title: miR-129 regulates cell proliferation by downregulating Cdk6 expression.
abstract: Reduced expression of miR-129 has been reported in multiple tumor cell lines and in primary tumors including medulloblastoma, undifferentiated gastric cancers, lung adenocarcinoma, endometrial cancer and colorectal carcinoma. There is also recent evidence of an anti-proliferative activity of miR-129 in tumor cell lines. Still, little is known about how miR-129 regulates cell proliferation. Here we found that lentiviral-mediated overexpression of miR-129 in mouse lung epithelial cells (E10 cells) results in significant G(1) phase arrest that eventually leads to cell death. miR-129 induce G(1) phase arrest in multiple human lung adenocarcinoma cell lines, suggesting miR-129 targeting of G(1)/S phase-specific regulators. Interestingly, we show that Cdk6, a kinase involved in G(1)-S transition, is a direct target of miR-129. We also found the downregulation of three other cell cycle-related novel targets of miR-129, including Erk1, Erk2 and protein kinase C epsilon (Prkce). We further show that among these targets, only Cdk6 is functionally relevant. Restoring expression of Cdk6, but not Prkce partially rescues the cell growth arrest and cell death phenotype that results from miR-129 overexpression. Together, our data indicate that miR-129 plays an important role in regulating cell proliferation by downregulation of Cdk6.
authors.affiliation: Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. jining@bu.edu
authors.forename: Junjie
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Letty
authors.initials: L
authors.lastname: Kwok
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: Peijun
authors.initials: P
authors.lastname: Liu
authors.forename: Catalina
authors.initials: C
authors.lastname: Perdomo
authors.forename: Darrell
authors.initials: D
authors.lastname: Kotton
authors.forename: Cyrus
authors.initials: C
authors.lastname: Vaziri
authors.forename: Christina
authors.initials: C
authors.lastname: Anderlind
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.forename: Wellington V
authors.initials: WV
authors.lastname: Cardoso
authors.forename: Jining
authors.initials: J
authors.lastname: Lü
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D016196:S Phase
chemical_list: D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D051744:Protein Kinase C-epsilon; D051361:Cyclin-Dependent Kinase 6; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3