title: miR-200c inhibits breast cancer proliferation by targeting KRAS.
abstract: The microRNA, miR-200c, is involved in the tumorigenesis and progression of a variety of cancers. The purpose of this study was to investigate the expression, mechanism and prognostic roles of miR-200c in breast cancer. We found that miR-200c was downregulated in both breast cancer tissue and cell lines using quantitative real-time PCR (qRT-PCR). In situ hybridization (ISH) and microarrays showed that low miR-200c expression was associated with poor patient overall survival (OS) and disease free survival (DFS). We used luciferase reporter plasmids to find that miR-200c inhibited the AKT and ERK pathways by directly targeting KRAS. Repression of KRAS by miR-200c suppressed the proliferation and survival of breast cancer cells in vitro and in vivo. miR-200c also had an anti-tumor effect by negatively regulating KRAS in a xenograft mouse model. Our findings provide clues regarding the role of miR-200c as a tumor suppressor in breast cancer through the inhibition of KRAS translation both in vitro and in vivo. miR-200c could be a potential therapeutic target in breast cancer.
authors.affiliation: Department of Breast Oncology, 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: Cailu
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Ultrasond, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Long-Zhong
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: Department of Ultrasond, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Pei
authors.affiliation: Department of Breast Oncology, 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, 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, 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 Breast Oncology, 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: School of Chinese Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Breast Oncology, 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, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C117307:KRAS protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; breast cancer; miR-200c; microRNA; proliferation