Journal
MOLECULAR CARCINOGENESIS
Volume 56, Issue 8, Pages 1992-1998Publisher
WILEY
DOI: 10.1002/mc.22655
Keywords
lung cancer; miR-27a; SMAD2; SMAD4; TGF-
Categories
Funding
- Korean government (MSIP) [20110021713, 2015R1A2A2A04005596]
- R&D Convergence Program of NST of Republic of Korea [CAP-16-03-KRIBB]
- KIST [2E26990]
- Ministry of Science & ICT (MSIT), Republic of Korea [2E26990] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The transforming growth factor- (TGF-) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF- 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--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.
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