title: 17β-estradiol up-regulates miR-155 expression and reduces TP53INP1 expression in MCF-7 breast cancer cells.
abstract: In estrogen responsive breast cancer cells, estradiol (E2) is a key regulator of cell proliferation and survival. MiR-155 has emerged as an "oncomiR", which is the most significantly up-regulated miRNA in breast cancer. Moreover, miR-155 is higher in ERα (+) breast tumors than ERα (-), but no one has examined whether E2 regulates miR-155 expression in MCF-7 cells. In this study, the aim was to explore whether miR-155 involved in E2 regulated expression of estrogen responsive genes. We evaluated miR-155 expression in human breast cancer cells by real-time PCR, finding out miR-155 was overexpressed in MCF-7 cells compared with MDA-MB-231 cells. Treatment with E2 in MCF-7 cells increased miR-155 expression, promoting proliferation and decreasing apoptosis, similarly, transfection of miR-155m to MCF-7 cells gave the similar results. In contrast, inhibited miR-155 expression by transfection with miR-155 inhibitors reduced proliferation and promoted apoptosis of MCF-7 cells. Moreover, TP53INP1 is one of the targets of miR-155. E2 negatively regulated TP53INP1 mRNA expression and the protein expression of TP53INP1, cleaved-caspase-3, -8, -9, and p21, whereas transfection with miR-155 inhibitors increased TP53INP1, cleaved-caspase-3, -8, -9, and p21 protein level. These results demonstrated that E2 promoted breast cancer development and progression possibly through increasing the expression of miR-155, which was overexpressed in MCF-7 cells, contributes to proliferation of MCF-7 cells possibly through down-regulating TP53INP1.
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Huayu
authors.initials: H
authors.lastname: Deng
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006360:Heat-Shock Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C429767:TP53INP1 protein, human; D004958:Estradiol; D020169:Caspases