International Journal of Biological Sciences最新文献

{"title":"CREB Regulates Cisplatin Resistance by Targeting TNKS and KDM6A in NSCLC cell-Derived Tumor Spheroid.","authors":"Ji Hae Lee, Youngjoo Kwon, Kyungsil Yoon","doi":"10.7150/ijbs.109419","DOIUrl":"https://doi.org/10.7150/ijbs.109419","url":null,"abstract":"<p><p>Platinum-based chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC); however, innate and acquired resistance is a major obstacle. To determine the transcriptional regulators of resistance, we first classified three-dimensional tumor spheroids derived from 11 NSCLC cell lines into cisplatin-sensitive or -resistant groups based on their cisplatin sensitivity and selected signature genes that were differentially altered between the groups. Using reverse engineering methods and functional validation, cAMP response element-binding protein 1 (CREB) was identified as a major regulator of cisplatin resistance. Among the putative target genes of CREB responsible for cisplatin resistance, cisplatin treatment significantly decreased the occupancy of CREB in the regulatory regions of <i>TNKS</i> and <i>KDM6A</i> in cisplatin-sensitive cells, but not in resistant cells, resulting in decreased expression of these protein in the sensitive group. Furthermore, CREB knockdown led to increased sensitivity to cisplatin with reduced levels of TNKS and KDM6A in both cisplatin-resistant tumor spheroids and tumors in a xenograft mouse model. In conclusion, our study delineates the role of CREB in cisplatin resistance and suggests that CREB inhibition is a potential therapeutic strategy for cisplatin-resistant NSCLCs.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4851-4871"},"PeriodicalIF":10.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate metabolic reprogramming and histone lactylation modification in sepsis.","authors":"Ji Zhang, Dan Wu, Fu Zeng, Haiyun Gu, Chengbao Li, Juan P Cata, Kefang Guo, Changhong Miao, Hao Zhang","doi":"10.7150/ijbs.116088","DOIUrl":"https://doi.org/10.7150/ijbs.116088","url":null,"abstract":"<p><p>Sepsis, a serious condition characterized by life-threatening organ dysfunction owing to infection, lacks specific therapeutic interventions. Lactate serves as a crucial biomarker in sepsis, reflecting both the patient's metabolic state and the severity of the condition. Lactylation, the process whereby lactate is conjugated to lysine residues in proteins, profoundly alters protein structure and function. This review delves into the crucial roles of lactate and lactylation within the septic environment, illuminating the intricate feedback loop between metabolic reprogramming and lactylation in sepsis. Herein, fluctuations in lactate levels influence patterns of lactylation, which subsequently regulate energy metabolism. Lactylation is essential for modulating immune responses, adjusting gene expression profiles in immune cells, and shifting the balance between pro-inflammatory and anti-inflammatory pathways. The discovery of these pathways has significant implications for development of targeted therapies against sepsis. Furthermore, this review addresses the advancements and current limitations associated with lactylation research methodologies, and proposes new directions for future research. Overall, this narrative underscores the transformative potential of lactylation in understanding and managing sepsis, advocating for a multidisciplinary approach to unravel the complex interplay between metabolic processes and epigenetic regulation in critical illnesses.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"5034-5055"},"PeriodicalIF":10.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of sphingosine-1-phosphate receptors can relieve myocardial ischemia-reperfusion injury by mitigating oxidative stress and ferroptosis in cardiomyocytes.","authors":"Xuan Xu, Runqian Li, Shengnan Li, Qin Wei, Fuchao Yu, Genshan Ma, Jiayi Tong","doi":"10.7150/ijbs.107402","DOIUrl":"https://doi.org/10.7150/ijbs.107402","url":null,"abstract":"<p><p><b>Background:</b> Myocardial ischemia/reperfusion (MI/R) injury remains a major challenge in cardiovascular therapeutics, with pathogenesis closely associated with reactive oxygen species (ROS) accumulation and ferroptosis. While sphingosine-1-phosphate receptors (S1PRs) activation demonstrates cardioprotective potential against MI/R injury, its mechanistic relationship with redox homeostasis and ferroptotic pathways requires elucidation. <b>Methods:</b> Using hypoxia/reoxygenation (H/R)-treated cardiomyocytes, we investigated S1P-mediated regulation of <i>Slc7a11</i>, <i>Gpx4</i>, and <i>MnSOD</i> transcription through pharmacological inhibition of the S1PRs/Src/STAT3 signaling pathway. Mechanistic insights into S1PRs/Src/STAT3-mediated transcriptional control were obtained through integrated bioinformatics, dual-luciferase reporter assays, chromatin immunoprecipitation, and molecular profiling (qRT-PCR/ Western blotting). In a MI/R mouse model, the therapeutic effects of S1P and Fingolimod were determined using echocardiography, TTC staining, fluorescent probes, and TEM, with mechanisms validated by Western blotting and qRT-PCR. <b>Results:</b> In vitro studies revealed that S1PRs activation (via S1P or Fingolimod) promoted STAT3 phosphorylation and nuclear translocation through Src signaling, thereby enhancing transcriptional upregulation of <i>Slc7a11</i>, <i>Gpx4</i>, and <i>MnSOD</i>. This signaling cascade attenuated H/R-induced ROS generation, mitochondrial damage, and ferroptosis markers, with S1PR1 demonstrating predominant cytoprotection. Chromatin studies confirmed p-STAT3 binding to antioxidant/ferroptosis-related gene promoters. In vivo findings mirrored cellular observations, showing S1PRs agonism significantly improved cardiac function, reduced infarct size, and suppressed myocardial lipid peroxidation compared with untreated controls. <b>Conclusions:</b> Our findings establish that S1PRs signaling confers cardioprotection against MI/R injury through STAT3 phosphorylation-mediated transcriptional activation of antioxidant defense systems and ferroptosis suppression. This mechanistic insight positions S1PRs modulation as a promising therapeutic strategy for ischemic cardiomyopathy.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"5079-5096"},"PeriodicalIF":10.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of SIRT3 in aging and aging-related diseases.","authors":"Yuzi You, Zhong Wang","doi":"10.7150/ijbs.115518","DOIUrl":"https://doi.org/10.7150/ijbs.115518","url":null,"abstract":"<p><p>Aging is an inexorable pathophysiological progression characterized by the overwhelming deterioration of tissue integrity and cellular function coupled with increased risks of various aging-related diseases. Demographic shifts toward extended longevity have precipitated a paradigm shift in disease epidemiology, in which neurodegenerative conditions and cardiovascular pathologies now constitute predominant determinants of morbidity and mortality in geriatric populations. These conditions severely erode functional autonomy in aging populations and strain healthcare infrastructures globally. As a principal nicotine adenine dinucleotide-dependent deacetylase within mitochondria, sirtuin 3 (SIRT3) exerts multimodal regulatory effects spanning mitochondrial bioenergetics, oxidative stress, and epigenetic modifications associated with aging. This review summarizes recent discoveries regarding the involvement of SIRT3 in physiological aging and its pathophysiological intersections with major aging-related disorders, providing new insights and ample inspiration for future research aimed at slowing the aging process and improving outcomes in aging-related diseases.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"5135-5163"},"PeriodicalIF":10.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation-mediated LncRNA CRAT40 promotes colorectal cancer progression by recruiting YBX1 to initiate RelA transcription.","authors":"Qing Lu, Xiuhe Lv, Jin Wang, Bihan Xia, Hailin Yan, Zhu Wang, Jinlin Yang","doi":"10.7150/ijbs.105629","DOIUrl":"https://doi.org/10.7150/ijbs.105629","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in the initiation and progression of various malignancies, including CRC. In this study, we found that lnc-CRAT40 was upregulated in CRC and associated with poor prognosis following CRC resection. Functional assays revealed that elevated lnc-CRAT40 expression promotes tumor cell proliferation and metastasis both in vitro and in vivo. The modification of N6-methyladenosine, driven by METTL3, was essential for the stability of lnc-CRAT40, which may partially contribute to the upregulation of lnc-CRAT40. Mechanistically, lnc-CRAT40 directly interacted with Y-box binding protein 1 (YBX1) and recruits it to the RelA promoter, thereby activating NF-κB signaling, which in turn drives CRC proliferation and metastatic potential. These findings provide novel insights into the molecular mechanisms underlying CRC progression and highlight lnc-CRAT40 as a potential prognostic biomarker and therapeutic target.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4834-4850"},"PeriodicalIF":10.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JCAD-Derived from Plasma Exosomes: Promoting Tumor Cell Progression and Predicting Poor Outcomes in Breast Cancer.","authors":"Douwaner Liu, Min Xiong, Xiaoting Chen, Xuliren Wang, Yuting Sang, Shiyang Liu, Liyi Zhang, Weiru Chi, Hengyu Ren, Bingqiu Xiu, Qi Zhang, Yayun Chi, Jiong Wu, Jingyan Xue","doi":"10.7150/ijbs.107763","DOIUrl":"https://doi.org/10.7150/ijbs.107763","url":null,"abstract":"<p><p><b>Background:</b> Breast cancer has the highest incidence among all cancers in women, and the prognosis of breast cancer is strongly linked to the stage of the disease. As one of the components found in liquid biopsy samples, exosomes are membranous vesicles that are actively secreted by living cells. Therefore, the key genes in exosomes may serve as biomarkers for predicting the prognosis of breast cancer patients. <b>Methods:</b> In this study, 128 blood samples collected from breast cancer patients at Fudan University Shanghai Cancer Center between June 2018 and March 2019 were subjected to transcriptome sequencing, and the resulting dataset was used as the training dataset. A LASSO regression model was employed for screening prognostic genes. Additionally, 131 patient samples from February 2020 to February 2022 were collected to establish the validation dataset. The corresponding phenotypes and mechanisms of the key genes were confirmed by CCK8 cell proliferation, colony formation, EdU cell proliferation, flow cytometry, transwell cell migration, scratch assay, animal study and RNA-seq assays. <b>Results:</b> Eleven differentially expressed genes tended to increase from the benign stage to the late stage of breast cancer. Five genes were further identified by LASSO regression analysis to establish a prognostic model. The time-dependent receiver operating characteristic (ROC) curves revealed area under the curve (AUC) values of 0.858 for the 1-year follow-up and 0.772 for the 2-year follow-up. The time-dependent ROC curve of the validation dataset indicated an AUC value of 0.840 for the 1-year follow-up. JCAD, a gene closely associated with prognosis, was selected for further investigation. The experimental results demonstrated that JCAD may activate the Wnt/β-catenin pathway by increasing FZD1 expression, thereby promoting the EMT process and breast cancer progression. <b>Conclusions:</b> Exosomal JCAD, as a prognostic marker, plays an important role in the diagnosis and treatment of breast cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4816-4833"},"PeriodicalIF":10.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Methyltransferase SETD1B Maintains Cancer Stem Cell Niche by Regulating the Crosstalk between CD24 and Surface Adhesion Molecules in Hepatocellular Carcinoma.","authors":"Yan Gao, Wei Zhou, Yuehong Gao, Shunxi Wang, Zhiling Xu, Xiao Xiang, Li Yang","doi":"10.7150/ijbs.112943","DOIUrl":"https://doi.org/10.7150/ijbs.112943","url":null,"abstract":"<p><p><b>Purpose:</b> Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a dismal prognosis that is largely attributed to the capacity of liver cancer stem cells (LCSCs) to self-renew in response to conventional therapies. Therefore, it is crucial to develop new therapeutic strategies that target LCSCs to improve the clinical outcomes of patients with HCC. <b>Experimental Design:</b> We surveyed and analyzed publicly available single-cell TCGA (the cancer genome atlas), single-cell (scRNA-seq) and spatial RNA-sequencing databases from HCC patient specimens for genes uniquely expressed in LCSCs. We generated and characterized LCSCs from patient-derived HCC cell lines and used them as tools to uncover the previously unknown molecular mechanisms associated with the stemness of LCSCs. We selectively screened a bank of natural compounds to identify drugs that can specifically target LCSCs for HCC treatment and documented their effects both <i>in vitro</i> and <i>in vivo</i>. <b>Results:</b> TCGA analyses showed that SETD1B expression was aberrantly elevated in HCC, correlating with poor prognosis and a distinct molecular signature of stemness. We demonstrated that SETD1B, driven by MAZ, enhances stem characteristics by promoting anchorage-independence, cellular adhesion, tumor sphere formation, and growth via the surface glycoprotein CD24. We identified triptolide (Trip), which serves as a potent suppressor of LCSC stemness by targeting SETD1B for degradation, thereby dramatically attenuating HCC progression <i>in vitro</i> and <i>in vivo</i>. <b>Conclusions:</b> These findings establish the MAZ/SETD1B/CD24 signaling cascade as a critical regulatory mechanism of LCSC stemness and highlight Trip as a potential therapeutic agent for HCC.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4798-4815"},"PeriodicalIF":10.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The function of GPCRs in different bone cells.","authors":"Yan Zhang, Nai-Ning Wang, Zi-Han Qiu, Jia-Hao Wang, Wen-Na An, Li-Dan Shi, Fei Chen, Da-Jin Zhang, Si-Yue Wang, Tie-Lin Yang, Shou-Ye Hu, Yan Guo","doi":"10.7150/ijbs.113585","DOIUrl":"https://doi.org/10.7150/ijbs.113585","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are recognized as critical therapeutic targets in bone disorders, owing to their multifaceted regulatory roles across diverse bone cell lineages. This review systematically catalogs GPCR expression and functional heterogeneity in key bone cells: 12 GPCRs in mesenchymal stem cells (MSCs) orchestrate lineage specification; 21 GPCRs in osteoblasts/osteocytes mediate matrix mineralization and mechanotransduction; 23 GPCRs in macrophages/osteoclasts regulate inflammatory bone resorption; 31 GPCRs in chondrocytes govern endochondral ossification and osteoarthritis pathogenesis; and 8 GPCRs in other cell types modulate bone-related physiological processes. By integrating canonical signaling axes-cAMP/PKA-dependent transcriptional networks, PLC-β/IP3-driven calcium signaling, and NF-κB-modulated immuno-skeletal interactions-we elucidate how GPCRs dynamically coordinate cellular plasticity to maintain skeletal homeostasis. This work establishes a multidimensional research framework integrating historical context, molecular mechanisms, and cutting-edge methodologies to advance GPCR-targeted therapies for bone-related diseases. Moreover, this review provides insights for clinical translation, including biased agonism and allosteric modulation precision strategies to restore skeletal equilibrium in osteoporosis, arthritis, and regenerative medicine.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4736-4761"},"PeriodicalIF":10.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sesamin Induces MCL-1-Dependent Apoptosis in Activated T Cells and Ameliorates Experimental Atopic Dermatitis.","authors":"Hee-Suk Park, Woo Jung Sung, Yoon-Yub Park, Jaewoo Hong, Hoon-Kyu Oh, Hyun-Su Lee","doi":"10.7150/ijbs.116753","DOIUrl":"https://doi.org/10.7150/ijbs.116753","url":null,"abstract":"<p><p>Sesamin, a natural lignan derived from <i>Sesamum indicum</i>, has been reported to possess anti-inflammatory and pro-apoptotic properties. However, its effect on T cell-mediated diseases and the underlying molecular mechanisms remain unclear. In this study, we demonstrate that sesamin selectively induces apoptosis in activated T cells through direct interaction with MCL-1, a critical anti-apoptotic protein of the Bcl-2 family. Sesamin suppressed IL-2 expression, CD69 upregulation, and proliferation in activated human and murine T cells. Molecular docking predicted strong binding of sesamin to the BH3-binding groove of MCL-1, which was validated by pull-down and co-immunoprecipitation assays. Sesamin inhibited MCL-1 phosphorylation at Ser64 and disrupted its heterodimerization with Bak, promoting caspase-3/8 cleavage and apoptotic death selectively in activated, but not resting, T cells. In a murine model of atopic dermatitis, oral administration of sesamin ameliorated pathological skin symptoms, reduced Th2/Th17 cytokine expression, serum IgE, mast cell infiltration, and lymph node hypertrophy. These effects correlated with suppressed MCL-1 activity and enhanced apoptosis in inflamed tissue. Our findings suggest that sesamin modulates immune responses via a novel MCL-1-dependent mechanism and represents a promising dietary-derived therapeutic strategy for T cell-driven chronic inflammatory diseases.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4719-4735"},"PeriodicalIF":10.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL16 Promotes Lipid Metabolic Reprogramming and Colorectal Cancer Progression.","authors":"Jie Li, Qian Luo, Minjie Lu, Chen Lu, Caihong Xu, Jie Ding, Tian Zhan, Jing Zhu, Mengsen Qian, Shuhui Lin, Lisha Chang, Juan Li, Keming Wang","doi":"10.7150/ijbs.105391","DOIUrl":"https://doi.org/10.7150/ijbs.105391","url":null,"abstract":"<p><p><b>Background:</b> Lipid reprogramming represents a pivotal stage in tumor progression. N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, plays a significant role in colorectal cancer (CRC) development, though its specific involvement in lipid reprogramming remains unclear. <b>Methods:</b> Bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases revealed differential expression of METTL16 (M16), which was further validated through qRT-PCR and Western blotting in CRC tissues and cell lines. The impact of M16 on CRC proliferation, metastasis, invasion, and lipid reprogramming was evaluated using both <i>in vivo</i> and <i>in vitro</i> approaches. Regulatory mechanisms underlying M16's role in CRC progression were explored using immunofluorescence (IF) staining, RNA immunoprecipitation (RIP), MERIP assay, RNA pull-down assay, total m6A measurement, RNA stability assay, protein stability analysis, and luciferase reporter assays. <b>Results:</b> Analysis results demonstrated a significant upregulation of the m6A methyltransferase METTL16 in CRC, closely associated with poor prognosis and abnormal lipid droplet accumulation. Functional assays revealed that M16 overexpression markedly promotes CRC cell proliferation, migration, and invasion both <i>in vitro</i> and <i>in vivo</i>, primarily by enhancing lipid reprogramming. Mechanistically, M16 induces m6A modification of TM7SF2 mRNA, stabilizing it via an IGF2BP1- and IGF2BP2-dependent pathway, thereby upregulating TM7SF2 expression and driving lipid reprogramming in CRC. <b>Conclusion:</b> In conclusion, these findings highlight the critical role of the M16/m6A/TM7SF2 axis in lipid metabolic reprogramming in CRC, offering potential therapeutic targets for its treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 11","pages":"4782-4797"},"PeriodicalIF":10.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}