITGB2 were in the top motifs with the highest normalized enrichment scores. Therefore, they were recorded as biomarkers. Cellular experiments confirmed that AIF1, CST7, and ITGB2 promote cell proliferation and inhibit apoptosis. CONCLUSION: This study identified AIF1, CST7, and ITGB2 as biomarkers for AML through scRNA-seq, MR, and transcription factor enrichment analysis. Additionally, in vitro experiments, including cell transfection, cell proliferation, and flow cytometry, validated the important role of these biomarkers in promoting the malignant phenotype of AML.
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