title: MicroRNA-146a inhibits cell migration and invasion by targeting RhoA in breast cancer.
abstract: MicroRNAs (miRNAs) function as genetic modulators that regulate gene expression and are involved in a wide range of biological roles, including tumor cell migration and invasion. In the present study, we demonstrated that the migration and invasion activity in MDA-MB-231 breast cancer cells could be directly influenced by altering miR-146a expression. The expression of RhoA and miR-146a in the breast cancer cells showed an inverse correlation. Upregulation of miR-146a in the MDA-MB‑231 breast cancer cells by transfection of miR-146a mimics resulted in decreased RhoA protein levels. Conversely, downregulation of miR-146a by transfection of miR-146a inhibitor resulted in increased RhoA protein levels. To confirm the fact that RhoA is a potential target of miR-146a, luciferase reporter containing the RhoA 3' untranslated region (3'UTR) was constructed. The results demonstrated that the luciferase reporter activity was reduced after overexpression of miR-146a. Moreover, the luciferase reporter which was constructed with the RhoA 3'UTR mutant did not show significantly altered luciferase reporter activity. Furthermore, after treatment with the RhoA inhibitor exoenzyme C3 transferase protein, the migratory capacity of the MDA-MB-231 cells was not significantly altered even though the amount of miR-146a was changed. Our results indicate that miR-146a functions as a tumor suppressor in breast cancer cells. Downregulation of the expression of miR-146a increased the migration of MDA-MB-231 cells, due to the upregulation of RhoA expression.
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Organosilicon Chemistry and Material Technology of the Chinese Education Ministry, Hangzhou Normal University, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Xiongfa
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Fangqiong
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein