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

doi:10.1002/mc.22655

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 journal › Article › peer-review

57 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 language	English
Pages (from-to)	1992-1998
Number of pages	7
Journal	Molecular Carcinogenesis
Volume	56
Issue number	8
DOIs	https://doi.org/10.1002/mc.22655
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/mc.22655

Cite this

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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.",

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author = "Chae, {Dong Kyu} and Eunmi Ban and Yoo, {Young Sook} and Kim, {Eunice Eun Kyeong} and Baik, {Ja Hyun} and Song, {Eun Joo}",

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: {\textcopyright} 2017 Wiley Periodicals, Inc. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

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AU - Kim, Eunice Eun Kyeong

AU - Baik, Ja Hyun

AU - Song, Eun Joo

N1 - 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.

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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