MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-beta receptor I ubiquitination
- 주제(키워드) lung cancer , miR-195 , miR-497 , SMURF2 , Transforming growth factor (TGF)-beta
- 주제(기타) Oncology
- 설명문(일반) [Chae, Dong-Kyu; Park, Jinyoung; Cho, Moonsoo; Ban, Eunmi; Yoo, Young Sook] Korea Inst Sci & Technol, Mol Recognit Res Ctr, Seoul, South Korea; [Chae, Dong-Kyu; Baik, Ja-Hyun] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea; [Cho, Moonsoo] Korea Univ Sci & Technol, KIST Sch, Div Biomed Sci & Technol, Seoul, South Korea; [Jang, Mihue; Kim, Eunice EunKyeong] Korea Inst Sci & Technol, Biomed Res Inst, Seoul, South Korea; [Song, Eun Joo] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Song, Eun Joo] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 WILEY
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000172040
- 본문언어 영어
- Published As https://dx.doi.org/10.1002/1878-0261.12581
- PubMed https://pubmed.ncbi.nlm.nih.gov/31581360
초록/요약
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.
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