International Journal of Biological Sciences最新文献

{"title":"BAP31-ELAVL1-SPINK6 axis induces loss of cell polarity and promotes metastasis in hepatocellular carcinoma.","authors":"Xiyang Zhang, Jing Wang, Xiaohua Liang, Dongbo Jiang, Yuanjie Sun, Chenchen Hu, Feiming Hu, Yuanli He, Yubo Sun, Junqi Zhang, Jiaqi Ding, Sirui Cai, Yueyue Wang, Shuya Yang, Kun Yang","doi":"10.7150/ijbs.102566","DOIUrl":"10.7150/ijbs.102566","url":null,"abstract":"<p><p>Tumor metastasis is the main cause of hepatocellular carcinoma (HCC) related death. Loss of cell polarity may lead to weakened cell adhesion, epithelial-mesenchymal transition (EMT), and metastasis of HCC. However, the mechanism involved in HCC cells polarity loss is still less studied. Here, we found that BAP31 expression increased with tumor grade and metastasis. Moreover, BAP31 silencing inhibited invasion and migration and recovered the polarity of HCC cells. RNA-seq identified SPINK6 was a downstream gene of BAP31, and was associated with tumor stage and metastasis in HCC. IP-MS and IF assays showed that BAP31 bound to the RNA binding protein ELAVL1, and promoted its maturation. In addition, RIP, RNA-FISH, RNA stability and luciferase reporter assays confirmed that ELAVL1 could bind to the 3 'UTR region of SPINK6 mRNA to stabilize its expression. Depletion of SPINK6 inhibited the invasion and migration, re-established the cell polarity and suppressed EMT in HCC cells, while overexpression of SPINK6 partially counteracted BAP31/ELAVL1 knockdown caused attenuation of metastasis and recovery of polarity. Finally, <i>in vivo</i> experiments verified that BAP31-ELAVL1-SPINK6 axis induced cell polarity loss and promoted metastasis in HCC. Our study shed new light on the mechanism of cell polarity loss and metastasis in HCC.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1632-1648"},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483031","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":"Prolonged DEHP exposure enhances the stemness and metastatic potential of TNBC cells in an MSI2-dependent manner.","authors":"Mahendra Jadhao, Sheng-Kai Hsu, Dhanashri Deshmukh, Pei-Feng Liu, Shih-Feng Weng, Yih-Fung Chen, Chia-Yang Li, Chia-Yih Wang, Eing-Mei Tsai, Li-Fang Wang, Chien-Chih Chiu","doi":"10.7150/ijbs.101598","DOIUrl":"10.7150/ijbs.101598","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer, and human exposure to phthalates is a major health concern. DEHP, which is widely recognized as an endocrine disruptor, is associated with an increased risk of several diseases, including breast cancer. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and metastasis is the leading cause of TNBC-related mortality. However, the correlation between DEHP exposure and TNBC metastasis remains elusive. In the present study, we found that prolonged DEHP treatment enhanced the migration and invasion of TNBC cells both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, DEHP exposure induced Musashi RNA binding protein 2 (MSI2) overexpression, which subsequently activated the PI3K/Akt/NF-κB/MMP-9 axis to augment metastatic potential. MSI2 also promoted stemness. Interestingly, we identified a novel function of MSI2 in regulating the expression, distribution, and polarization of vimentin that is independent of its conventional RNA binding and translation regulation. Genetic knockdown of MSI2 potently abolished DEHP-mediated TNBC progression. Moreover, MSI2 depletion inhibited lung metastasis in metastatic mouse models but did not affect proliferation or tumor size. Intriguingly, miR-155-5p downregulation was observed after DEHP exposure, while mimic miR-155-5p treatment inhibited DEHP-induced TNBC migration, accompanied by reduced expression of MSI2 and vimentin. These findings suggested an inverse relationship between miR-155-5p levels and MSI2 expression. Taken together, MSI2 might serve as a potential therapeutic target and function as a prognostic biomarker for TNBC patients.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1705-1729"},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483096","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":"DARS2 Promotes Bladder Cancer Progression by Enhancing PINK1-Mediated Mitophagy.","authors":"Dongqing Li, Hang Su, Xiaolin Deng, Yuan Huang, Zihuan Wang, Jinge Zhang, Chen Chen, Zaosong Zheng, Qiong Wang, Shanchao Zhao, Zhe-Sheng Chen, Haiyong Chen, Lina Hou, Wanlong Tan, Fei Li","doi":"10.7150/ijbs.107632","DOIUrl":"10.7150/ijbs.107632","url":null,"abstract":"<p><p>Globally, bladder cancer is the tenth most common cancer. Mitophagy, a critical process regulating mitochondrial quantity and quality, has attracted increasing attention for its pivotal function in cancer. Nonetheless, its roles and underlying mechanisms in bladder cancer are yet to be elucidated. Therefore, in this study, 16 mitophagy-related genes were screened to construct a robust prognostic model with exceptional predictive accuracy for the outcomes of patients with bladder cancer. Of these genes, DARS2 was identified as a key regulator that significantly affected cancer progression. The findings established that DARS2 promoted the G1-to-S phase transition by upregulating CDK4 expression, thereby suppressing cellular senescence and driving cell proliferation. In addition, DARS2 augmented PINK1 expression, leading to increased PINK1-mediated mitophagy. Both <i>in vitro</i> and <i>in vivo</i> experiments confirmed that DARS2 inhibited cellular senescence and facilitated tumor progression by enhancing PINK1-mediated mitophagy. The observations from this study have provided novel insights into the multifaceted roles of DARS2-mediated mitophagy in bladder cancer. Targeting DARS2 and its regulation of mitophagy is a promising therapeutic strategy to improve the outcomes for patients with bladder cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1530-1544"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483025","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":"DNMT3a promotes LUAD cell proliferation and metastasis by activating the HDAC7 signalling pathway.","authors":"Menglong Jiang, Xin Zhou, Yingtong Feng, Peng Ding, Jinfeng Li, Di Lu, Jiapei Qin, Yibing Bai, An Wang, Chunfang Xia, Jinliang Wang, Xiaolong Yan, Zhiqiang Ma, Renquan Zhang","doi":"10.7150/ijbs.96509","DOIUrl":"10.7150/ijbs.96509","url":null,"abstract":"<p><p><b>Background:</b> Changes in DNA methylation patterns, in which DNA methyltransferases such as DNA methyltransferase 3 alpha (DNMT3a) play important roles, are closely related to the occurrence and development of tumours. However, the role and mechanism of DNMT3a in lung adenocarcinoma (LUAD) remain unknown. The aim of this study was to investigate the potential effect of DNMT3a on LUAD cell proliferation and metastasis and explore the underlying molecular mechanism. <b>Methods:</b> Immunohistochemistry and Kaplan‒Meier survival analysis were used to investigate the relationship between the expression of DNMT3a and histone deacetylase 7 (HDAC7) and the survival, prognosis and clinicopathological features of patients. The effects of DNMT3a on the proliferation and metastasis of LUAD cells were studied <i>in vivo</i> and <i>in vitro</i>. Recombinant lentivirus-mediated <i>in vitro</i> gene overexpression or knockdown, western blotting, Quantitative real-time polymerase chain reaction (qRT‒PCR) and other methods were used in this study to elucidate the potential molecular mechanisms by which DNMT3a promotes LUAD cell proliferation and metastasis. <b>Results:</b> High expression of DNMT3a or HDAC7 was positively correlated with poor prognosis, high AJCC 8th edition stage, and poor tumour differentiation in LUAD patients. LUAD patients with DNMT3a/HDAC7 co-low expression exhibited the worst prognosis. Upregulation of DNMT3a can promote LUAD cell proliferation and metastasis by upregulating HDAC7 and further activating the expression of downstream mediators ZEB1 and c-Myc. Conversely, overexpression of HDAC7 reversed the attenuation of tumour growth and metastasis and the suppression of c-Myc and ZEB1 expression mediated by downregulation of DNMT3a, further indicating the existence of positive feedback regulation between DNMT3a and HDAC7 in LUAD. <b>Conclusion:</b> Our findings first confirmed that DNMT3a acts as a tumour promoter inducing malignant progression of LUAD by upregulating HDAC7 and further inducing upregulation of ZEB1 and c-Myc. Targeting DNMT3a along with HDAC7 might be a promising therapeutic strategy for LUAD.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1585-1602"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483049","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":"High-dose Ascorbate Exhibits Anti-proliferative and Anti-invasive Effects Dependent on PTEN/AKT/mTOR Pathway in Endometrial Cancer <i>in vitro</i> and <i>in vivo</i>.","authors":"Xiaochang Shen, Jiandong Wang, Weimin Kong, Catherine John, Boer Deng, Shuning Chen, Haomeng Zhang, Jennifer Haag, Nikita Sinha, Wenchuan Sun, Angeles Alvarez Secord, Chunxiao Zhou, Victoria L Bae-Jump","doi":"10.7150/ijbs.102079","DOIUrl":"10.7150/ijbs.102079","url":null,"abstract":"<p><p>Endometrial cancer (EC) is the most common gynecological malignancy, frequently characterized by PTEN deletion, activation of the AKT/mTOR pathway, and limited effective treatment options for recurrent and advanced patients. High-dose ascorbate or combined with other chemotherapeutic agents shows potent antitumor effects <i>in vitro</i> and <i>in vivo</i>. In this study, high-dose ascorbate significantly inhibited cell proliferation and invasion, increased cellular stress and DNA damage, and induced cell cycle arrest and apoptosis in EC cells. Oral or intraperitoneal injections of high-dose ascorbate for 4 weeks effectively inhibited tumor growth in <i>LKB1^fl/flp53^fl/fl</i> -mouse model of EC, with intraperitoneal injections being more effective than oral administration. N-acetylcysteine partially reversed the antitumor effects of ascorbate in EC cells and tumor growth in <i>LKB1^fl/flp53^fl/fl</i> -mice. PTEN knockdown by shRNA reduced the antitumor sensitivity of EC cells to ascorbate, while inhibition of the AKT/mTOR pathway by Ipatasertib significantly enhanced the antitumor activity of ascorbate in EC cells. Ascorbate combined with paclitaxel synergistically inhibited tumor growth compared to either agent alone in <i>LKB1^fl/flp53^fl/fl</i> -mice. Overall, high-dose ascorbate exhibits antitumor activity partially through PTEN/AKT/mTOR and cell stress pathways, and these antitumor effects were heightened when combined with paclitaxel in EC. Clinical trials of ascorbate combined with paclitaxel deserve further investigation in EC patients.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1545-1565"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483105","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":"Inhibition of GRK2-PDE4D Axis Suppresses Fibroblast-Like Synoviocytes Hyperplasia and Alleviates Experimental Arthritis.","authors":"Dafei Han, Hanfei Sun, Renhao Zhang, Hui Ge, Paipai Guo, Rui Chu, Ruhong Fang, Yongsheng Han, Shufang He, Rui Li, Jiajie Tu, Wei Wei, Yang Ma, Qingtong Wang","doi":"10.7150/ijbs.100176","DOIUrl":"10.7150/ijbs.100176","url":null,"abstract":"<p><p>PDE4D has been reported to exhibit significantly elevated levels in the synovium of RA patients compared with OA, yet its role in RA remains underexplored. This study aimed to elucidate the role of the GRK2-PDE4D axis in FLSs and explore its potential as a therapeutic target for RA. Abundant expression of both PDE4D and GRK2 was observed in synovial tissues from both experimental arthritis animals and RA patients, with synchronized expression noted in RA patients. Global deletion of <i>Pde4d</i> reduced disease incidence and alleviated arthritis in CIA mice. TNF-α upregulated PDE4D expression, causing abnormal FLSs activation and hyperproliferation. Inhibiting PDE4D restored cAMP levels, thereby reducing FLSs hyperproliferation, migration, and anti-apoptosis. Mechanistically, TNF-α-induced PDE4D upregulation was dependent on GRK2. Inhibition of GRK2 with CP-25, an esterification modification of paeoniflorin, reduced PDE4D expression and FLSs proliferation, while restoring cAMP levels. Both genetic deficiency and pharmacological inhibition of GRK2 decreased PDE4D expression, ameliorating arthritis severity in animal models. This is the first study to investigate the role of PDE4D in RA and to clarify that it can be regulated by GRK2. These findings suggest that targeting the GRK2-PDE4D axis represents a promising therapeutic strategy for RA.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1513-1529"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483125","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":"Hexokinase 2 Suppression Alleviates the Catabolic Properties in Osteoarthritis via HMGA2 and Contributes to Pulsed Electromagnetic Field-mediated Cartilage Protection.","authors":"Chuncha Bao, Siyi Zhu, Dejiang Pang, Ming Yang, Jiapeng Huang, Fengsheng Wang, Yue Hou, Xiangxiu Wang, Yuan Feng, Haolun Yang, Junliang Jiang, Jing He, Chengqi He","doi":"10.7150/ijbs.101597","DOIUrl":"10.7150/ijbs.101597","url":null,"abstract":"<p><p>Abnormalities in glycolytic pathways are prominent factors in the pathogenesis of osteoarthritis (OA). The key glycolytic enzyme Hexokinase 2 (HK2) is highly expressed in chondrocytes in OA; however, its role remains unclear. Pulsed electromagnetic field (PEMF) is commonly used for the treatment of OA. However, the role of PEMF in cartilage damage and the underlying mechanisms are not well understood. Herein, we found that HK2 suppression down-regulated catabolic pathways and alleviated inflammatory responses in OA chondrocytes, whereas HK2 overexpression stimulated inflammation and catabolic levels; moreover, inhibition of HK2 has potential anti-inflammatory and anti-catabolic properties by regulating the expression of HMGA2. PEMF dramatically inhibited the increase in glycolytic activity and catabolic metabolism level in OA and could alleviate the OA phenotype by modulating the HK2/HMGA2 signaling axis. Suppressing HK2 via adeno-associated virus (AAV) in articular cartilage demonstrated that PEMF reduces cartilage damage and OA symptoms through HK2 knockdown. Furthermore, the HK2 inhibitor Lonidamine, in combination with PEMF, more effectively ameliorated cartilage degeneration in OA. Overall, our findings improve understanding of HK2's role in OA and offer new insights for targeting HK2 in treatment. Furthermore, our results provide new clues for the reducing of catabolism and cartilage damage using PEMF.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1459-1477"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483101","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":"Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.","authors":"Kiavash Hushmandi, Behzad Einollahi, E Hui Clarissa Lee, Reo Sakaizawa, Antonino Glaviano, Russel J Reiter, Seyed Hassan Saadat, Marzieh Ramezani Farani, Yun Suk Huh, Amir Reza Aref, Shokooh Salimimoghadam, Alan Prem Kumar","doi":"10.7150/ijbs.96155","DOIUrl":"10.7150/ijbs.96155","url":null,"abstract":"<p><p>Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, including urological cancers. However, a series of challenges, including tumor heterogeneity, TME, Ab immunogenicity, adverse effects, serum half-life, low response rates, and drug resistance, hamper the application of BsAbs. In this review, we provide insights into the most common BsAb platforms with different mechanisms of action, which are under preclinical and clinical research, along with ways to overcome the challenges in BsAb administration for treating urological cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1410-1435"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483001","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":"Chloroquine Suppresses Colorectal Cancer Progression via Targeting CHKA and PFKM to inhibit the PI3K/AKT Pathway and the Warburg Effect.","authors":"Yanqing Liu, Yongping Zhu, Liwei Gu, Kexin Li, Ang Ma, Li Liu, Yuqing Meng, Junzhe Zhang, Shengnan Shen, Qiaoli Shi, Dandan Liu, Xinwei Zhang, Shujie Zhang, Xin Chai, Peng Gao, Jiale Xing, Yaxu Wang, Honglin Chen, Rui Liu, Qingfeng Du, Haitao Liu, Lingyun Dai, Jigang Wang","doi":"10.7150/ijbs.101921","DOIUrl":"10.7150/ijbs.101921","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide and has become a recognized global health problem. Therefore, the search for new anti-CRC agents or the exploration of new effective drug targets for CRC therapy is urgent. Chloroquine (CQ) is a widely-used antimalarial drug and has shown anti-proliferative effects in CRC. However, the underlying mechanisms are not well understood, particularly as the direct targets of CQ have not been identified. In this study, choline kinase alpha (CHKA) and ATP-dependent 6-phosphofructokinase, muscle type (PFKM) were identified and verified as the binding targets of CQ. CQ specifically binds to CHKA, inhibits its expression and enzymatic activity, and downregulates the downstream phosphorylation of PI3K and AKT, thereby suppressing tumor cell proliferation and inducing apoptosis. CQ also binds to PFKM and inhibits its expression and activity, thereby blocking the Warburg effect. In addition, the downregulation of CHKA can decrease the expression of PFKM and inhibit its activity, thereby blocking the Warburg effect. These observations shed new light on the antitumor mechanisms of CQ and provide new evidence for the close relationship between the PI3K/AKT signaling pathway and the Warburg effect, providing new therapeutic targets for treating CRC.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1619-1631"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483018","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":"Mannose Inhibits NSCLC Growth and Inflammatory Microenvironment by Regulating Gut Microbiota and Targeting OGT/hnRNP R/JUN/IL-8 Axis.","authors":"Haoyi Jin, Huanghe He, Jijia Li, Xi Liu, Qi Cai, Jiang Shi, Zhexue Hao, Jianxing He","doi":"10.7150/ijbs.107256","DOIUrl":"10.7150/ijbs.107256","url":null,"abstract":"<p><p>Recent studies have reported direct antitumor effects of mannose, a natural six-carbon monosaccharide, in the treatment of cancer. Herein, we utilized cancer cell lines, animal models, organoids and experimental techniques such as multi-omics and cellular experiments to investigate the regulatory effects of mannose on NSCLC growth and the inflammatory microenvironment. We demonstrated that mannose can inhibit cancer cell growth, inflammatory cell infiltration and inflammatory cytokine expression in NSCLC tissue, and enhance the antitumor efficacy of immune checkpoint inhibitor both <i>in vitro</i> and <i>in vivo</i>. Orally administered mannose increased the proportion of probiotics in the gut microbiota, the abundance of anti-inflammatory and antitumor metabolites in the blood and feces of NSCLC-bearing mice. In NSCLC cells, mannose reduced JUN mRNA stability and subsequent IL-8 transcription of NSCLC cells by directly targeting OGT to suppress the O-GlcNAc glycosylation of hnRNP R, which bound and stabilized JUN mRNA in an O-GlcNAc glycosylation dependent manner. Taken together, our study demonstrated that mannose can suppress NSCLC by inhibiting tumor growth and the inflammatory microenvironment, and serve as a promising adjunct medication.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1566-1584"},"PeriodicalIF":8.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483128","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}