title: miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition of the cell cycle and the epithelial to mesenchymal transition in cervical cancer cells.
abstract: MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate target gene expression, play an important role in cancer initiation, progression, and metastasis. However, the role of many miRNAs in cervical cancer is not fully understood. In this study, we found that miR-212 and miR-132 from the same gene cluster are downregulated in human cervical cancer tissues when compared with adjacent noncancerous tissues. The overexpression of miR-212/132 not only led to a delay in the G1/S phase transition and repressed cell proliferation but also resulted in an increase in E-cadherin expression and a decrease in vimentin, suppressing the epithelial to mesenchymal transition and migration and invasion in cervical cancer cells. Subsequently, SMAD2 was identified as a common target of miR-212/132 and was found to be negatively regulated by miR-212/132 at the mRNA and protein levels. Furthermore, SMAD2 silencing led to the same effect on cervical cancer cells as miR-212/132 overexpression. Importantly, SMAD2 overexpression partially reversed the cellular phenotypes induced by miR-212/132 overexpression. In conclusion, our study indicated that miR-212/132 functions as tumor suppressor by targeting SMAD2 in cervical cancer.
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Zhao
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of pathogenic biology, Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D015536:Down-Regulation / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D016196:S Phase; D051899:Smad2 Protein / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C547077:MIRN132 microRNA, human; C551411:MIRN212 microRNA, human; D035683:MicroRNAs; C497782:SMAD2 protein, human; D051899:Smad2 Protein
keywords: EMT; SMAD2; cervical cancer; miR-212/132; miRNA