Molecular and Cellular Biochemistry最新文献

{"title":"LNA GapmeR silencing of KRAS G12V impairs growth and function in SW480 cells.","authors":"Joudi Feras Khudeir, Abdelaziz Tlili","doi":"10.1007/s11010-026-05545-7","DOIUrl":"https://doi.org/10.1007/s11010-026-05545-7","url":null,"abstract":"<p><p>Activating mutations in the KRAS oncogene, particularly the G12V substitution, are key drivers of tumorigenesis and therapeutic resistance across multiple cancer types. However, direct pharmacological inhibition of mutant KRAS has remained a major clinical challenge due to its structural and biochemical properties. In this study, we employed a chemically modified locked nucleic acid (LNA) GapmeR antisense oligonucleotide specifically designed to target the KRAS G12V transcript. The SW480 cell line was used as a representative in vitro model. Assays conducted were Quantitative RT-PCR, luciferase reporter assay using a KRAS representative construct, MTT assay, wound-healing assay, Annexin V-FITC apoptosis assay, and cell cycle distribution. RT-qPCR confirmed a marked reduction in KRAS mRNA levels. Luciferase reporter assay provided further evidence of GapmeR-mediated suppression at the transcript level. MTT revealed a robust cytotoxic effect at 100 nM, sufficient to induce significant cancer cell death while sparing normal cells. Scratch assay demonstrated increased scratch area, along with morphological changes. Apoptosis assay revealed a pronounced induction of late apoptosis and necrosis. Cell cycle analysis indicated disruption of the cell cycle. Our findings establish evidence that transcript level targeting of KRAS G12V using GapmeRs is associated with functional alterations in SW480 cells, warranting further validation in additional cancer models and in vivo studies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIRA promotes osteogenic differentiation of BMSCs and ameliorates osteoporosis by mediating M2 polarization of macrophages through the YAP1/β-catenin pathway.","authors":"Yi Hou, Yunfei Li, Ke Liu, Ganggang Zhai, Xiaming Liang, Jia Zheng","doi":"10.1007/s11010-026-05553-7","DOIUrl":"https://doi.org/10.1007/s11010-026-05553-7","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP7-stabilized CEBPB promotes HpSCC progression by upregulating IL6 to activate the JAK2/STAT3 signaling.","authors":"Honghui Li, Rong Fan, Yiping Qu, Yuan Shao, Yanxia Bai, Chongwen Xu, Jinsong Hu, Xiaozhi Zhang","doi":"10.1007/s11010-026-05557-3","DOIUrl":"https://doi.org/10.1007/s11010-026-05557-3","url":null,"abstract":"<p><strong>Background: </strong>CCAAT/enhancer-binding protein B (CEBPB) has been reported as a transcription factor implicated in the occurrence and development of various human tumors. However, its role and mechanism in hypopharyngeal squamous cell carcinoma (HpSCC) remain unclear.</p><p><strong>Methods: </strong>qRT-PCR, western blot, and immunohistochemistry assays were used for mRNA or protein expression in HpSCC tissus or cells. HpSCC cell phenotypes were evaluated using colony formation, EdU, wound healing, and transwell assays. The role of CEBPB in HpSCC tumorigenesis was also investigated by establishing xenograft model in mice. Interaction between CEBPB and ubiquitin-specific peptidase 7 (USP7) was confirmed using co-immunoprecipitation (Co-IP), cycloheximide (CHX) chase, and deubiquitination assays. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were employed to determine the transcription regulation of CEBPB on IL-6.</p><p><strong>Results: </strong>Higher CEBPB expression was found in HpSCC tissues and represented a worse prognosis. Knockdown of CEBPB inhibited HpSCC cell proliferation, migration, invasion, and EMT, while overexpression of CEBPB displayed the opposite trend. USP7 stabilized CEBPB protein by its deubiquitination activity. CEBPB binds to the promoter of IL-6 to increase its transcription, thus activating the JAK2/STAT3 signaling pathway. Furthermore, USP7 could promote IL-6 expression through CEBPB. Functionally, restoration of CEBPB expression reversed the anti-cancer effect of USP7 depletion in HpSCC. Moreover, the inhibitory effect of HpSCC progression mediated by CEBPB knockdown was abated upon IL-6 upregulation.</p><p><strong>Conclusion: </strong>Our finding reveals a novel USP7/CEBPB/IL-6/JAK2/STAT3 axis in regulating HpSCC progression, targeting this pathway might be a valuable strategy for HpSCC therapy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.","authors":"Mohamed A Raafat, Shaker Al-Hasnaawei, Hayjaa Mohaisen Mousa, Malathi Hanumanthayya, Samir Sahoo, S Prathiba, Gurjant Singh, Aashna Sinha","doi":"10.1007/s11010-026-05542-w","DOIUrl":"https://doi.org/10.1007/s11010-026-05542-w","url":null,"abstract":"<p><p>Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, remain leading causes of disability and premature death. Although they present with distinct clinical phenotypes, they converge on several pathogenic processes. Among these, mitochondrial dysfunction has emerged as a key driver of neurodegeneration, encompassing impaired bioenergetic capacity, disturbed calcium handling, altered mitochondrial dynamics, insufficient mitophagy, and excessive production of reactive oxygen species (ROS). This review provides a focused synthesis of the ways in which mitochondrial pathology contributes to neurodegeneration across major neurodegenerative disorders and summarizes therapeutic strategies designed to target mitochondria. We outline disease-relevant mitochondrial abnormalities and connect them to neuronal loss, synaptic failure, and neuroinflammatory cascades, with particular attention to mitochondrial ROS and inflammatory signaling linked to mitochondrial DNA. The manuscript further evaluates current and emerging interventions, including mitochondria-targeted antioxidants, mitochondrial transfer/transplantation, exercise, dietary approaches, and nanotechnology-enabled delivery systems. For each strategy, we consider the mechanistic rationale, key preclinical findings, and barriers to translation. Across experimental models, many of these approaches confer measurable neuroprotection-often reflected by lower oxidative burden, stabilization of mitochondrial membrane potential, and partial restoration of ATP production. However, clinical findings have been inconsistent, suggesting that efficacy depends strongly on disease stage, patient heterogeneity, and the specific mitochondrial defect being targeted. By integrating mechanistic insights with therapeutic evidence, this review offers a structured perspective on shared and disease-specific features of mitochondrial dysfunction and highlights priorities for advancing mitochondria-centered interventions toward meaningful clinical benefit.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of sepsis-associated acute kidney injury by ELAVL1 through USP14/NCOA4-mediated ferroptosis in renal tubular epithelial cells.","authors":"Xiaoliang Zhu, Peihuan Zheng, Huihui Jin, Qian Zhao, Kaimin Kong, Lei Zheng, Xiaoqiong Huang, Ming Zheng","doi":"10.1007/s11010-026-05533-x","DOIUrl":"https://doi.org/10.1007/s11010-026-05533-x","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.","authors":"Kewei Fu, Mengfei Cao, Yinyu Wang, Jie Luo, Wei Yuan","doi":"10.1007/s11010-026-05540-y","DOIUrl":"https://doi.org/10.1007/s11010-026-05540-y","url":null,"abstract":"<p><p>Fibrosis, a critical global health challenge, is primarily characterized by pathological scar formation due to an imbalance in tissue injury repair mechanisms, ultimately leading to progressive organ dysfunction. Notably, the Yes-associated protein (YAP), a central effector molecule in the Hippo signaling pathway, serves as a pivotal molecular regulator across fibrotic processes in multiple organs. Aberrant YAP activation is a hallmark of fibrosis in multiple organs, including the liver, kidney, heart, and lung, where it drives pro-fibrotic gene expression. Although basic research has highlighted YAP's essential role in fibrotic diseases, translating these insights into clinical applications remains complex. The current repertoire of targeted therapeutic options for fibrosis is restricted, further complicated by variations in tissue-specific responses to YAP modulation. This highlights the urgent need for a thorough analysis of the YAP regulatory network. In this review, we analyze the YAP protein interaction network to clarify the dynamic regulation of its nuclear-cytoplasmic trafficking. Furthermore, we explore the distinct signaling characteristics of YAP during organ fibrosis, summarize recent developments in anti-fibrotic strategies targeting YAP, and assess the translational potential of intervening in YAP and its upstream and downstream pathways for effective anti-fibrotic therapy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: METTL5 promotes tumor progression and ferroptosis resistance via MGST1 in HCC.","authors":"Tao Ji, Xiangzhuo Miao, Yinghao Fang, Jianmin Nie, Qing Zhu, Pengyu Zhu, Wei Liao, Dinghua Yang","doi":"10.1007/s11010-026-05539-5","DOIUrl":"https://doi.org/10.1007/s11010-026-05539-5","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of NCOA4-mediated ferritinophagy improves cardiac remodeling in diabetic cardiomyopathy via MITOL/parkin signaling.","authors":"Linhe Lu, Yang Liu, Yalan Shao, Xiang Xiong, Mengen Zhai, Jian Yang, Lifang Yang","doi":"10.1007/s11010-026-05513-1","DOIUrl":"https://doi.org/10.1007/s11010-026-05513-1","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition caused by unfavorable myocardial sequelae, with more severe cardiac dysfunction observed in patients with diabetes than in those without diabetes. Recently, ferroptosis has been implicated in DCM; however, its role in DCM remains incompletely elucidated. This study was conducted to examine the impact of mitochondrial ubiquitin ligase (MITOL/March5) and the mitophagy receptor Parkin on DCM-induced cardiac dysfunction, as well as the effect of ferritinophagy. Wild-type and db/db mice were fed normal chow or a high-fat diet and subjected to streptozotocin treatment. Cardiac geometry and function, as well as ferroptosis-related biomarkers, were assessed upon completion of experiments. Our findings revealed that DCM induced notable alterations in cardiac geometry by increasing myocardial fibrosis and ferroptosis, involving increased reactive oxygen species production and lipid accumulation. Nuclear receptor coactivator 4 (NCOA4)-related ferroptosis was significantly activated, whereas Parkin-dependent mitophagy was dramatically inhibited. However, adeno-associated virus (AAV)-MITOL treatment markedly attenuated cardiac dysfunction and ferroptosis with those in the DCM group. Furthermore, Ad Parkin alleviated NCOA4-mediated ferroptosis and suppressed myocardial apoptosis compared with those in the high-glucose/high-fat group. Our in vitro analysis demonstrated that MITOL inhibition compromised cardiomyocyte function and elicited mitochondrial injury and lipid peroxidation, the effects of which were negated by Parkin activation. This study underscores the pivotal protective role of the MITOL/Parkin signaling pathway against DCM-induced cardiac dysfunction in NCOA4-mediated ferritinophagy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of EMT and cholangiocarcinoma metastasis by KIN17 through the mTOR signaling pathway.","authors":"Yuxia Yang, Qianying Luo, Chuhong Huang, Xiaocong Lin, Lok Ting Chu, Qiuyan Li, Jinjing Tang, Tao Zeng","doi":"10.1007/s11010-026-05531-z","DOIUrl":"https://doi.org/10.1007/s11010-026-05531-z","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pro-inflammatory LPS drives production and release of the chemokine MCP-1 in human coronary artery smooth muscle cells.","authors":"Elisabeth Bankell, Olof Gidlöf, Bengt-Olof Nilsson","doi":"10.1007/s11010-026-05532-y","DOIUrl":"https://doi.org/10.1007/s11010-026-05532-y","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}