Journal of Bioenergetics and Biomembranes最新文献

{"title":"MATR3 regulates METTL3-Mediated m⁶A modification of MSI2 mRNA to activate the Wnt/β-Catenin pathway, exacerbating myocardial fibrosis and atrial fibrillation.","authors":"Zihan Wei, Jing Li, Pinji Dai, Cheng Qian, Xiaoli Li","doi":"10.1007/s10863-026-10090-5","DOIUrl":"10.1007/s10863-026-10090-5","url":null,"abstract":"<p><p>To investigate the role and molecular mechanisms of the RNA-binding protein MATR3 in myocardial fibrosis of atrial fibrillation (AF). Expression of MATR3 and MSI2 in AF patients was analyzed using GEO datasets (GSE79768, GSE14975, GSE31821). Human atrial fibroblasts (HAFs) induced by Angiotensin II (Ang-II) were used as an in vitro cellular model of myocardial fibrosis. Expression and interactions of MATR3, METTL3, and MSI2 were validated by qRT-PCR and Western blot. The binding between MATR3 and METTL3 was confirmed by co-immunoprecipitation (Co-IP). The m⁶A modification level of MSI2 mRNA was detected by methylated RNA immunoprecipitation (MeRIP-qPCR). Cell proliferation, migration, and fibrotic phenotypes were evaluated by CCK-8, EdU, scratch, and Transwell assays, as well as detection of fibrosis markers. An Ang-II-induced mouse model of atrial fibrosis was constructed, and the in vivo effects of MATR3 were verified by HE staining, Masson's trichrome staining, and molecular detection. Analysis of GEO datasets showed that both MATR3 and MSI2 were highly expressed in AF patients. Ang-II treatment significantly upregulated the expression of MATR3 in HAFs, while knockdown of MATR3 inhibited Ang-II-induced proliferation, migration, and pro-fibrotic phenotypic changes in HAFs (reducing the expression of α-SMA, collagen I/III). Mechanistically, MATR3 interacted endogenously with METTL3 and stabilized the METTL3 protein by inhibiting proteasomal degradation. METTL3 mediated the m⁶A modification of MSI2 mRNA, enhancing its stability and promoting its expression. MSI2 exerted a pro-fibrotic effect by activating the Wnt/β-Catenin pathway. In vivo experiments confirmed that silencing MATR3 downregulated the expression of METTL3 and MSI2, inhibited the activation of the Wnt pathway, and alleviated Ang-II-induced atrial fibrosis in mice. MATR3 promotes myocardial fibrosis and exacerbates AF by regulating METTL3-mediated m⁶A modification of MSI2 mRNA to activate the Wnt/β-Catenin pathway. Targeting MATR3 may represent a potential therapeutic strategy for AF.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTGS2 as a potential target for apigenin to promote spinal cord injury repair.","authors":"Jialin Zhang, Min Zhao","doi":"10.1007/s10863-026-10094-1","DOIUrl":"10.1007/s10863-026-10094-1","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is characterized by damage to the spinal cord caused by various reasons, and there is a lack of effective drug treatments. Apigenin, a well-known natural small molecule drug, may serve as a therapeutic agent for a variety of diseases. However, the potential mechanisms by which Apigenin exerts its effects in SCI remain unclear. By utilizing an integrative multiomics strategy that combines network pharmacology, Mendelian randomization, and single-cell transcriptomic profiling, we established a systems-level target identification framework. Mechanistic analysis revealed a phytochemical‒neuropathy interactome, causal inference modeling (SMR) revealed target‒phenotype linkages and single-cell spatial mapping revealed the localization of target neural cell subtypes. In vitro experiments using PC12 cells and primary neuronal cells further validated the protective effects of apigenin against H2O2-induced neuronal injury. The results demonstrated that PTGS2, a key target identified through integrated analyses, exhibited elevated expression in SCI neurons. Apigenin treatment effectively mitigated H2O2-induced cellular damage while decreasing PTGS2 expression. These findings confirm that PTGS2 is a potential therapeutic target in SCI and highlight the value of a multiomics approach in overcoming traditional methodological limitations related to specificity and resolution. This study provides critical insights for advancing the clinical translation of apigenin and natural drug development strategies.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell-originated exosomal ZEB1 alleviates hypoxia/reperfusion-induced apoptosis, oxidative stress, and endoplasmic reticulum stress in cardiomyocytes via regulating UBIAD1.","authors":"Fan Zhao, Taimin Liu, Xinqiang Yu","doi":"10.1007/s10863-026-10095-0","DOIUrl":"10.1007/s10863-026-10095-0","url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction (AMI) is a major cardiovascular disease. Exosomes from mesenchymal stem cells (MSCs) are known to ameliorate myocardial ischemia-reperfusion (I/R) injury, and aberrant expression of UbiA prenyltransferase domain-containing protein 1 (UBIAD1) is linked to cardiovascular pathologies. However, it remains unclear whether MSC-derived exosomes mediate myocardial I/R injury by regulating UBIAD1.</p><p><strong>Methods: </strong>MSCs were identified by flow cytometry and differentiation assays (Alizarin Red and Oil Red O). Exosomes were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), western blot, and immunofluorescence. Differentially expressed genes were analyzed using bioinformatics analysis. An in vitro H/R damage model was established. Protein expression was examined by western blot. For function, the cell viability, lactate dehydrogenase (LDH), malonaldehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels were detected using corresponding assay kits. Cell apoptosis was examined using flow cytometry. Cross-analysis of the transcription factors predicting UBIAD1 in hTFtarget with highly expressed genes in GSE202991 was analyzed using a Venn diagram. Besides, the interaction between ZEB1 and UBIAD1 was predicted and verified via JASPAR database, chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assays.</p><p><strong>Results: </strong>Up-regulated UBIAD1 mitigated H/R-induced injury in AC16 cells. Conversely, silencing UBIAD1 abrogated MSC-Exo-induced action of mitigation on H/R-induced AC16 cell injury. ZEB1 could bond to UBIAD1. Moreover, exosomes derived from sh-ZEB1-transfected MSCs reduced H/R-induced apoptosis and oxidative stress in cardiomyocytes. Importantly, exosomal ZEB1 alleviated H/R‑induced apoptosis, oxidative stress, and endoplasmic reticulum stress (ERS) through increasing UBIAD1.</p><p><strong>Conclusion: </strong>MSC-derived exosomal ZEB1 remits H/R-stimulated cardiomyocyte apoptosis, oxidative stress, and ERS via regulating UBIAD1.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the therapeutic mechanisms of cinnamaldehyde in allergic rhinitis: a network Pharmacology and experimental approach.","authors":"Zhen Yan, Guoxiao Gu, Ru Wei, Xu Zhang, Xianyun Liu","doi":"10.1007/s10863-026-10089-y","DOIUrl":"10.1007/s10863-026-10089-y","url":null,"abstract":"<p><p>Cinnamaldehyde (CA), a bioactive compound with demonstrated anti-inflammatory and anti-oxidant properties, has been shown to ameliorate allergic rhinitis (AR) pathology. However, its precise mechanisms of action, particularly regarding modulation of ferroptosis and oxidative stress pathways, require further elucidation. Bioinformatics approaches were employed to predict putative targets of CA in AR. Network pharmacology analyses, incorporating protein-protein interaction (PPI) networks, hub gene identification, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, elucidated molecular interactions between CA and AR-associated targets. The functions of CA in interleukin-13 (IL-13)-stimulated human nasal epithelial cells (HNECs) were determined by testing cell viability, lactate dehydrogenase (LDH) activity, inflammatory response, apoptosis, oxidative stress, and ferroptosis. Bioinformatic analysis identified 423 potential targets of CA and 6,712 potential AR-related targets, with 285 shared proteins forming an intricate PPI network. These overlapping targets were significantly associated with key pathways including apoptosis, ferroptosis, tumor necrosis factor (TNF) signaling, and Toll-like receptor pathway. CA mitigated IL-13-evoked inflammatory response, apoptosis, oxidative stress, and ferroptosis in HNECs. Mechanistically, CA decreased toll-like receptor 4 (TLR4) expression in IL-13-stimulated HNECs. Increased TLR4 expression reversed the effects of CA on cell inflammation, apoptosis, oxidative stress, and ferroptosis in IL-13-stimulated HNECs. Our study demonstrates for the first time that CA protects against IL-13-induced cellular damage in HNECs by suppressing oxidative stress, apoptosis, ferroptosis, and inflammatory responses through the downregulation of TLR4.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2 X 7 receptor deficiency ameliorates high-fat-induced cardiac remodeling by improving oxidative stress through PI3K/AKT/GSK3β-mediated regulation of Nrf2.","authors":"Xiangxiang Shi, Yonggan Dong, Junfu Fan, Shengqu He, Shengban You, Jianjun Feng, Xin Zhong, Gaozan Tong, Zhouqing Huang","doi":"10.1007/s10863-026-10082-5","DOIUrl":"10.1007/s10863-026-10082-5","url":null,"abstract":"<p><p>Abnormal or excessive fat accumulation may lead to the development of cardiac remodeling. Yet, the mechanism of action remains unclear. We recently found that suppressing the P2 × 7 receptor (P2 × 7R) may alleviate high-fat (HF)-induced myocardial remodeling in mice. In this study, we further examined whether P2 × 7R affects oxidative stress, mainly nuclear factor E2-related factor 2 (Nrf2), in HF-induced cardiac remodeling. For in vivo testing, C57BL/6J wild-type mice and P2 × 7R−/− mice were given an HF diet or a standard diet (SD) for 24 weeks. For in vitro experiments, H9c2 cells were transfected with small-interfering RNA targeting P2 × 7R (si-P2 × 7R) or si-NC (Control), then treated with palmitic acid and a PI3K inhibitor. Echocardiograms were used to assess cardiac function post-modeling in mice. Immunohistochemistry, RT-PCR, and Western blot assessed mRNA and protein expression in cells and hearts. The TUNEL assay was used to evaluate cell death. P2 × 7R increased in heart tissues and H9c2 cells after stimulation by HF diet and PA, respectively. Moreover, P2 × 7R deficiency alleviated HF-induced pathological cardiac remodeling by improving the E’/A’ and E/A ratios, left ventricular ejection fraction (EF), and fractional shortening, and by decreasing inflammation, apoptosis, and oxidative stress induced by the HF diet. Mechanistically, we found that P2 × 7R can modulate Nrf2 activity via the PI3K/AKT/GSK3β signaling pathway. P2 × 7 receptor deficiency ameliorates cardiac remodeling induced by abnormal or excessive fat accumulation, reducing oxidative stress via PI3K/AKT/GSK3β-mediated regulation of Nrf2. P2 × 7R may serve as a new drug target for treating cardiac remodeling in obesity.Clinical trial number: Not applicable.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALK5 inhibition reduces HDM-induced inflammation and oxidative injury by regulating KLF4-mediated glycolysis in BEAS-2B cells.","authors":"Haixia Wang, Kun Luo, Shasha Li, Dan Jin, Ling Ou, Cuicui Liu, Qing Wu","doi":"10.1007/s10863-026-10098-x","DOIUrl":"10.1007/s10863-026-10098-x","url":null,"abstract":"<p><p>As an important transcription factor, activin receptor-like kinase 5 (ALK5) plays a crucial role in the development of various diseases. However, there have been no reports on whether ALK5 is involved in the pathogenesis of asthma, and further exploration is needed. An in vitro asthma model was constructed using house dust mite (HDM). Quantitative real-time polymerase chain reaction and western blot were used to detect the expression of ALK5. Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory factors. Oxidative stress-related factors and glycolysis-related indicators were analysed using commercial kits. Co-immunoprecipitation was used to assess the binding activity of ALK5 and Krüppel-like factor 4 (KLF4). Finaly, an HDM-induced asthmatic mouse model was established. H&E and PAS staining were used to evaluate the pathological status of mouse lungs, immunohistochemistry (IHC) was used to detect the expression of ALK5 and KLF4 in mouse lung tissue, and Masson staining was used to detect collagen deposition. The results showed that ALK5 was up-regulated in HDM-induced BEAS-2B cells. Silencing ALK5 suppressed inflammation and apoptosis in BEAS-2B cells. Furthermore, knockdown of ALK5 inhibited oxidative stress and promoted glycolysis in BEAS-2B cells. ALK5 specifically bound to KLF4 and promoted its protein degradation. Mechanistically, KLF4-mediated glycolysis was involved in the regulation of ALK5 in BEAS-2B cells. In vivo, ALK5 knockdown attenuated airway inflammation, reduced inflammatory cell infiltration, decreased collagen deposition, and improved lung histopathological damage. In conclusion, inhibiting ALK5 suppresses inflammation, apoptosis, and oxidative stress by regulating KLF4-mediated glycolysis in BEAS-2B cells, thus inhibiting the further development of asthma. Therefore, ALK5 may be a potential target for the clinical treatment of asthma.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shionone attenuates endoplasmic reticulum stress-associated ferroptosis in cardiomyocytes by reducing LCN2 and regulating PI3K/Akt signaling.","authors":"Chunni Gao, Xingjuan Gao, Jinshuang Li","doi":"10.1007/s10863-026-10092-3","DOIUrl":"10.1007/s10863-026-10092-3","url":null,"abstract":"<p><p>Ischemia/reperfusion-induced myocardial dysfunction remains a clinical problem and is associated to poor outcomes in patients with cardiovascular disorders, such as myocardial infarction. Shionone is a triterpenoid extracted from the herbal medicine Radix Asteris which has health benefits. This study aimed to explore the roles and functional mechanism of Shionone in regulating myocardial ischemia/reperfusion injury. The network pharmacology was performed to analyze the potential pathway interacted with Shionone in myocardial ischemia/reperfusion injury. The oxygen-glucose deprivation and reperfusion (OGD/R)-treated H9c2 cardiomyocytes and ischemia/reperfusion-induced murine models were regarded as in vitro and in vivo models. Lactate dehydrogenase (LDH), reactive oxygen species (ROS), glutathione (GSH) and iron levels were analyzed using specific kits. Related protein levels were detected by immunofluorescence staining and western blotting assays. Heart infarct in mice was investigated via TTC staining. Network pharmacology predicted LCN2 and PI3K/Akt signaling might be required by Shionone to involve in myocardial ischemia/reperfusion injury. Shionone mitigated OGD/R-induced ferroptosis through decreasing LDH release, ROS generation, iron and ACSL4 levels, and enhancing GSH, SLC7A11 an GPX4 levels in cardiomyocytes. Shionone attenuated OGD/R-induced endoplasmic reticulum stress through reducing CHOP, GRP-78, and phosphorylation levels of PERK and eIF2α. Endoplasmic reticulum stress inducer reversed the effects of Shionone on cardiomyocyte ferroptosis. Shionone decreased LCN2 expression and enhanced activation of PI3K/Akt signaling. Overexpressed LCN2 reversed the effects of Shionone on cardiomyocyte ferroptosis and endoplasmic reticulum stress in OGD/R-treated cardiomyocytes, and this function was mitigated via PI3K/Akt signaling activation. Shionone mitigated ischemia/reperfusion damage in murine heart by reducing heart infarct. Shionone attenuated endoplasmic reticulum stress-associated ferroptosis in cardiomyocytes through decreasing LCN2 and activating PI3K/Akt signaling, offering a basis for understanding the potentially cardioprotective potential of Shionone post ischemia/reperfusion injury.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EMF-induced mesenchymal stem cell migration is mediated by SOCE-dependent calcium influx and modulated by ROCK signaling.","authors":"Pin Zhao, Jiayuan Ou, Liming Bai, Mingsheng Zhang, Xinping Li","doi":"10.1007/s10863-026-10085-2","DOIUrl":"10.1007/s10863-026-10085-2","url":null,"abstract":"<p><p>Electromagnetic field (EMF) exposure promotes mesenchymal stem cell (MSCs) migration, a critical process in regenerative medicine. While calcium (Ca²⁺) signaling is implicated, the primary Ca²⁺ entry pathway and its downstream mechanisms remain elusive. This study investigates the hypothesis that store-operated calcium entry (SOCE) serves as a major Ca²⁺ influx mechanism and modulates the ROCK pathway to drive EMF-induced MSCs migration. Rat bone marrow-derived MSCs were exposed to a 50 Hz, 5 mT sinusoidal EMF. Cell migration was assessed via Transwell assays. Intracellular Ca²⁺ and SOCE activity were measured using Fluo-4 AM. Transcriptomic profiling was performed by RNA sequencing. Cytoskeletal reorganization (F-actin, acetylated α-tubulin) and protein expression (Orai1, ROCK1/2) were analyzed by immunofluorescence and western blotting, using pharmacological inhibitors (BTP2 for SOCE, Y-27632 for ROCK) and calcium chelators to dissect the pathway. EMF exposure significantly enhanced MSCs migration and activated calcium signaling pathways. This pro-migratory effect was strictly dependent on extracellular Ca²⁺ influx and was abolished by SOCE inhibition with BTP2. EMF upregulated the SOCE channel Orai1 and enhanced SOCE activity. Crucially, EMF suppressed ROCK1/2 expression under normal conditions, but this suppression was not reversed under SOCE inhibition or in low-calcium medium and EMF exposure increased ROCK1/2 expression in Ca²⁺-free medium (with 2 mM EGTA). SOCE inhibition also attenuated EMF-induced cytoskeletal reorganization, including perinuclear accumulation of acetylated α-tubulin and F-actin polymerization. Our findings establish SOCE-mediated Ca²⁺ influx as the critical driver of EMF-promoted MSCs migration. This process involves the upregulation of Orai1 and elicits a biphasic, context-dependent modulation of the ROCK pathway. The pro-migratory phenotype requires the synergy of SOCE-dependent Ca²⁺ influx and ROCK downregulation, leading to coordinated cytoskeletal remodeling. This study redefines the mechanistic understanding of EMF bioeffects, highlighting SOCE as a key regulator that integrates calcium signaling with cytoskeletal dynamics to control cell migration.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of UPK1A reduces the Escherichia coli-induced HIF-1α glycolytic pathway in colorectal adenocarcinoma.","authors":"Yue Wu, Yijun Zhang, Jian Lv, Yinzhong Wang","doi":"10.1007/s10863-025-10069-8","DOIUrl":"10.1007/s10863-025-10069-8","url":null,"abstract":"<p><p>Colorectal adenocarcinoma (COAD) poses a serious threat to the life of the patient. Notably, Uroplakin 1 A (UPK1A) is a prognostic biomarker for a variety of tumors. However, the role played by UPK1A in the occurrence and development of COAD and its associated molecular mechanisms still lacks a clear and in-depth understanding. The relationship between UPK1A expression and clinicopathological features, as well as patient prognosis, was examined through the use of online databases. Differences in UPK1A expression in COAD tissues and adjacent normal tissues were assessed in clinical samples. The effects of knocking down UPK1A under Escherichia coli (E. coli) co-culture/non-co-culture conditions on COAD cell proliferation, cell invasion, and apoptosis were investigated. In vivo subcutaneous tumor xenograft model, we knocked down the UPK1A gene in a tumor mouse model and assessed tumor growth. The effects of UPK1A and E. coli on glycolysis were investigated by detecting mRNA expression of glucose consumption, lactate production, HIF-1α, and glycolytic enzymes (GLUT1, LDHA, and PDK1). UPK1A was highly expressed in COAD tissues and showed a positive association with unfavorable outcomes in colorectal cancer patients. By knocking down UPK1A, co-culture conditions with E. coli inhibited COAD cell proliferation and invasion, promoted apoptosis, and reduced tumor growth. Knockdown of UPK1A inhibited COAD cell glycolysis by modulating HIF-1α signaling under E. coli co-culture conditions. It is suggested that UPK1A and E. coli synergistically promoted COAD cell proliferation, invasion, and tumor growth and inhibited apoptosis. By regulating HIF-1α signaling, UPK1A and E. coli were able to promote glycolysis in COAD cells. UPK1A and E. coli synergistically interfered with junctional COAD processes.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":"469-479"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of RNA-binding proteins in MAFLD: mechanistic insights and diagnostic biomarker potential via alternative splicing.","authors":"Panpan Xia, Xiaopeng Li, Jie Peng, Kaibo Hu, Jitao Ling, Yuting Wu, Jianqi Liang, Yunkun Liu, Yan Xiong, Jianping Liu, Deju Zhang, Xianrun Ma, Yixuan Chen, Jing Zhang, Peng Yu","doi":"10.1007/s10863-025-10078-7","DOIUrl":"10.1007/s10863-025-10078-7","url":null,"abstract":"<p><p>Metabolic associated fatty liver disease (MAFLD) is a highly prevalent global chronic liver disease. While abnormal expression of RNA-binding proteins (RBPs) has been implicated in MAFLD, their functional roles-particularly in regulating alternative splicing (AS)-remain poorly characterized. This study aimed to investigate the abnormal expression and regulatory mechanism of RBPs in MAFLD. The source data were obtained from the GSE130970 dataset of the Gene Expression Omnibus (GEO) database. Then, we utilized differential expression analysis to acquire the differentially expressed genes (DEGs) between different stages of MAFLD patients and normal patients. Alternative splicing analysis was performed via the ABLas pipeline to explore the alternative splicing events that may enhance and regulate the development of MAFLD. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were utilized via KOBAS2.0. Finally, quantitative real-time Polymerase Chain Reaction (RT-qPCR) and Western blotting analysis were performed to confirm the expression of significant RBPs. We observed a significant increase in the number of DEGs as the stages of MAFLD progressed. Furthermore, co-expression analysis suggested that abnormally expressed RBPs such as S100A4, CYCS, and JUN might participate in MAFLD development by potentially influencing the AS of downstream metabolism-related genes such as FAT1, SLCO2B1, and C4BPB. Moreover, we confirmed that the expression of the three RBPs (S100A4, CYCS and JUN) is significantly up-regulated in the liver through validation experiments. The abnormal up-regulated expression of RBPs (S100A4, CYCS and JUN) might contribute to the progression of MAFLD and hence they can be further regarded as potential therapeutic targets for MAFLD.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":"391-407"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}