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MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-beta receptor I ubiquitination
- Title
- MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-beta receptor I ubiquitination
- Authors
- Chae, Dong-Kyu; Park, Jinyoung; Cho, Moonsoo; Ban, Eunmi; Jang, Mihue; Yoo, Young Sook; Kim, Eunice EunKyeong; Baik, Ja-Hyun; Song, Eun Joo
- Ewha Authors
- 송은주
- SCOPUS Author ID
- 송은주
- Issue Date
- 2019
- Journal Title
- MOLECULAR ONCOLOGY
- ISSN
- 1574-7891
1878-0261
- Citation
- MOLECULAR ONCOLOGY vol. 13, no. 12, pp. 2663 - 2678
- Keywords
- lung cancer; miR-195; miR-497; SMURF2; Transforming growth factor (TGF)-beta
- Publisher
- WILEY
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- SMURF2 is a member of the HECT family of E3 ubiquitin ligases that have important roles as a negative regulator of transforming growth factor-beta (TGF-beta) signaling through ubiquitin-mediated degradation of TGF-beta receptor I. However, the regulatory mechanism of SMURF2 is largely unknown. In this study, we identified that micro(mi)R-195 and miR-497 putatively target SMURF2 using several target prediction databases. Both miR-195 and miR-497 bind to the 3 '-UTR of the SMURF2 mRNA and inhibit SMURF2 expression. Furthermore, miR-195 and miR-497 regulate SMURF2-dependent T beta RI ubiquitination and cause the activation of the TGF-beta signaling pathway in lung cancer cells. Upregulation of miR-195 and miR-497 significantly reduced cell viability and colony formation through the activation of TGF-beta signaling. Interestingly, miR-195 and miR-497 also reduced the invasion ability of lung cancer cells when cells were treated with TGF-beta 1. Subsequent in vivo studies in xenograft nude mice model revealed that miR-195 and miR-497 repress tumor growth. These findings demonstrate that miR-195 and miR-497 act as a tumor suppressor by suppressing ubiquitination-mediated degradation of TGF-beta receptors through SMURF2, and suggest that miR-195 and miR-497 are potential therapeutic targets for lung cancer.
- DOI
- 10.1002/1878-0261.12581
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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