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.
Bibliographical noteFunding Information:
We thank Dr. Kyung-Min Yang (Seoul National University) for help with the use of the pcDNA Flag-Smad2 and pcDNA-Flag-Smad4. This work was supported by a National Research Foundation of Korea (NRF), grant funded by the Korean government (MSIP) (20110021713 and 2015R1A2A2A04005596), the R&D Convergence Program of NST (National Research Council of Science & Technology) of Republic of Korea (CAP-16-03-KRIBB) and an intramural grant from the Korea Institute of Science and Technology (2E26990). The authors declare no conflict of interest.
© 2017 Wiley Periodicals, Inc.
Copyright 2017 Elsevier B.V., All rights reserved.
- lung cancer
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research