JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Smurf2 Suppresses Proliferation and Cell Cycle of Triple-Negative Breast Cancer Cells by Promoting the Polyubiquitination and Degradation of RPL35A","authors":"Siyu Wei,&nbsp;Yuying Liu,&nbsp;Zhihao Wang,&nbsp;Ti Wei,&nbsp;Wenkai Zhou,&nbsp;Wanwan Li,&nbsp;Jiaxin Zhang,&nbsp;Zhiyi Liu,&nbsp;Zhao Liu","doi":"10.1111/jcmm.70394","DOIUrl":"10.1111/jcmm.70394","url":null,"abstract":"<p>Human L35a ribosomal protein (RPL35A) has been reported to confer higher drug resistance and viability to triple-negative breast cancer (TNBC) cells, but the mechanism related to its promotion of TNBC malignant progression is still unclear. Here, we found that silencing of RPL35A could inhibit the proliferation of TNBC cells by suppressing the G1/S phase transition. Furthermore, SMAD-specific E3 ubiquitin protein ligase 2 (Smurf2) was found to be a potential upstream ubiquitin ligase of RPL35A. Smurf2 could interact with RPL35A and promote its degradation and K63-linked polyubiquitination, thereby suppressing the G1/S phase transition and proliferation of TNBC cells. In addition, the roles of Smurf2 were confirmed in a xenograft mouse model. Finally, we found a negative correlation between the protein levels of RPL35A and Smurf2 in human TNBC tissues. In summary, Smurf2 inhibits the proliferation of TNBC cells by blocking the cell cycle process, which is associated with regulating RPL35A.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted Analysis of Lactobacillus plantarum DMR14 Reveals Promising Antidiabetic Properties Through In Vivo Assays and Molecular Simulations","authors":"Shirmin Islam,&nbsp;Suvro Biswas,&nbsp;Md. Ariful Islam,&nbsp;Jui Biswas,&nbsp;Amit Kumar Dutta,&nbsp;Golam Gaus Mohiuddin,&nbsp;Md. Abu Saleh,&nbsp;Shahriar Zaman","doi":"10.1111/jcmm.70347","DOIUrl":"10.1111/jcmm.70347","url":null,"abstract":"<p>Due to the growing concern about diabetes worldwide, we investigated the antidiabetic potential of <i>Lactobacillus plantarum</i> DMR14, assessing its effects on the diabetic mice and identifying safe, bioactive compounds targeting DPP4 protein for drug development through various methods, including in vivo assays, GC–MS analysis and molecular docking simulations. The animal experiments showed that after 3 weeks of treatment, the blood sugar levels of mice given the bacteria were reduced by 35.03% compared to baseline. The treatment also significantly lowered blood lipids such as triglycerides, total cholesterol and LDL cholesterol, but did not affect HDL cholesterol levels. Additionally, we identified three compounds that effectively targeted a protein (DPP4) involved in diabetes (PDB ID: 4A5S). These compounds were predicted to be safe for absorption, processing and elimination by the body, and showed no signs of inducing cancer in computer simulations. Further simulations indicated that these compounds bind stably to the protein over time. Diabetic mice treated with <i>Lactobacillus plantarum</i> DMR14 exhibited improved organ health, reduced glucose levels and better metabolic markers. Computer analysis suggested compounds that could enhance enzyme inhibition, indicating potential antidiabetic properties in this strain. These suggested compounds could be considered potential candidates for developing antidiabetic drugs.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stromal Cell Derived Factor-1 Promotes Hepatic Insulin Resistance via Inhibiting Hepatocyte Lipophagy","authors":"Chunfeng Lu,&nbsp;Yuting Zhang,&nbsp;Cuilian Sun,&nbsp;Yuhang Na,&nbsp;Haotian Sun,&nbsp;Jianhua Ma,&nbsp;Xueqin Wang,&nbsp;Xiaomin Cang","doi":"10.1111/jcmm.70352","DOIUrl":"10.1111/jcmm.70352","url":null,"abstract":"<p>Saturated fatty acid (SFA) accumulation in liver decreases hepatocyte lipophagy, a type of selective autophagy that degrades intracellular lipid droplets, leading to hepatic insulin resistance (IR), which contributes to simultaneous increases in liver glucose production and fat synthesis, resulting in hyperglycemia and dyslipidemia traits of type 2 diabetes mellitus (T2DM). Stromal cell derived factor-1 (SDF-1), a cytokine produced by hepatocytes, inhibits autophagy. In this study, we evaluated the hypothesis that SDF-1 promoted hepatic IR via inhibiting hepatocyte lipophagy during T2DM. Furthermore, we probed the downstream pathway participating in the role of SDF-1. The results showed that the neutralising of SDF-1 improved hepatic IR via promoting hepatocyte lipophagy in a mouse high-fat and high sucrose diet (HFHSD)-induced T2DM model. In vitro, SDF-1 expression and release increased in palmitic acid (PA, a kind of SFA)-treated hepatocytes. Meanwhile, SDF-1 bound to up-regulated C-X-C chemokine receptor type 4 (CXCR4) and C-X-C chemokine receptor type 7 (CXCR7) on PA-treated hepatocytes. Subsequently, SDF-1 inhibited lipophagy in PA-treated hepatocytes via CXCR4, rather than CXCR7. Finally, SDF-1/CXCR4/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway-inhibited lipophagy promotes PA-induced hepatocyte IR. Collectively, this study discovered that SDF-1 might inhibit lipophagy in SFA-treated hepatocytes to promote hepatic IR via CXCR4/AKT/mTOR pathway.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and Prognostic Accuracy of MiRNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis","authors":"Fatemeh Hasani,&nbsp;Mahdi Masrour,&nbsp;Sina Khamaki,&nbsp;Kimia Jazi,&nbsp;Saba Hosseini,&nbsp;Hadiseh Heidarpour,&nbsp;Mehrad Namazee","doi":"10.1111/jcmm.70337","DOIUrl":"10.1111/jcmm.70337","url":null,"abstract":"<p>Pancreatic cancer (PC) remains a significant contributor to global cancer mortality, with limited effective diagnostic and prognostic tools. MicroRNAs (miRNAs) have emerged as promising biomarkers for PC diagnosis and prognosis. A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus. Studies reporting sensitivity, specificity or area under the curve (AUC) for miRNAs in PC diagnosis, as well as hazard ratios (HRs) for survival evaluations, were included. Data extraction and quality assessment followed PRISMA guidelines. Meta-analyses were conducted using appropriate statistical methods. The protocol is registered in PROSPERO. Diagnostic analysis included 290 evaluations, revealing an overall AUC of 0.8226 for PC diagnosis. Subgroup analyses showed varying accuracies, with blood and tissue specimens yielding higher AUC values. Promising miRNAs with AUC values above 0.8 included miR-320, miR-1290, miR-93, miR-25, miR-451, miR-20, miR-21, miR-223 and miR-122. Prognostic analysis encompassed 46 studies, indicating significant associations between miRNA expression and overall survival (OS) and progression-free survival (PFS). The combined HR for studies reporting OS HRs higher than one was 1.7613 (95% CI: 1.5394–2.0152, <i>p</i> &lt; 0.0001; <i>I</i>² = 81.7%). Notable miRNAs with prognostic significance included miR-10, miR-21 and miR-221. Studies reporting OS HRs less than one had a pooled HR of 0.6805 (95% CI: 0.5862–0.7901, <i>p</i> &lt; 0.0001; <i>I</i>² = 65.4%). MiRNAs hold promise as diagnostic and prognostic biomarkers for PC. Blood and tissue specimens offer superior diagnostic accuracy, and several miRNAs show potential for predicting patient outcomes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification the Cellular Senescence Associated lncRNA LINC01579 in Gastric Cancer","authors":"Jiayong He,&nbsp;Ziyi Fu,&nbsp;Boya Zou,&nbsp;Xuetao Lei,&nbsp;Linhan Lei,&nbsp;Qingbin Yang,&nbsp;Guoxin Li","doi":"10.1111/jcmm.70360","DOIUrl":"10.1111/jcmm.70360","url":null,"abstract":"<p>Cellular senescence is a key promoter of tumorigenesis and malignant progression. This study aimed to develop a predictive model for assessing cellular senescence in gastric cancer (GC) outcomes. We identified senescence-related genes and lncRNAs from 375 stomach adenocarcinoma (STAD) patients and established a prognostic senescence score using multivariate Cox regression, validated in testing, TCGA-STAD and the combined TCGA-COAD and READ cohorts. The model's predictive efficacy was evaluated across clinical subgroups, tumour microenvironments and immune cell infiltration. A total of 116 senescence-related lncRNAs were filtered, and patients were clustered into two senescent subtypes. The lncRNA signature identified LINC01579 as an independent prognostic factor for GC. Low-risk groups showed prolonged overall survival, increased immune cell infiltration and reduced mutation load. Downregulation of LINC01579 using antisense oligonucleotides (ASOs) on normal human fibroblasts decreased cellular proliferation and migration in GC. Collectively, this study established and validated a promising prognostic model connecting senescence-related lncRNAs and clinical outcome in GC and provided potential senescence-related biomarkers for GC prognosis prediction.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Analysis of Bulk RNA Sequencing, eQTL, GWAS, and Single-Cell RNA Sequencing Reveals Key Genes in Hepatocellular Carcinoma","authors":"Mingkai Gong,&nbsp;Xian Zhao,&nbsp;Qingze Li,&nbsp;Qisheng Hao,&nbsp;Lichao Cha,&nbsp;Guofei Dong,&nbsp;Xinyu Li,&nbsp;Fabo Qiu,&nbsp;Dan Li,&nbsp;Lantian Tian","doi":"10.1111/jcmm.70359","DOIUrl":"10.1111/jcmm.70359","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) poses a continual therapeutic challenge owing to its elevated incidence and unfavourable prognosis, underscoring the critical need for the discovery of new molecular targets for detection and therapy. This work included the analysis of three publically accessible HCC datasets from TCGA and GEO. Instrumental variables (IVs) were derived via expression quantitative trait loci (eQTL) analysis, then followed by two-sample Mendelian randomisation (MR) analysis utilising publically available summary statistics. Key disease-associated genes were identified by assessing odds ratios and connecting them with differentially expressed genes across the datasets. The potential molecular mechanisms of these genes were clarified by functional enrichment analysis, clinical data analysis, single-cell RNA sequencing, GSEA, immune cell infiltration, and immune checkpoint analysis. These findings were then confirmed by Western blotting, immunohistochemistry, and quantitative PCR. By synthesising the outcomes from differential analysis of the databases, we found two genes, SERPING1 and STEAP3, that may be crucial in the beginning and development of HCC. These genes have a role in vital biological pathways and functions, such as metabolic regulation and macrophage activation. The significance of immunological-mediated processes in HCC was further highlighted by CIBERSORT analysis, which revealed a specific pattern of immune cell infiltration and the location of immunological checkpoints in the illness. The findings elucidate the molecular mechanisms of HCC and underscore critical genes implicated in its pathogenesis. SERPING1 and STEAP3 affect tumour cells and modify the tumour microenvironment (TME), indicating that targeting these genes may offer a viable immunotherapeutic approach for HCC in clinical settings.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metrnl and Cardiomyopathies: From Molecular Mechanisms to Therapeutic Insights","authors":"Miaomiao Xu,&nbsp;Xiaoguang Liu,&nbsp;Liming Lu,&nbsp;Zhaowei Li","doi":"10.1111/jcmm.70371","DOIUrl":"10.1111/jcmm.70371","url":null,"abstract":"<p>Cardiomyopathies, a diverse group of diseases affecting the heart muscle, continue to pose significant clinical challenges due to their complex aetiologies and limited treatment options targeting underlying genetic and molecular dysregulations. Emerging evidence indicates that Metrnl, a myokine, adipokine and cardiokine, plays a significant role in the pathogenesis of various cardiomyopathies. Therefore, the objective of this review is to examine the role and mechanism of Metrnl in various cardiomyopathies, with the expectation of providing new insights for the treatment of these diseases.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indole-3-Lactic Acid Inhibits Doxorubicin-Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway","authors":"Jiangfang Lian,&nbsp;Hui Lin,&nbsp;Zuoquan Zhong,&nbsp;Yongfei Song,&nbsp;Xian Shao,&nbsp;Jiedong Zhou,&nbsp;Lili Xu,&nbsp;Zhenzhu Sun,&nbsp;Yongyi Yang,&nbsp;Jufang Chi,&nbsp;Ping Wang,&nbsp;Liping Meng","doi":"10.1111/jcmm.70358","DOIUrl":"10.1111/jcmm.70358","url":null,"abstract":"<p>The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which is primarily attributed to its interaction with iron in mitochondria, leading to lipid peroxidation and myocardial ferroptosis. This study aimed to investigate the role of the gut microbiota-derived metabolite, indole-3-lactic acid (ILA), in mitigating DOX-induced cardiotoxicity (DIC). Cardiac function, pathological changes, and myocardial ferroptosis were assessed in vivo. The cardioprotective effects and mechanisms of ILA were explored using multi-omics approaches, including single-nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq, and were further validated in Nrf2 knockout mice. The findings revealed that DOX treatment disrupted gut microbiota, significantly reducing the levels of the tryptophan metabolite ILA. In DIC models, ILA supplementation markedly improved cardiac function, reduced collagen deposition, and mitigated cardiac atrophy. The bulk and snRNA-seq analyses indicated that myocardial ferroptosis played a crucial role in the cardioprotective effects of ILA. Experimental data demonstrated that ILA decreased DOX-induced ferroptosis in both DIC mice and DOX-treated H9C2 cells, evidenced by restoration of GPX4 and SLC7A11 levels and reduction of ACSL4. Mechanistically, ILA functions as a ligand for the aryl hydrocarbon receptor (AhR), leading to the upregulation of Nrf2 expression. The protective effects of ILA against ferroptosis were abolished by silencing AhR. Moreover, the beneficial effects of ILA on DIC were eliminated in Nrf2-deficient mice. In conclusion, ILA exerts therapeutic effects against DIC by inhibiting ferroptosis through activation of the AhR/Nrf2 signalling pathway. Identifying the cardioprotective role of the microbial metabolite ILA could offer viable therapeutic strategies for DIC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bayesian-optimized deep learning for identifying essential genes of mitophagy and fostering therapies to combat drug resistance in human cancers","authors":"Wenyi Jin,&nbsp;Junwen Chen,&nbsp;Zhongyi Li,&nbsp;Zhang Yubiao,&nbsp;Hao Peng","doi":"10.1111/jcmm.18254","DOIUrl":"10.1111/jcmm.18254","url":null,"abstract":"<p>Dysregulated mitophagy is essential for mitochondrial quality control within human cancers. However, identifying hub genes regulating mitophagy and developing mitophagy-based treatments to combat drug resistance remains challenging. Herein, BayeDEM (Bayesian-optimized Deep learning for identifying Essential genes of Mitophagy) was proposed for such a task. After Bayesian optimization, BayeDEM demonstrated its excellent performance in identifying critical genes regulating mitophagy of osteosarcoma (area under curve [AUC] of ROC: 98.96%; AUC of PR curve: 100%). CERS1 was identified as the most essential gene regulating mitophagy (mean (|SHAP value|): 4.14). Inhibition of CERS1 sensitized cisplatin-resistant osteosarcoma cells to cisplatin, restricting their growth, proliferation, invasion, migration and colony formation and inducing apoptosis. Mechanistically, inhibition of CERS1 restricted mitophagy to destroy the mitochondrial quality control in cisplatin-resistant osteosarcoma cells, including mitochondrial membrane potential loss and unfavourable mitochondrial dynamics, rendering them susceptible to cisplatin-induced apoptosis. More importantly, mitophagy facilitated the immunosuppressive microenvironment formation by significantly modulating T-cell differentiation, adhesion and antigen presentation, and mitophagy mainly affects malignant osteoblasts in the early-mid developmental stage. Immunologically, mitophagy potentially modulated the MIF signalling transmission between malignant osteoblasts and B cells, DCs, CD8+ T cells, NK cells and monocytes through the MIF-(CD74 + CXCR4) receptor–ligand interaction, thereby modulating the biological functions of these immune cells. Collectively, BayeDEM emerged as a promising tool for oncologists to identify pivotal genes governing mitophagy, thereby enabling mitophagy-centric therapeutic strategies to counteract drug resistance.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIT1 Promotes the Proliferation of Gliomas Through the Regulation of the PI3K/AKT/c-Myc Signalling Pathway","authors":"Zhen Liu,&nbsp;Hao-dong Jiang,&nbsp;Hao-yuan Kan,&nbsp;Li Zhang,&nbsp;Yu-xin Rao,&nbsp;Xiao-bing Jiang,&nbsp;Ming-hui Li,&nbsp;Qi Wang","doi":"10.1111/jcmm.70362","DOIUrl":"10.1111/jcmm.70362","url":null,"abstract":"<p>Recently, RIT1 has been implicated in a range of neurological disorders; however, its precise function in glioma pathogenesis is not yet well-defined. This study employed quantitative reverse transcription PCR (qRT-PCR), Western blotting (WB), immunohistochemistry (IHC) and additional methodologies to assess RIT1 expression levels in glioma tissues. Furthermore, the study investigated its influence on glioma progression through a series of functional experiments. Animal models were also utilised to elucidate the mechanistic role of RIT1, with a particular focus on its effects on the PI3K/AKT signalling pathway. Research findings showcased that RIT1 is significantly overexpressed in gliomas and exhibits a strong correlation with tumour grade and unfavourable clinical outcomes. Furthermore, RIT1 serves as an independent prognostic marker of poor prognosis. Functional assays demonstrate that RIT1 facilitates the aggressiveness of glioma cells by activating the PI3K/AKT signalling. Additionally, it promotes tumour proliferation by inhibiting apoptosis and accelerating cell cycle progression. This study demonstrates that RIT1 significantly contributes to the aggressive phenotype and unfavourable prognosis of glioma, indicating its ability as a therapeutic target for glioma treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 2","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}