title: MIR-27a regulates the TGF-β signaling pathway by targeting SMAD2 and SMAD4 in lung cancer.
abstract: The transforming growth factor-β (TGF-β) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF-β signaling. The aberrant expression of these genes is implicated in some cancers. However, the mechanisms of SMAD2 and SMAD4 dysregulation are poorly understood. In this study, we observed that miR-27a was upregulated in lung cancer cell lines and patients. In addition, SMAD2 and SMAD4 genes were identified as targets of miR-27a by several target prediction databases and experimental validation. Functional studies revealed that miR-27a overexpression decreased SMAD2 and SMAD4 mRNA and protein levels. Furthermore, miR-27a contributed to cell proliferation and invasion by inhibiting TGF-β-induced cell cycle arrest. These results suggest that miR-27a may function as an oncogene by regulating SMAD2 and SMAD4 in lung cancer. Thus, miR-27a may be a potential target for cancer therapy.
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, South Korea.|School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Chae
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, South Korea.
authors.forename: Eunmi
authors.initials: E
authors.lastname: Ban
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, South Korea.
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Yoo
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, South Korea.
authors.forename: Eunice EunKyeong
authors.initials: EE
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, South Korea.
authors.forename: Eun Joo
authors.identifier: 0000-0002-2420-6666
authors.initials: EJ
authors.lastname: Song
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics*; D051901:Smad4 Protein / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta
keywords: SMAD2; SMAD4; TGF-β; lung cancer; miR-27a