title: MicroRNA-196a post-transcriptionally upregulates the UBE2C proto-oncogene and promotes cell proliferation in breast cancer.
abstract: Accumulating evidence has shown that miR-196a plays an important role in tumorigenesis and tumor progression in various types of cancer. miRNA profiling studies have suggested that miR-196a is highly overexpressed in breast cancer. However, the functional mechanism of miR-196a in breast cancer remains unclear. In the present study, we first showed that the expression of miR-196a was significantly upregulated in human breast cancer samples and breast cancer cell lines. Using a loss-of-function approach, we showed that the downregulation of miR-196a inhibited the proliferation of breast cancer cells in vitro and in vivo. Ubiquitin-conjugating enzyme E2C (UBE2C) gene as a cellular proto-oncogene, which was overexpressed and positively correlated with miR-196a expression in breast cancer tissues, was identified as a direct target of miR-196a. Moreover, in order to investigate whether miR-196a regulated cell growth in breast cancer cells by targeting UBE2C, rescue studies were performed in breast cancer cells. The restoration of UBE2C by transfecting UBE2C cDNA in anti-miR-196a-transfected breast cancer cells rescued the suppression of cell proliferation. In conclusion, the present study showed that miR-196a promoted cell proliferation by targeting UBE2C in breast cancer. Thus, miR-196a may be a potential oncogene in breast cancer and a promising therapeutic target in breast cancer treatment.
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Surgery Research Laboratory, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Surgery Research Laboratory, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Guanghuan
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D011499:Protein Processing, Post-Translational / Q000235:genetics; D000090063:Proto-Oncogene Mas; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C000715470:MAS1 protein, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes