Cell Cycle [JOURNAL]
Sun
200 papers
Cell death in atherosclerosis.
Ni D, Lei C, Liu M … +3 more , Peng J, Yi G, Mo Z
Cell Cycle · 2024 Mar · PMID 38678316 · Full text
A complex and evolutionary process that involves the buildup of lipids in the arterial wall and the invasion of inflammatory cells results in atherosclerosis. Cell death is a fundamental biological process that is essent...
A complex and evolutionary process that involves the buildup of lipids in the arterial wall and the invasion of inflammatory cells results in atherosclerosis. Cell death is a fundamental biological process that is essential to the growth and dynamic equilibrium of all living things. Serious cell damage can cause a number of metabolic processes to stop, cell structure to be destroyed, or other irreversible changes that result in cell death. It is important to note that studies have shown that the two types of programmed cell death, apoptosis and autophagy, influence the onset and progression of atherosclerosis by controlling these cells. This could serve as a foundation for the creation of fresh atherosclerosis prevention and treatment strategies. Therefore, in this review, we summarized the molecular mechanisms of cell death, including apoptosis, pyroptosis, autophagy, necroptosis, ferroptosis and necrosis, and discussed their effects on endothelial cells, vascular smooth muscle cells and macrophages in the process of atherosclerosis, so as to provide reference for the next step to reveal the mechanism of atherosclerosis.
Osteopontin-driven partial epithelial-mesenchymal transition governs the development of middle ear cholesteatoma.
Zeng L, Xie L, Hu J … +4 more , He C, Liu A, Lu X, Zhou W
Cell Cycle · 2024 Mar · PMID 38662954 · Full text
Cholesteatoma is a common disease of the middle ear. Currently, surgical removal is the only treatment option and patients face a high risk of relapse. The molecular basis of cholesteatoma remains largely unknown. Here,...
Cholesteatoma is a common disease of the middle ear. Currently, surgical removal is the only treatment option and patients face a high risk of relapse. The molecular basis of cholesteatoma remains largely unknown. Here, we show that Osteopontin (OPN), a predominantly secreted protein, plays a crucial role in the development of middle ear cholesteatoma. Global transcriptome analysis revealed the loss of epithelial features and an enhanced immune response in human cholesteatoma tissues. Quantitative RT-PCR and immunohistochemical staining of middle ear cholesteatoma validated the reduced expression of epithelial markers, as well as the elevated expression of mesenchymal markers including Vimentin and Fibronectin, but not N-Cadherin, α-smooth muscle actin (α-SMA) or ferroptosis suppressor protein 1 (FSP1), indicating a partial epithelial-mesenchymal transition (EMT) state. Besides, the expression of OPN was significantly elevated in human cholesteatoma tissues. Treatment with OPN promoted cell proliferation, survival and migration and led to a partial EMT in immortalized human keratinocyte cells. Importantly, blockade of OPN signaling could remarkably improve the cholesteatoma-like symptoms in SD rats. Our mechanistic study demonstrated that the AKT-zinc finger E-box binding homeobox 2 (ZEB2) axis mediated the effects of OPN. Overall, these findings suggest that targeting the OPN signaling represents a promising strategy for the treatment of middle ear cholesteatoma.
Genetic predisposition of polymorphisms to lumbar disk herniation in the Chinese Han population.
Sun K, Liu R
Cell Cycle · 2024 Feb · PMID 38651735 · Full text
Bone morphogenetic protein 7 (BMP7) can induce skeletal formation, promote the differentiation of chondrocytes and osteoblasts, and ameliorate intervertebral disc degeneration. The study was designed to evaluate the rela...
Bone morphogenetic protein 7 (BMP7) can induce skeletal formation, promote the differentiation of chondrocytes and osteoblasts, and ameliorate intervertebral disc degeneration. The study was designed to evaluate the relationship of variants to LDH risk in the Chinese Han population. variants were genotyped with the Agena MassARRAY system among 690 LDH patients and 690 healthy controls. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression. Multi-factor dimension reduction (MDR) (version 3.0.2) software was used to evaluate the effect of variant-variant interaction on the susceptibility to LDH. Here, the risk-reducing association between rs230189 and LDH occurrence was found ( = 0.005, OR = 0.79). Specially, rs230189 was associated with decreased LDH risk in females ( = 0.001, OR = 0.60), elder group ( = 0.025, OR = 0.76), subjects with BMI < 24 kg/m ( = 0.027, OR = 0.48), nonsmokers ( = 0.001, OR = 0.66), and nondrinkers ( = 0.011, OR = 0.72). Moreover, rs1321862 might be the risk factor for LDH susceptibility among the participants with BMI < 24 kg/m ( = 0.024, OR = 1.84). MDR results displayed that rs230189 was the greatest attribution factor on LDH risk in the single-locus model, with an information gain of 0.44%. The present study demonstrated that rs230189 g.55771443A>C may play a protective role against LDH risk. Our findings may help to understand the potential mechanism of in LDH susceptibility.
Discovery of common molecular signatures and drug repurposing for COVID-19/Asthma comorbidity: ACE2 and multi-partite networks.
Xu J, Abdulsalam Khaleel R, Zaidan HK … +10 more , Faisal Mutee A, Fahmi Fawy K, Gehlot A, Abbas AH, Arias Gonzáles JL, Amin AH, Ruiz-Balvin MC, Imannezhad S, Bahrami A, Akhavan-Sigari R
Cell Cycle · 2024 Feb · PMID 38640424 · Full text
Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global coronavirus disease-2019 (COVID-...
Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global coronavirus disease-2019 (COVID-19) pandemic. This study aimed to elucidate potential therapeutic avenues by scrutinizing approved drugs through the identification of the genetic signature associated with SARS-CoV-2 infection in individuals with asthma. This exploration was conducted through an integrated analysis, encompassing interaction networks between the ACE2 receptor and common host (co-host) factors implicated in COVID-19/asthma comorbidity. The comprehensive analysis involved the identification of common differentially expressed genes (cDEGs) and hub-cDEGs, functional annotations, interaction networks, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and module construction. Interaction networks were used to identify overlapping disease modules and potential drug targets. Computational biology and molecular docking analyzes were utilized to discern functional drug modules. Subsequently, the impact of the identified drugs on the expression of hub-cDEGs was experimentally validated using a mouse model. A total of 153 cDEGs or co-host factors associated with ACE2 were identified in the COVID-19 and asthma comorbidity. Among these, seven significant cDEGs and proteins - namely, , and -were recognized as pivotal host factors linked to ACE2. Regulatory network analysis of hub-cDEGs revealed eight top-ranked transcription factors (TFs) proteins and nine microRNAs as key regulatory factors operating at the transcriptional and post-transcriptional levels, respectively. Molecular docking simulations led to the proposal of 10 top-ranked repurposable drug molecules (Rapamycin, Ivermectin, Everolimus, Quercetin, Estradiol, Entrectinib, Nilotinib, Conivaptan, Radotinib, and Venetoclax) as potential treatment options for COVID-19 in individuals with comorbid asthma. Validation analysis demonstrated that Rapamycin effectively inhibited expression in the HDM-stimulated mice group ( < 0.01). This study unveils the common pathogenesis and genetic signature underlying asthma and SARS-CoV-2 infection, delineated by the interaction networks of ACE2-related host factors. These findings provide valuable insights for the design and discovery of drugs aimed at more effective therapeutics within the context of lung disease comorbidities.
SIRT3 suppression resulting from the enhanced β-catenin signaling drives glycolysis and promotes hypoxia-induced cell growth in hepatocellular carcinoma cells.
Ma R, Gao QY, Chen ZT … +6 more , Liao GH, Li ST, Cai JW, Luo NS, Chen H, Zhang HF
Cell Cycle · 2024 Feb · PMID 38626328 · Full text
The precise mechanisms underlying the inhibitory effects of SIRT3, a mitochondrial sirtuin protein, on hepatocellular carcinoma (HCC) development, as well as its impact on mitochondrial respiration, remain poorly underst...
The precise mechanisms underlying the inhibitory effects of SIRT3, a mitochondrial sirtuin protein, on hepatocellular carcinoma (HCC) development, as well as its impact on mitochondrial respiration, remain poorly understood. We assessed sirtuins 3 (SIRT3) levels in HCC tissues and Huh7 cells cultured under hypoxic condition. We investigated the effects of SIRT3 on cell proliferation, glycolytic metabolism, mitochondrial respiration, mitophagy, and mitochondrial biogenesis in Huh7 cells. Besides, we explored the potential mechanisms regulating SIRT3 expression in hypoxically cultured Huh7 cells. Gradual reduction in SIRT3 expressions were observed in both adjacent tumor tissues and tumor tissues. Similarly, SIRT3 expressions were diminished in Huh7 cells cultured under hypoxic condition. Forced expression of SIRT3 attenuated the growth of hypoxically cultured Huh7 cells. SIRT3 overexpression led to a decrease in extracellular acidification rate while increasing oxygen consumption rate. SIRT3 downregulated the levels of hexokinase 2 and pyruvate kinase M2. Moreover, SIRT3 enhanced mitophagy signaling, as indicated by mtKeima, and upregulated key proteins involved in various mitophagic pathways while reducing intracellular reactive oxygen species levels. Furthermore, SIRT3 increased proxisome proliferator-activated receptor-gamma coactivator 1α levels and the amount of mitochondrial DNA in Huh7 cells. Notably, β-catenin expressions were elevated in Huh7 cells cultured under hypoxic condition. Antagonists and agonists of β-catenin respectively upregulated and downregulated SIRT3 expressions in hypoxically cultured Huh7 cells. The modulationsof glycolysis and mitochondrial respiration represent the primary mechanism through which SIRT3, suppressed by β-catenin, inhibits HCC cell proliferation.
Role of β3 subunit of the GABA type A receptor in triple negative breast cancer proliferation, migration, and cell cycle progression.
Bundy J, Shaw J, Hammel M … +4 more , Nguyen J, Robbins C, Mercier I, Suryanarayanan A
Cell Cycle · 2024 Feb · PMID 38623967 · Full text
Triple negative breast cancer (TNBC) is known for its heterogeneous nature and aggressive onset. The unresponsiveness to hormone therapies and immunotherapy and the toxicity of chemotherapeutics account for the limited t...
Triple negative breast cancer (TNBC) is known for its heterogeneous nature and aggressive onset. The unresponsiveness to hormone therapies and immunotherapy and the toxicity of chemotherapeutics account for the limited treatment options for TNBC. Ion channels have emerged as possible therapeutic candidates for cancer therapy, but little is known about how ligand gated ion channels, specifically, GABA type A ligand-gated ion channel receptors (GABAR), affect cancer pathogenesis. Our results show that the GABA β3 subunit is expressed at higher levels in TNBC cell lines than non-tumorigenic cells, therefore contributing to the idea that limiting the GABAR via knockdown of the GABA β3 subunit is a potential strategy for decreasing the proliferation and migration of TNBC cells. We employed pharmacological and genetic approaches to investigate the role of the GABA β3 subunit in TNBC proliferation, migration, and cell cycle progression. The results suggest that pharmacological antagonism or genetic knockdown of GABA β3 subunit decreases TNBC proliferation and migration. In addition, GABA β3 subunit knockdown causes cell cycle arrest in TNBC cell lines via decreased cyclin D1 and increased p21 expression. Our findings suggest that membrane bound GABA receptors containing the β3 subunit can be further developed as a potential novel target for the treatment of TNBC.
Repression of YEATS2 induces cellular senescence in hepatocellular carcinoma and inhibits tumor growth.
Wu Q, Zheng Q, Yuan L … +9 more , Gao D, Hu Y, Jiang X, Zhai Q, Liu M, Xu L, Xu H, Ye J, Zhang F
Cell Cycle · 2024 Feb · PMID 38619971 · Full text
Hepatocellular carcinoma (HCC) stands as the third leading cause of cancer-related fatalities globally. In this study, we observed a significant increase in the expression level of the gene in HCC patients, and it is ne...
Hepatocellular carcinoma (HCC) stands as the third leading cause of cancer-related fatalities globally. In this study, we observed a significant increase in the expression level of the gene in HCC patients, and it is negatively correlated with the patients' survival rate. While we have previously identified the association between YEATS2 and the survival of pancreatic cancer cells, the regulatory mechanisms and significance in HCC are still to be fully elucidated. Our study shows that knockdown (KD) of YEATS2 expression leads to DNA damage, which in turn results in an upregulation of γ-H2A.X expression and activation of the canonical senescence-related pathway p53/p21Cip1. Moreover, our transcriptomic analysis reveals that YEATS2 KD cells can enhance the expression of p21Cip1 via the c-Myc/miR-93-5p pathway, consequently fostering the senescence of HCC cells. The initiation of cellular senescence through dual-channel activation suggests that YEATS2 plays a pivotal regulatory role in the process of cell proliferation. Ultimately, our research utilizing a nude mouse tumor model revealed a notable decrease in both tumor volume and weight after the suppression of YEATS2 expression. This phenomenon is likely attributable to the attenuation of proliferative cell activity, coupled with a concurrent augmentation in the population of natural killer (NK) cells. In summary, our research results have supplemented the understanding of the regulatory mechanisms of HCC cell proliferation and indicated that targeting YEATS2 may potentially inhibit liver tumor growth.
DNMT1-mediated epigenetic suppression of FBXO32 expression promoting cyclin dependent kinase 9 (CDK9) survival and esophageal cancer cell growth.
Song XQ, Chen BB, Jin YM … +1 more , Wang CY
Cell Cycle · 2024 Feb · PMID 38597826 · Full text
Esophageal cancer (EC) is a common and serious form of cancer, and while DNA methyltransferase-1 (DNMT1) promotes DNA methylation and carcinogenesis, the role of F-box protein 32 (FBXO32) in EC and its regulation by DNMT...
Esophageal cancer (EC) is a common and serious form of cancer, and while DNA methyltransferase-1 (DNMT1) promotes DNA methylation and carcinogenesis, the role of F-box protein 32 (FBXO32) in EC and its regulation by DNMT1-mediated methylation is still unclear. FBXO32 expression was examined in EC cells with high DNMT1 expression using GSE163735 dataset. RT-qPCR assessed FBXO32 expression in normal and EC cells, and impact of higher FBXO32 expression on cell proliferation, migration, and invasion was evaluated, along with EMT-related proteins. The xenograft model established by injecting EC cells transfected with FBXO32 was used to evaluate tumor growth, apoptosis, and tumor cells proliferation and metastasis. Chromatin immunoprecipitation (ChIP) assay was employed to study the interaction between DNMT1 and FBXO32. HitPredict, co-immunoprecipitation (Co-IP), and Glutathione-S-transferase (GST) pulldown assay analyzed the interaction between FBXO32 and cyclin dependent kinase 9 (CDK9). Finally, the ubiquitination assay identified CDK9 ubiquitination, and its half-life was measured using cycloheximide and confirmed through western blotting. DNMT1 negatively correlated with FBXO32 expression in esophageal cells. High FBXO32 expression was associated with better overall survival in patients. Knockdown of DNMT1 in EC cells increased FBXO32 expression and suppressed malignant phenotypes. FBXO32 repressed EC tumor growth and metastasis in mice. Enrichment of DNMT1 in FBXO32 promoter region led to increased DNA methylation and reduced transcription. Mechanistically, FBXO32 degraded CDK9 through promoting its ubiquitination.
Homologous recombination contributes to the repair of acetaldehyde-induced DNA damage.
Yamazaki K, Iguchi T, Kanoh Y … +8 more , Takayasu K, Ngo TTT, Onuki A, Kawaji H, Oshima S, Kanda T, Masai H, Sasanuma H
Cell Cycle · 2024 Feb · PMID 38571319 · Full text
Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is prevalently present in our environment, e.g. in alcohol, tobacco, and food. Although aldehyde potentially promotes crosslinking reactions am...
Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is prevalently present in our environment, e.g. in alcohol, tobacco, and food. Although aldehyde potentially promotes crosslinking reactions among biological substances including DNA, RNA, and protein, it remains unclear what types of DNA damage are caused by acetaldehyde and how they are repaired. In this study, we explored mechanisms involved in the repair of acetaldehyde-induced DNA damage by examining the cellular sensitivity to acetaldehyde in the collection of human TK6 mutant deficient in each genome maintenance system. Among the mutants, mismatch repair mutants did not show hypersensitivity to acetaldehyde, while mutants deficient in base and nucleotide excision repair pathways or homologous recombination (HR) exhibited higher sensitivity to acetaldehyde than did cells. We found that acetaldehyde-induced RAD51 foci representing HR intermediates were prolonged in HR-deficient cells. These results indicate a pivotal role of HR in the repair of acetaldehyde-induced DNA damage. These results suggest that acetaldehyde causes complex DNA damages that require various types of repair pathways. Mutants deficient in the removal of protein adducts from DNA ends such as and cells exhibited hypersensitivity to acetaldehyde. Strikingly, the double mutant deficient in both TDP1 and RAD54 showed similar sensitivity to each single mutant. This epistatic relationship between and suggests that the protein-DNA adducts generated by acetaldehyde need to be removed for efficient repair by HR. Our study would help understand the molecular mechanism of the genotoxic and mutagenic effects of acetaldehyde.
REV7-p53 interaction inhibits ATM-mediated DNA damage signaling.
Biller M, Kabir S, Boado C … +8 more , Nipper S, Saffa A, Tal A, Allen S, Sasanuma H, Dréau D, Vaziri C, Tomida J
Cell Cycle · 2024 Feb · PMID 38557443 · Full text
REV7 is an abundant, multifunctional protein that is a known factor in cell cycle regulation and in several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, and DNA Double-...
REV7 is an abundant, multifunctional protein that is a known factor in cell cycle regulation and in several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, and DNA Double-Strand Break (DSB) repair pathway choice. Thus far, no direct role has been studied for REV7 in the DNA damage response (DDR) signaling pathway. Here we describe a novel function for REV7 in DSB-induced p53 signaling. We show that REV7 binds directly to p53 to block ATM-dependent p53 Ser15 phosphorylation. We also report that REV7 is involved in the destabilization of p53. These findings affirm REV7's participation in fundamental cell cycle and DNA repair pathways. Furthermore, they highlight REV7 as a critical factor for the integration of multiple processes that determine viability and genome stability.
Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab.
Wójcik M, Plata-Babula A, Głowaczewska A … +4 more , Sirek T, Orczyk A, Małecka M, Grabarek BO
Cell Cycle · 2024 Feb · PMID 38557266 · Full text
Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate alterations in the expression patterns of genes encoding MAP...
Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate alterations in the expression patterns of genes encoding MAPKs and microRNA (miRNA) molecules that potentially regulate their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes when exposed to bacterial lipopolysaccharide A (LPS) and adalimumab. HaCaT cells underwent treatment with 1 µg/mL LPS for 8 hours, followed by treatment with 8 µg/mL adalimumab for 2, 8, or 24 hours. Untreated cells served as controls. The molecular analysis involved microarray, quantitative real-time polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA) analyses. Changes in the expression profile of seven mRNAs: dual specificity phosphatase 1 (, dual specificity phosphatase 3 (, dual specificity phosphatase 4 (, mitogen-activated protein kinase 9 (, mitogen-activated protein kinase kinase kinase 2 (, mitogen-activated protein kinase kinase 2 ( MAP kinase-activated protein kinase 2 , also known as in cell culture exposed to LPS or LPS and the drug compared to the control. It was noted that miR-34a may potentially regulate the activity of , , and , while miR-1275 is implicated in regulating expression. Additionally, miR-382 and miR-3188 are potential regulators of levels, and miR-200-5p is involved in regulating and levels. Thus, the analysis showed that these mRNA molecules and the proteins and miRNAs they encode appear to be useful molecular markers for monitoring the efficacy of adalimumab therapy.
Knockdown of hCINAP sensitizes colorectal cancer cells to ionizing radiation.
Shen M, Zhang Y, Wu F … +5 more , Shen M, Zhang S, Guo Y, Gan J, Wang R
Cell Cycle · 2024 Feb · PMID 38551450 · Full text
Colorectal cancer (CRC) poses a significant challenge in terms of treatment due to the prevalence of radiotherapy resistance. However, the underlying mechanisms responsible for radio-resistance in CRC have not been thoro...
Colorectal cancer (CRC) poses a significant challenge in terms of treatment due to the prevalence of radiotherapy resistance. However, the underlying mechanisms responsible for radio-resistance in CRC have not been thoroughly explored. This study aimed to shed light on the role of human coilin interacting nuclear ATPase protein (hCINAP) in radiation-resistant HT-29 and SW480 CRC cells (HT-29-IR and SW480-IR) and investigate its potential implications. Firstly, radiation-resistant CRC cell lines were established by subjecting HT-29 and SW480 cells to sequential radiation exposure. Subsequent analysis revealed a notable increase in hCINAP expression in radiation-resistant CRC cells. To elucidate the functional role of hCINAP in radio-resistance, knockdown experiments were conducted. Remarkably, knockdown of hCINAP resulted in an elevation of reactive oxygen species (ROS) generation upon radiation treatment and subsequent activation of apoptosis mediated by mitochondria. These observations indicate that hCINAP depletion enhances the radiosensitivity of CRC cells. Conversely, when hCINAP was overexpressed, it was found to enhance the radio-resistance of CRC cells. This suggests that elevated hCINAP expression contributes to the development of radio-resistance. Further investigation revealed an interaction between hCINAP and ATPase family AAA domain containing 3A (ATAD3A). Importantly, ATAD3A was identified as an essential factor in hCINAP-mediated radio-resistance. These findings establish the involvement of hCINAP and its interaction with ATAD3A in the regulation of radio-resistance in CRC cells. Overall, the results of this study demonstrate that upregulating hCINAP expression may improve the survival of radiation-exposed CRC cells. Understanding the intricate molecular mechanisms underlying hCINAP function holds promise for potential strategies in targeted radiation therapy for CRC. These findings emphasize the importance of further research to gain a comprehensive understanding of hCINAP's precise molecular mechanisms and explore its potential as a therapeutic target in overcoming radio-resistance in CRC. By unraveling the complexities of hCINAP and its interactions, novel therapeutic approaches may be developed to enhance the efficacy of radiation therapy and improve outcomes for CRC patients.
Identification and validation of key miRNAs and a microRNA-mRNA regulatory network associated with liver cancer.
Tang J, Li S, Zhou Z … +4 more , Chang W, Wang Y, Mei J, Zhou S
Cell Cycle · 2024 Feb · PMID 38547309 · Full text
MiRNAs play crucial regulatory roles in the growth and development of tumor cells by serving as carriers of post-transcriptional regulatory information derived from genes. Investigating the potential function and clinica...
MiRNAs play crucial regulatory roles in the growth and development of tumor cells by serving as carriers of post-transcriptional regulatory information derived from genes. Investigating the potential function and clinical significance of miRNA-mediated mRNA regulatory networks in liver cancer can offer novel insights and therapeutic strategies for the treatment of this disease. We identified 300 differentially expressed miRNAs, and five miRNAs were identified to be correlated with overall survival and could be used as an independent prognostic. GO enrichment analysis mainly included carboxylic acid biosynthesis, organic acid biosynthesis, peroxisomal membrane, microsomal membrane, DNA binding, C-acyltransferase activity, etc. KEGG enrichment analysis showed that the pathways of target genes related to liver cancer were mainly focused on butyric acid metabolism and partial amino acid metabolism. Eight of the top 10 HUB genes were associated with prognosis, and the expression of four genes was positively correlated with prognosis, of which ABAT, BHMT, and SHMT1 were target genes of hsa-miR-5003-3p. MiR-5003-3p inhibits ABAT/BHMT/SHMT1 expression, thereby promoting liver cancer development. Overall, our study provides new ideas for the treatment of liver cancer, and these five miRNAs may be independent prognostic biomarkers and therapeutic targets for liver cancer patients. And miR-5003-3p may be a critical factor in the mechanism of liver cancer development.
Hyaluronidase inhibitor sHA2.75 alleviates ischemia-reperfusion-induced acute kidney injury.
Zhang Y, Zhao H, Zhang J
Cell Cycle · 2024 Feb · PMID 38526145 · Full text
Hyaluronidases (HAases) are enzymes that degrade hyaluronic acid (HA) in the animal kingdom. The HAases-HA system is crucial for HA homeostasis and plays a significant role in biological processes and extracellular matri...
Hyaluronidases (HAases) are enzymes that degrade hyaluronic acid (HA) in the animal kingdom. The HAases-HA system is crucial for HA homeostasis and plays a significant role in biological processes and extracellular matrix (ECM)-related pathophysiological conditions. This study aims to explore the role of inhibiting the HAases-HA system in acute kidney injury (AKI). We selected the potent inhibitor "sHA2.75" to inhibit HAase activity through mixed inhibitory mechanisms. The ischemia-reperfusion mouse model was established using male BALB/c mice (7-9 weeks old), and animals were subjected to subcapsular injection with 50 mg/kg sHA2.75 twice a week to evaluate the effects of sHA2.75 on AKI on day 1, 5 and 14 after ischemia-reperfusion or sham procedure. Blood and tissue samples were collected for immunohistochemistry, biochemical, and quantitative analyses. sHA2.75 significantly reduced blood urea nitrogen (BUN) and serum creatinine levels in AKI mouse models. Expression of kidney injury-related genes such as Kidney injury molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), endothelial nitric oxide synthase (eNOS), type I collagen (Col1), type III collagen (Col3), alpha-smooth muscle actin (α-SMA) showed significant downregulation in mouse kidney tissues after sHA2.75 treatment. Moreover, sHA2.75 treatment led to decreased plasma levels of Interleukin-6 (IL-6) proteins and reduced mRNA levels in renal tissues of AKI mice. Inhibitor sHA2.75 administration in the AKI mouse model downregulated kidney injury-related biomarkers and immune-specific genes, thereby alleviating AKI in vivo. These findings suggest the potential use of HAase inhibitors for treating ischemic reperfusion-induced kidney injury.
Correction.
Cell Cycle · 2024 Feb · PMID 38526078 · Full text
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Effects of polymorphisms on susceptibility to coronary heart disease.
Yan Y, Du X, Dou X … +5 more , Li J, Zhang W, Yang S, Meng W, Tian G
Cell Cycle · 2024 Feb · PMID 38512812 · Full text
OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age...
OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What's more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. RESULTS: Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. CONCLUSION: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.
FUT4 promotes the progression of Cholangiocarcinoma by modulating epithelial-mesenchymal transition.
Liu E, Qian X, He Y … +1 more , Chen K
Cell Cycle · 2024 Jan · PMID 38466946 · Full text
Cholangiocarcinoma (CCA) is a common gastrointestinal malignancy characterized by a poor prognosis. Considering its prevalence, exploring its underlying molecular biological mechanisms is of paramount clinical importance...
Cholangiocarcinoma (CCA) is a common gastrointestinal malignancy characterized by a poor prognosis. Considering its prevalence, exploring its underlying molecular biological mechanisms is of paramount clinical importance. In this study, bioinformatics techniques were utilized to analyze CCA sample data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The analysis revealed a notable upregulation in FUT4 expression in CCA samples. To further investigate the functional implications of FUT4, in vivo and in vitro experiments were conducted, which demonstrated that FUT4 overexpression significantly enhances the proliferative and migratory capabilities of tumor cells. Subsequent sequencing analysis unveiled a correlation between FUT4 and epithelial-mesenchymal transition (EMT). Indeed, the pioneering discovery of elevated FUT4 expression in CCA was highlighted in this study. Further investigations into the function of FUT4 in CCA provided initial insights into its role in driving cancer progression via EMT. These findings present promising avenues for the diagnosis and treatment of CCA.[Figure: see text].
Sustained activation of NF-κB through constitutively active IKKβ leads to senescence bypass in murine dermal fibroblasts.
Harada M, Su-Harada K, Kimura T … +2 more , Ono K, Ashida N
Cell Cycle · 2024 Feb · PMID 38461418 · Full text
Although the transcription factor nuclear factor κB (NF-κB) plays a central role in the regulation of senescence-associated secretory phenotype (SASP) acquisition, our understanding of the involvement of NF-κB in the ind...
Although the transcription factor nuclear factor κB (NF-κB) plays a central role in the regulation of senescence-associated secretory phenotype (SASP) acquisition, our understanding of the involvement of NF-κB in the induction of cellular senescence is limited. Here, we show that activation of the canonical NF-κB pathway suppresses senescence in murine dermal fibroblasts. IκB kinase β (IKKβ)-depleted dermal fibroblasts showed ineffective NF-κB activation and underwent senescence more rapidly than control cells when cultured under 20% oxygen conditions, as indicated by senescence-associated β-galactosidase (SA-β-gal) staining and mRNA levels. Conversely, the expression of onstitutively ctive IKKβ (IKKβ-CA) was sufficient to drive senescence bypass. Notably, the expression of a degradation-resistant form of inhibitor of κB (IκB), which inhibits NF-κB nuclear translocation, abolished senescence bypass, suggesting that the inhibitory effect of IKKβ-CA on senescence is largely mediated by NF-κB. We also found that IKKβ-CA expression suppressed the derepression of genes and counteracted the senescence-associated loss of , a catalytic subunit of the Polycomb repressive complex 2 (PRC2). Moreover, pharmacological inhibition of Ezh2 abolished IKKβ-CA-induced senescence bypass. We propose that NF-κB plays a suppressive role in the induction of stress-induced senescence through sustaining expression.
Extracellular vesicles from : roles in the malignant phenotypes of gastric cancer.
Meng X, Ma G, Zhang X … +3 more , Yin H, Miao Y, He F
Cell Cycle · 2024 Feb · PMID 38446489 · Full text
The increase of the level has been previously identified in various cancers including gastric cancer (GC), but how the exerts its carcinogenic role in GC remains unclear. Several studies revealed that contributes to c...
The increase of the level has been previously identified in various cancers including gastric cancer (GC), but how the exerts its carcinogenic role in GC remains unclear. Several studies revealed that contributes to cancer progression via its secretion of extracellular vehicles (EVs). Hence, it's designed to reveal the influence of -derived EVs (Fn-EVs) in GC progression. The tumor and adjacent tissues were collected from 30 GC patients, and the abundance of was found to be highly expressed in tumor samples. The ultracentrifugation was employed to isolate EVs from and (), which were labeled Fn-EVs and -EVs, respectively. After treating GC cells with Fn-EVs and -EVs, cell counting kit 8, colony formation, wound healing as well as transwell assay were performed, which revealed that Fn-EVs effectively enhanced oxaliplatin resistance, and facilitated cell proliferation, migration, invasion, and stemness in GC cells while -EVs exert no significant effect on GC cells. Besides, the stemness and DNA repair of GC cells were also enhanced by Fn-EVs, as revealed by the sphere-forming assay and the detection of stemness- and DNA repair-associated proteins by western blotting. analyses demonstrated that Fn-EVs administration not only promoted GC tumor growth and liver metastasis but also conferred GC tumor resistance to oxaliplatin resistance. This study first revealed the contributive role of in GC development via Fn-EVs, which provided a better perspective for manipulating in treating GC patients with malignant phenotypes.
Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A.
Wójcik M, Zmarzły N, Derkacz A … +3 more , Kulpok-Bagiński T, Blek N, Grabarek BO
Cell Cycle · 2024 Feb · PMID 38445655 · Full text
Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes encoding MAPKs and micro...
Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes encoding MAPKs and microRNA (miRNA) molecules potentially regulating their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes exposed to bacterial lipopolysaccharide A (LPS) and cyclosporine A (CsA). HaCaT cells were treated with 1 µg/mL LPS for 8 h, followed by treatment with 100 ng/mL cyclosporine A for 2, 8, or 24 h. Untreated cells served as controls. The molecular analysis consists of microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay analyses. The statistical analysis of the obtained results was performed using Transcriptome Analysis Console and STATISTICA 13.5 PL with the statistical significance threshold of < 0.05. Changes in the expression profile of six mRNAs: dual-specificity phosphatase 1 (, dual-specificity phosphatase 4 (, mitogen-activated protein kinase kinase 2 (, mitogen-activated protein kinase kinase 7 (, mitogen-activated protein kinase kinase kinase 2 ( and mitogen-activated protein kinase 9 ( in cell culture exposed to LPS or LPS and the drug compared to the control. We observed that under the LPS and cyclosporine treatment, the expression o/ miR-34a, miR-1275, miR-3188, and miR-382 changed significantly ( < 0.05). We demonstrated a potential relationship between and miR-34a; and miR-34a, miR-382, and miR-3188; and miR-1275, and mir-200-5p; and mir-200-5p, which may be the subject of further research in the context of psoriasis.
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