{"title":"乳腺癌中ARHGAP40的高甲基化缺失及其临床意义","authors":"Yumei Tao, Jingyu Wang, Xiaoyan Ren, Lili Gu, Jingjun Sun, Jiandong Wang","doi":"10.2174/0115665240370635250617210156","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). The expression and biological roles of ARHGAP40 in breast cancer are unknown. We aimed to investigate the expression of ARHGAP40 and its epigenetic mechanism in breast cancer.</p><p><strong>Methods: </strong>The expression level of ARHGAP40 was examined in breast cancer cell lines and tissues. The methylation status of ARHGAP40 was analyzed using a bisulfite sequencing PCR (BSP). The biological roles of ARHGAP40 in breast cancer were investigated.</p><p><strong>Results: </strong>ARHGAP40 mRNA was significantly expressed in MCF-7 and weakly in MDA-MB-231, whereas methylated ARHGAP40 was detected in MDA-MB-231 and partly in MCF-7. ARHGAP40 protein was positively expressed in normal breast epithelial cells in all paracancerous tissues. The expression level of ARHGAP40 was significantly associated with age, TNM stage, lymph node metastasis, molecular subtypes, proliferative marker Ki67, and HER2 expression. The overall survival (OS) of patients with high expression of ARHGAP40 was longer than those with low expression. Overexpression of ARHGAP40 in MCF-7 and MDA-MB-231 cells induced apoptosis and suppressed cell proliferation. The opposite outcomes were observed in the ARHGAP40 knockdown experiment.</p><p><strong>Conclusion: </strong>Our data suggested ARHGAP40 to be downregulated in breast cancer due to hypermethylation. ARHGAP40 was found to act as a tumor suppressor in breast cancer and could be a potential therapeutic target for breast cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Loss of ARHGAP40 in Breast Cancer by Hypermethylation and its Clinical Significance.\",\"authors\":\"Yumei Tao, Jingyu Wang, Xiaoyan Ren, Lili Gu, Jingjun Sun, Jiandong Wang\",\"doi\":\"10.2174/0115665240370635250617210156\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). The expression and biological roles of ARHGAP40 in breast cancer are unknown. We aimed to investigate the expression of ARHGAP40 and its epigenetic mechanism in breast cancer.</p><p><strong>Methods: </strong>The expression level of ARHGAP40 was examined in breast cancer cell lines and tissues. The methylation status of ARHGAP40 was analyzed using a bisulfite sequencing PCR (BSP). The biological roles of ARHGAP40 in breast cancer were investigated.</p><p><strong>Results: </strong>ARHGAP40 mRNA was significantly expressed in MCF-7 and weakly in MDA-MB-231, whereas methylated ARHGAP40 was detected in MDA-MB-231 and partly in MCF-7. ARHGAP40 protein was positively expressed in normal breast epithelial cells in all paracancerous tissues. The expression level of ARHGAP40 was significantly associated with age, TNM stage, lymph node metastasis, molecular subtypes, proliferative marker Ki67, and HER2 expression. The overall survival (OS) of patients with high expression of ARHGAP40 was longer than those with low expression. Overexpression of ARHGAP40 in MCF-7 and MDA-MB-231 cells induced apoptosis and suppressed cell proliferation. The opposite outcomes were observed in the ARHGAP40 knockdown experiment.</p><p><strong>Conclusion: </strong>Our data suggested ARHGAP40 to be downregulated in breast cancer due to hypermethylation. ARHGAP40 was found to act as a tumor suppressor in breast cancer and could be a potential therapeutic target for breast cancer.</p>\",\"PeriodicalId\":10873,\"journal\":{\"name\":\"Current molecular medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current molecular medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115665240370635250617210156\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115665240370635250617210156","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Loss of ARHGAP40 in Breast Cancer by Hypermethylation and its Clinical Significance.
Objective: ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). The expression and biological roles of ARHGAP40 in breast cancer are unknown. We aimed to investigate the expression of ARHGAP40 and its epigenetic mechanism in breast cancer.
Methods: The expression level of ARHGAP40 was examined in breast cancer cell lines and tissues. The methylation status of ARHGAP40 was analyzed using a bisulfite sequencing PCR (BSP). The biological roles of ARHGAP40 in breast cancer were investigated.
Results: ARHGAP40 mRNA was significantly expressed in MCF-7 and weakly in MDA-MB-231, whereas methylated ARHGAP40 was detected in MDA-MB-231 and partly in MCF-7. ARHGAP40 protein was positively expressed in normal breast epithelial cells in all paracancerous tissues. The expression level of ARHGAP40 was significantly associated with age, TNM stage, lymph node metastasis, molecular subtypes, proliferative marker Ki67, and HER2 expression. The overall survival (OS) of patients with high expression of ARHGAP40 was longer than those with low expression. Overexpression of ARHGAP40 in MCF-7 and MDA-MB-231 cells induced apoptosis and suppressed cell proliferation. The opposite outcomes were observed in the ARHGAP40 knockdown experiment.
Conclusion: Our data suggested ARHGAP40 to be downregulated in breast cancer due to hypermethylation. ARHGAP40 was found to act as a tumor suppressor in breast cancer and could be a potential therapeutic target for breast cancer.
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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