title: miR-185 suppresses tumor proliferation by directly targeting E2F6 and DNMT1 and indirectly upregulating BRCA1 in triple-negative breast cancer.
abstract: Breast cancer is a major public health problem all over the world, and the current treatment strategies are not potent enough for some patients, especially those with triple-negative breast cancer (TNBC). Recent studies have demonstrated that microRNAs (miRNA) play vital roles in the development of TNBC. In this study, we found that miR-185 was strongly downregulated in TNBC tissues and cell lines and that its expression levels were associated with lymph node metastasis, clinical stage, overall survival, and relapse-free survival in TNBC. We also found that ectopic expression of miR-185 inhibited TNBC cell proliferation in vitro and in vivo. We further identified that miR-185 directly targeted DNMT1 and E2F6, which resulted in a marked increase in the expression of BRCA1 at the mRNA and protein levels in TNBC. Our data suggest that miR-185 functions as a tumor suppressor in TNBC development. It is a promising prognostic biomarker and potential therapeutic target for TNBC.
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Cancer Prevention Center, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Minqing
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China. xiexm@sysucc.org.cn.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000235:genetics*; D015536:Down-Regulation; D050701:E2F6 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D050701:E2F6 Transcription Factor; C552431:MIRN185 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human