title: MiR-335 inhibits migration of breast cancer cells through targeting oncoprotein c-Met.
abstract: Metastasis is the leading cause of death in patients with breast cancer and aberrantly expressed microRNAs (miRNAs) are highly associated with this process. A previous study has shown that miR-335 is downregulated in breast cancer and can suppress tumor invasion and metastasis. Emerging evidences indicate that c-Met is implicated in cell scattering, migration, and invasion. However, little is known about the relationship between miR-335 expression and c-Met alteration in breast cancer. In the present study, we found that miR-335 expression was downregulated and c-Met protein expression was upregulated in two human breast cell lines. MiR-335 was found to negatively regulate c-Met protein level by directly targeting its 3' untranslated region (UTR). Forced expression of miR-335 decreased c-Met expression at protein levels and consequently diminished hepatocyte growth factor (HGF)-induced phosphorylation of c-Met and subsequently inhibited HGF promotion of breast cancer cell migration in a c-Met-dependent manner. MiR-335 expression was increased after 5-aza-2'-deoxycytidine (5-AZA-CdR) treatment, and 5-AZA-CdR treatment resulted in the same phenotype as the effect of miR-335 overexpression. Taken together, these results demonstrate that miR-335 suppresses breast cancer cell migration by negatively regulating the HGF/c-Met pathway.
authors.affiliation: Molecular Medicine & Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.forename: Fan
authors.initials: F
authors.lastname: Zeng
authors.forename: Jia-Yan
authors.initials: JY
authors.lastname: Wu
authors.forename: Hai-Yu
authors.initials: HY
authors.lastname: Li
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Fan
authors.forename: Li
authors.initials: L
authors.lastname: Mai
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Ma
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Fang-zhou
authors.initials: FZ
authors.lastname: Song
mesh_terms: D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000235:genetics; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C556347:MIRN335 microRNA, human; D035683:MicroRNAs; D017228:Hepatocyte Growth Factor; D000077209:Decitabine; D019859:Proto-Oncogene Proteins c-met; D001374:Azacitidine