The Multifunction Of miR-218-5p-Cx43 Axis In Breast Cancer

OncoTargets and Therapy

关键词: Cx43;    breast cancer;    miR-218-5p;    gemcitabine;    multifunction;   

DOI  :  

来源: DOAJ

【 摘 要 】

Chen Xia,1,* Hong Jiang,2,* Fugui Ye,3,* Zhigang Zhuang4 1Department of Medical Oncology, Hepatobiliary and Pancreatic Unit, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, People’s Republic of China; 2Medical Department, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, People’s Republic of China; 3Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 4Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen XiaDepartment of Medical Oncology, Hepatobiliary and Pancreatic Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, No.283 Tongzipo Road, Changsha 410013, People’s Republic of ChinaTel [phone]Email [e-mail] ZhuangDepartment of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 536 Chang-Le Road, Shanghai 200040, People’s Republic of ChinaTel [phone]Email [e-mail]: Gemcitabine is proven to be the first-line standard treatment of breast cancers. Yet, little is known involving gemcitabine resistance and remains largely to be elucidated.Materials and methods: We evaluated the expression of Cx43 in gemcitabine-resistant cells and parental cells by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses. Dual-luciferase reporter assay was applied to examine the epigenetic regulator of Cx43. The role of miR-218-5p-Cx43 axis on cell cytotoxicity, cell proliferation, colony formation, chemoresistance and migration was detected via mammalian expression vector and small short RNA (shRNA) transfection in vitro.Results: In this study, we found that Cx43 expression levels were significantly lower in gemcitabine-resistant cells than in the parental cells. On deep investigation of the epigenetic regulation of Cx43, a few miRNA candidates targeting Cx43 were derived. Through dual-luciferase reporter assay, Cx43 was proved to be a direct target of miR-218-5p. Besides, qPCR, Western blot demonstrated an inverse correlation between miR-218-5p and Cx43 expression in breast cancer cells, thus forming the miR-218-5p-Cx43 axis. Notably, miR-218-5p-Cx43 axis was found to be involved in the process of gemcitabine chemoresistance, cell proliferation and migration in breast cancer cells.Conclusion: Our findings suggested that miR-218-5p-Cx43 axis was versatile and indicated significant potency in breast cancer cells. More importantly, miR-218-5p-Cx43 axis might be valuable in translational medicine, with therapeutic and prognostic information.Keywords: Cx43, breast cancer, miR-218-5p, gemcitabine, multifunction

【 授权许可】

Unknown