MIR-27a regulates the TGF-β signaling pathway by targeting SMAD2 and SMAD4 in lung cancer

Dong Kyu Chae, Eunmi Ban, Young Sook Yoo, Eunice Eun Kyeong Kim, Ja Hyun Baik, Eun Joo Song

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1992-1998
Number of pages7
JournalMolecular Carcinogenesis
Volume56
Issue number8
DOIs
Publication statusPublished - 2017 Aug

Bibliographical note

Funding 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.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • SMAD2
  • SMAD4
  • TGF-β
  • lung cancer
  • miR-27a

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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