title: A methylation-based regulatory network for microRNA 320a in chemoresistant breast cancer.
abstract: We previously demonstrated that the overexpression of transient receptor potential channel C5 (TRPC5) and nuclear factor of activated T-cells isoform c3 (NFATC3) are essential for cancer chemoresistance, but how TRPC5 and NFATC3 are regulated was still unclear. In this study, microRNA 320a (miR-320a) was found to be down-regulated in chemoresistant cancer cells. MiR-320a directly targeted TRPC5 and NFATC3, and down-regulation of miR-320a triggered TRPC5 and NFATC3 overexpression. In chemoresistant cells, down-regulation of miR-320a was associated with regulation by methylation, which implicated promoter methylation of the miR-320a coding sequence. Furthermore, the transcription factor v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1), which inhibited miR-320a expression, was activated in chemoresistant cancer cells; such activation was associated with hypomethylation of the ETS-1 promoter. Lastly, the down-regulation of miR-320a and high expression of TRPC5, NFATC3, and ETS-1 were verified in clinically chemoresistant samples. Low expression of MiR-320a was also found to be a significant unfavorable predictor for clinic outcome. In conclusion, miR-320a is a mediator of chemoresistance by targeting TRPC5 and NFATC3. Expression of miR-320a is regulated by methylation of its promoter and that of ETS-1.
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology (D.X.H.), and Department of Cellular and Molecular Pharmacology, School of Medicine and Pharmaceutics (X.T.G., L.J., J.J., X.M.), Jiangnan University, Wuxi, People's Republic of China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: He
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology (D.X.H.), and Department of Cellular and Molecular Pharmacology, School of Medicine and Pharmaceutics (X.T.G., L.J., J.J., X.M.), Jiangnan University, Wuxi, People's Republic of China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Gu
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology (D.X.H.), and Department of Cellular and Molecular Pharmacology, School of Medicine and Pharmaceutics (X.T.G., L.J., J.J., X.M.), Jiangnan University, Wuxi, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology (D.X.H.), and Department of Cellular and Molecular Pharmacology, School of Medicine and Pharmaceutics (X.T.G., L.J., J.J., X.M.), Jiangnan University, Wuxi, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology (D.X.H.), and Department of Cellular and Molecular Pharmacology, School of Medicine and Pharmaceutics (X.T.G., L.J., J.J., X.M.), Jiangnan University, Wuxi, People's Republic of China maxin@jiangnan.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics*; D050778:NFATC Transcription Factors / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics; D050052:TRPC Cation Channels / Q000235:genetics
chemical_list: C494041:ETS1 protein, human; D035683:MicroRNAs; D050778:NFATC Transcription Factors; C494008:NFATC3 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human