Journal of Bioenergetics and Biomembranes最新文献

{"title":"DNA hypermethylation drives BVES-mediated autophagy to promote cisplatin resistance in lung adenocarcinoma.","authors":"Xiaoli Tan, Xiaodong Lv, Ruru Chen, Yufen Xu, Wenyu Chen","doi":"10.1007/s10863-026-10091-4","DOIUrl":"10.1007/s10863-026-10091-4","url":null,"abstract":"<p><p>Aberrant DNA methylation induces abnormal expression of drug-resistance genes, promoting drug resistance. This study identified specific DNA methylation patterns driving LUAD chemoresistance and explored their mechanisms. Blood vessel epicardial substance (BVES) expression and methylation were analyzed by using TCGA and MethylMix. Primers for the BVES CpG island were designed with MethPrimer. Pathways for BVES were analyzed by gene set enrichment analysis. Methylation-specific quantitative PCR detected the levels of BVES methylation. Quantitative reverse transcription polymerase chain reaction evaluated BVES expression, and western blot analyzed the expression of BVES, LC3, and P62. The cell counting kit-8 was used to determine IC50 and cell viability. Cell proliferation assessment was achieved by colony formation assay, and apoptosis was evaluated by flow cytometry. LC3 expression was observed through immunofluorescence. The findings displayed hypermethylation of BVES in LUAD tissues and cells, which was further elevated in the setting of cisplatin (DDP) resistance. The overexpression of BVES in A549/DDP cells substantially repressed their proliferation in response to DDP and markedly amplified the apoptotic effects induced by DDP. In the rescue experiments, autophagy stimulants effectively eliminated the DDP sensitivity enhancement caused by BVES overexpression in A549/DDP cells. In vivo assays confirmed that BVES overexpression suppressed autophagy and augmented the therapeutic impact of DDP. BVES hypermethylation, through the promotion of autophagy, reinforces resistance to DDP in LUAD. This study indicates that repressing BVES methylation and upregulating its expression may be a strategic way to combat cisplatin resistance in LUAD patients.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690132","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":"Vitamin B3 rescues mitochondrial homeostasis in dexamethasone-induced skeletal muscle atrophy by reducing oxidative stress.","authors":"Akash Mitra, Samanwita Mandal, Anna Timothy Dsouza, Debajit Chaudhury, Bipasha Bose, Sudheer Shenoy P","doi":"10.1007/s10863-026-10106-0","DOIUrl":"10.1007/s10863-026-10106-0","url":null,"abstract":"<p><p>Prolonged glucocorticoid exposure leads to oxidative stress, mitochondrial damage and impaired myogenesis reducing the overall health of the skeletal muscles. Dexamethasone (dex), a synthetic glucocorticoid, induces proteolysis and inflammation by disrupting cellular energetics and mitochondrial function. Vitamin B3 (vit B3), an NAD⁺ precursor, is known to be a natural antioxidant and anti-inflammatory compound. This study investigates the protective role of vit B3 against dex-induced skeletal muscle damage, focusing on mitochondrial homeostasis and the IKK/FoxO3a signalling axis. C2C12 myoblasts were treated with dex (200 µM) and/or vit B3 (1 mM). Oxidative stress, mitochondrial potential and DNA damage was evaluated using DCFDA, JC1, and γH2AX immunostaining, respectively. Gene expression analysis was performed to assess the mitochondrial fission/fusion and the extent of electron transport chain (ETC) gene expression. Protein expression of inflammatory (IKKα/β, NFκB) and atrophy markers were analysed using immunoblotting and flow cytometry. The extent of myogenic differentiation was evaluated using MyoD and MyHC1 immunostaining along with measurement of the morphometric parameters. Vit B3 treatment significantly enhanced C2C12 viability and reduced dex-induced ROS production while restoring Nrf2 expression. It prevented DNA damage and preserved mitochondrial membrane potential. The results also implicated increased mitochondrial fusion upon vit B3 treatment as seen by the elevated gene expression of Mfn1, Mfn2 and Opa1 and decreased fission as observed by the reduced expression of Fis1 and Drp1. The NADH levels were also seen to be rescued by vit B3 supplementation which translates to better energy production by the electron transport system. Additionally, vit B3 was observed to suppress inflammation and prevent muscle proteolysis by modulating an IKK/FoxO3a axis. Finally, vit B3 was able to improve differentiation as seen by the levels of MyoD and MyHC1 expression in the cells. Vit B3 acts in a multifaceted manner and reduces dex-induced skeletal muscle atrophy which is primarily a result of reduced oxidative stress and restored mitochondrial homeostasis. These findings highlight vit B3 as a potential therapeutic and nutritional supplement for maintaining the skeletal muscle health under myopathic conditions.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645264","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":"USF1 transcriptionally activates TRIM55 to promote diabetic cardiomyopathy progression by enhancing HSPB1 protein degradation.","authors":"Liu Huang, Cheng Zheng, Cuizhu He, Xiang Qiu, Huiqing Wei, Jie Yan, Kun Cui, Wenhui Yang, Lizhuo Yao, Yulian Wei, Xiaohong Nie, Bingyan Guo","doi":"10.1007/s10863-026-10107-z","DOIUrl":"10.1007/s10863-026-10107-z","url":null,"abstract":"<p><p>Background: Heat shock protein beta 1 (HSPB1) is confirmed to be a ferroptosis-related gene and plays an important role in the progression of diabetic cardiomyopathy (DCM). However, the specific functions and underlying molecular mechanisms of HSPB1 in DCM progression remain to be revealed. Methods: Cardiomyocytes were exposed to high glucose (HG) to mimic DCM cell models. The levels of HSPB1, tripartite motif-containing 55 (TRIM55), upstream stimulating factor 1 (USF1) and fibrosis-related markers were detected using western blot. Cell viability, apoptosis, inflammation, ferroptosis and mitochondrial membrane potential depolarization were assessed by CCK8 assay, flow cytometry, ELISA, corresponding kit and JC-1 staining. The interaction between TRIM55 and HSPB1 or USF1 was confirmed by Co-IP assay, ubiquitination assay, and dual-luciferase reporter assay. Diabetic mouse models were constructed by streptozotocin to assess the role of HSPB1 in vivo. Results: Overexpression of HSPB1 suppressed HG-induced cardiomyocyte apoptosis, ferroptosis, inflammation, mitochondrial dysfunction and fibrosis. TRIM55 enhanced the protein degradation of HSPB1 through ubiquitination, and the inhibitory effect of TRIM55 knockdown on HG-induced cardiomyocyte injury could be reversed by HSPB1 silencing. USF1 bound to TRIM55 promoter to activate its transcription. USF1 knockdown inhibited HG-induced cardiomyocyte injury by mediating the TRIM55/HSPB1 axis. In animal study, HSPB1 overexpression could improve cardiac function, alleviate inflammation and fibrosis in diabetic mouse models. Conclusion: The USF1/TRIM55/HSPB1 axis proposed in this study provides a potential molecular target for the treatment of DCM.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645215","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":"Mechanism of platelet-rich plasma inhibiting inflammatory response, oxidative stress, and senescence in synovial fibroblasts of patients with knee osteoarthritis via UBE2C based on transcriptome sequencing analysis.","authors":"Lili Zou, Yujuan Ma, Mingxian Hu, Zhenshuang Sun, Zhijun Shi, Jiahuan Gao, Xiguo Cai","doi":"10.1007/s10863-026-10105-1","DOIUrl":"10.1007/s10863-026-10105-1","url":null,"abstract":"<p><p>BACKGROUND: The incidence of knee osteoarthritis (KOA) continues to rise with the aging of the population, which seriously reduces the quality of life of patients. Platelet-rich plasma (PRP), a biological agent rich in growth factors and cytokines, has shown promising potential in the treatment of KOA in recent years. However, the specific molecular mechanism of its regulation of the pathological process is not clear. METHODS: Based on the GSE157364 dataset, DESeq2 software was used to analyze the differentially expressed genes (DEGs) of OA-FLSs between the PRP group and the Ctrl group. KEGG pathway and GO function enrichment analysis were performed by SangerBox. The genes related to cell senescence, inflammatory response and oxidative stress were screened from the GeneCards database, and the intersection was obtained by a Venn diagram. RESULTS: 911 DEGs (398 upregulated and 513 downregulated) were screened out. The expression of the key gene UBE2C in OA-FLSs was significantly downregulated compared with that in N-FLSs. PRP treatment significantly upregulated UBE2C expression in OA-FLSs, inhibited pro-inflammatory cytokine secretion, reduced intracellular ROS levels and β-Gal-positive senescent cell numbers, restored mitochondrial membrane potential, and downregulated the senescence-related proteins P21, P16, and P53. CONCLUSION: PRP can inhibit the inflammatory response, oxidative stress injury, and cell senescence of OA-FLSs by upregulating the expression of UBE2C, thereby delaying the pathological process of KOA, which provides a new molecular target and theoretical basis for the clinical treatment of KOA. </p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521011","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":"Ferulic acid relieves hypoxic damage by inhibiting endoplasmic reticulum stress, oxidative stress, and apoptosis through activating FOXA2-modulated Nrf2/HO-1 pathway in spermatogonial cells.","authors":"Weiwei Li, Xiurong Yin, Nan Zhang, Shihao Li, Chengmin Gu","doi":"10.1007/s10863-026-10104-2","DOIUrl":"10.1007/s10863-026-10104-2","url":null,"abstract":"<p><p>Male infertility is a global public health problem affecting human development. Ferulic acid (FA) is an important active phenolic substance that has been found to exert a protective effect on male reproductive system. Here we aimed to investigate the effect of FA on hypoxia-induced spermatogenesis damage and explore the underlying mechanisms. Mouse spermatogenic GC-1 spg cells were cultured under hypoxic conditions to establish an in vitro model of spermatogenesis damage. The small interfering RNAs targeting Forkhead Box A2 (FOXA2) were transfected into GC-1 spg cells to construct FOXA2-silencing cells. Cell counting kit-8 (CCK-8) and flow cytometry assays were performed to detect cell viability and apoptosis, respectively. Western blot analysis was conducted to examine the expression levels of related proteins. We found that FA improved the decreased cell viability of GC-1 spg cells under hypoxic conditions. FA attenuated hypoxia-induced endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis in GC-1 spg cells. Both mRNA and protein levels of FOXA2 were reduced after hypoxia induction, which were reversed by FA treatment. Knockdown of FOXA2 reversed the inhibitory effects of FA on ER stress, oxidative stress, and apoptosis in hypoxia-exposed GC-1 spg cells. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) overexpression restored the role of FOXA2 knockdown in FA-treated GC-1 spg cells under hypoxic conditions. Overall, we demonstrated the inhibitory effect of FA on hypoxia-induced ER stress, oxidative stress, and apoptosis in mouse spermatogenic GC-1 spg cells. Furthermore, FOXA2-mediated Nrf2 signaling contributed to the protective effects of FA against hypoxia-induced spermatogenesis damage. These findings suggest that FA may have the potential to ameliorate hypoxia-induced spermatogenesis injury.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"58 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512450","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":"Epigenetic activation of PDLIM7 via H3K27 acetylation mitigates neuroinflammation and neurodegeneration in parkinson's disease models.","authors":"Xinru Zhang, Zengwei Yin","doi":"10.1007/s10863-026-10088-z","DOIUrl":"10.1007/s10863-026-10088-z","url":null,"abstract":"<p><p>This study investigates the role and regulatory mechanisms of PDZ and LIM domain protein 7 (PDLIM7) in the pathology of Parkinson’s disease (PD) and evaluates its potential as a therapeutic target, specifically focusing on epigenetic regulation through histone acetylation. We investigated PDLIM7 expression and regulatory mechanisms in PD using a multi-level strategy that combined bioinformatics analysis, postmortem human substantia nigra tissues, and 6-hydroxydopamine (6-OHDA)-induced PD models in mice and cell lines. Utilizing functional tests, such as immunohistochemistry (IHC), ubiquitination analysis, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), and immunofluorescence (IF), the epigenetic and post-translational regulation of PDLIM7 was examined. Motor behavior was assessed using rotarod and pole tests. Additionally, we evaluated the therapeutic potential of N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxybenzamide (CTPB), a histone acetyltransferase (HAT) activator, in modulating PDLIM7 expression and attenuating neuroinflammatory responses, both in vitro and in vivo. PDLIM7 was remarkably downregulated in PD tissues and models. Overexpression of PDLIM7 mitigated α-synuclein aggregation, restored tyrosine hydroxylase (TH) expression, reduced glial activation as shown by IHC and IF markers including TH and glial fibrillary acidic protein (GFAP), and improved motor performance in 6-OHDA-lesioned mice. Mechanistically, histone H3 lysine 27 acetylation (H3K27ac) mediated by cyclic AMP response element-binding protein (CBP)/p300 regulated PDLIM7 transcription, and CTPB treatment enhanced PDLIM7 expression and rescued neuronal apoptosis and PD phenotypes. Furthermore, PDLIM7 promoted the ubiquitination and degradation of p65, suppressing nuclear factor kappaB (NF-κB)-driven expression of pro-inflammatory cytokines including interleukin (IL)-6 and IL-1β, and thereby attenuating neuroimmune dysregulation. PDLIM7 acts as an epigenetic-immune regulator in PD by linking H3K27ac to NF-κB inhibition. Targeting the CBP/p300-H3K27ac-PDLIM7 pathway may alleviate neuroinflammation and deficiencies in motor skills in PD.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512430","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":"Efficacy of 5-fluorouracil and metronomic chemotherapy mediated ornithine decarboxylase antizyme for inhibiting of colorectal cancer.","authors":"Qingwei Zou, Xiaolong Chen, Qing Liu, Dong Xia, Lin Gui","doi":"10.1007/s10863-026-10099-w","DOIUrl":"10.1007/s10863-026-10099-w","url":null,"abstract":"&lt;p&gt;&lt;p&gt;the inhibitory therapy for colorectal cancer (CRC) is currently a hot topic in clinical research, and the stability between ornithine decarboxylase antienzyme (OAZ) and polyamine has a regulatory effect on normal cell growth. 5-fluorouracil (5-FU) can up-regulate the expression efficiency of OAZ. It was to explore molecular mechanism and expression of 5-FU-mediated OAZ inhibition of the development of CRC, and to compare the mediation effect of 5-FU and uracil, providing a research basis for CRC therapy. A CRC mouse model was established using the colon adenocarcinoma cell line CT-26. After successful modeling, 96 mice were randomly divided into three groups: the control group (CG) received saline as a placebo; group G1 received conventional 5-FU chemotherapy (20 mg/m2, 3 times per week); and group G2 received low-dose, continuously administered metronomic 5-FU chemotherapy (500 mg/m2, once daily). All treatments lasted for eight weeks. Initially, there were 32 mice per group. After treatment, 15 mice from each group were used to compare OAZ programmed ribosomal frameshifting expression activity, polyamine levels, tumor cell inhibitory effects, and adverse reactions (ARs). The remaining mice were maintained under standard housing conditions for continued observation until twelve weeks post-treatment to record long-term survival and tumor recurrence. After treatment, OAZ protein content was increased, and the OAZ protein content ((0.112 ± 0.0045), (0.143 ± 0.005)) and positive expression rate (88.96%, 90.23%) in groups G1 and G2 were higher than those in CG (0.069 ± 0.0035, 70.21%) (P &lt; 0.05). The increase levels of OAZ (0.069 ± 0.0035) and OAZ programmed ribosomal frameshift (102 ± 10.61) in CG were lower than those in groups G1 and G2 (P &lt; 0.05). Western blot and RT-qPCR results further demonstrated that, compared to the CG, the protein and mRNA expression levels of the OAZ downstream target ODC, as well as the ribosomal proteins RPL10 and RPS6, were significantly downregulated in both the groups G1 and G2 (all P &lt; 0.05). After treatment, polyamine levels decreased in all three groups, but more dramatically in groups G1 and G2 than CG (P &lt; 0.05). Furthermore, the total effective rate (TER)of Group G1 and Group G2 was much higher than that of CG (80%, 86.67% vs. 46.67%),and the TER of Group G2substantially surpassed that of Group G1 (P &lt; 0.05).AR incidence in Group G2 (6.67%) was lower than that in Group G1 (46.67%) (P &lt; 0.05).Long-term follow-up results indicated that the group G2 exhibited the longest median survival time and the lowest tumor recurrence rate. As a classical chemotherapeutic agent, 5-FU inhibits CRC progression by enhancing OAZ programmed ribosomal frameshifting efficiency and reducing intracellular polyamine levels. Compared with conventional chemotherapy, the metronomic 5-FU regimen demonstrated improved safety and efficacy in the preclinical model, with reduced toxic side effects, suggesting potentially superior patient","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486001","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":"Coenzyme Q10 exerts anti-cancer effects in bladder cancer by inducing ROS-mediated apoptosis and autophagy.","authors":"Yebo Wang, Aimin Zhang, Hang Che, Jingyu Gao, Liping Zhao, Zhao Wang, Zijing Luo, Zhe Xu","doi":"10.1007/s10863-026-10093-2","DOIUrl":"10.1007/s10863-026-10093-2","url":null,"abstract":"<p><p>Bladder cancer (BCa) is one of the most common types of cancer that impacts the urinary system, and its incidence is increasing worldwide. Coenzyme Q10 (CoQ10) is a naturally occurring fat-soluble quinone with anti-oxidant and anti-inflammatory properties, and it plays a significant role in the suppression of tumor growth. Our objective was to elucidate the potential molecular mechanisms by which CoQ10 affects the advancement of BCa. In our study, human BCa cells 5637 and T24 and normal ureteral epithelial cells SV-Huc-1 were treated with different concentrations of CoQ10. Cell viability, reactive oxygen species (ROS) levels, apoptosis rate, and autophagy levels were assessed by CCK-8 assay, ROS assay kits, flow cytometry, reverse transcription quantitative PCR (RT-qPCR), and western blot analysis. Additionally, xenograft mouse models were conducted to investigate tumor growth. Our data indicated that CoQ10 decreased the viability of 5637 and T24 cells in a concentration- and time-dependent manner, while having minimal impact on SV-Huc-1 cells. Functional experiments uncovered that CoQ10 suppressed cell proliferation, and increased ROS levels, apoptosis, and autophagy in BCa cells. The application of the ROS inhibitor N-Acetyl-L-cysteine (NAC) significantly mitigated these effects. Furthermore, CoQ10 was found to block the Keap1-Nrf2 pathway, whereas the activator of Nrf2 (tert-Butylhydroquinone, TBHQ) and the agonist of HO-1 (Hemin) partially reversed CoQ10-induced ROS accumulation, apoptosis, and autophagy. In the BCa mouse model, CoQ10 inhibited tumor growth, apoptosis, autophagy, and the Keap1-Nrf2 pathway. These findings demonstrated that CoQ10 could be a therapeutic agent for BCa by promoting ROS-mediated apoptosis and autophagy via the Keap1-Nrf2 pathway.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486017","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":"METTL16-mediated m6A modification of LYRM2 drives breast cancer progression by inducing CD8⁺ T cell dysfunction via Glycolysis.","authors":"Mao Li, Haipeng Shen, Tianya Zhang, Xin Jin, Gaopei Jin, Yihao Cai","doi":"10.1007/s10863-026-10100-6","DOIUrl":"10.1007/s10863-026-10100-6","url":null,"abstract":"<p><p>CD8+ T cells in the tumor microenvironment suppress breast cancer (BRCA) progression. Although LYRM2 correlates with immune cell infiltration, its crosstalk mechanism with CD8+ T cells in BRCA remains unclear. We integrated bioinformatics, clinical samples, and cellular experiments to analyze the potential role of LYRM2 in BRCA and CD8+ T cell infiltration. In a co-culture system of BRCA cells and CD8+ T cells, lactate dehydrogenase release assay, carboxyfluorescein succinimidyl ester proliferation assay, and ELISA assessed CD8+ T cell cytotoxicity and proliferation. Colony formation, WB, and Transwell assays evaluated BRCA cell malignant phenotypes. GSEA identified LYRM2-regulated pathways. Seahorse XFe96 Analyzer and assay kits measured glycolysis parameters. Bioinformatics analysis predicted regulator proteins of LYRM2 m6A modification; RNA pull-down, RIP, MeRIP-qPCR and RNA stability assay validated binding specificity and methylation levels. A mouse allograft tumor model was established to evaluate CD8+ T cell infiltration and BRCA progression in vivo. In BRCA, overexpressed LYRM2 correlated with poorer prognosis and decreased CD8+ T cell infiltration. Knocking down LYRM2 enhanced CD8+ T cell antitumor activity and inhibited the malignant progression of BRCA cells. METTL16-mediated m6A modification of LYRM2 suppressed CD8+ T cell function by reshaping glucose metabolism, thereby promoting BRCA progression. In vivo, the METTL16/LYRM2 axis weakened CD8+ T cell function and accelerated tumor growth. METTL16 promotes stable expression of LYRM2 via m6A methylation, thereby activating glycolysis pathways to induce CD8+ T cell dysfunction, which finally drives BRCA progression. The finding identified LYRM2 as a potential target for BRCA immunotherapy.</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":"147480815","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":"The eIF3a/m6A/ENO1 axis orchestrates glycolytic reprogramming and cell growth in cervical cancer.","authors":"Riyangul Kurban, Jing Pan, Tusunggu Amar, Xiaoli Bo","doi":"10.1007/s10863-026-10096-z","DOIUrl":"10.1007/s10863-026-10096-z","url":null,"abstract":"<p><p>Glycolysis plays a key role in the development of cervical cancer (CC); therefore, investigating its molecular mechanisms is crucial for the development of new therapies targeting CC. In this study, we identified an eukaryotic translation factor 3a (eIF3a)-N6 methyladenosine (m6A)-alpha enolase (ENO1) regulatory axis responsible for glycolysis of CC. Specifically, through bioinformatics analysis, RT-PCR, and western blot assays, eIF3a was identified as a prognosis biomarker in CC. By performing CCK-8 method and flow cytometry technique, we demonstrated that silencing eIF3a in Caski cells decreased proliferation, induced cell cycle arrest at the G0/G1 phase, and increased apoptosis, while overexpression in Hela cells had the opposite effects. eIF3a overexpression also accelerated glycolysis in CC cells, as evidenced by increased glucose uptake, lactate production, and ATP generation. ENO1 was found to be up-regulated at the protein level by eIF3a, and its mRNA was enriched for m6A modifications. Knockdown of YTH domain family, member 3 (YTHDF3) or methyltransferases reduced ENO1 mRNA binding to eIF3a, down-regulating ENO1 protein expression. The functional recovery assays showed that modulating the eIF3a/ENO1 axis altered CC cell growth. Altogether, eIF3a promotes ENO1 translation to accelerate glycolysis in an m6A-dependent manner, thus promoting cell proliferation and cell cycle progression, and inhibiting apoptosis in CC cells.</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":"147480841","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}