Chae, Dong-Kyu Park, Jinyoung Cho, Moonsoo Ban, Eunmi Jang, Mihue Yoo, Young Sook Kim, Eunice EunKyeong Baik, Ja-Hyun Song, Eun Joo 2024-01-19T18:33:39Z 2024-01-19T18:33:39Z 2021-09-05 2019-12 1574-7891 https://pubs.kist.re.kr/handle/201004/119263 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. English WILEY MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-beta receptor I ubiquitination Article 10.1002/1878-0261.12581 1 MOLECULAR ONCOLOGY, v.13, no.12, pp.2663 - 2678 MOLECULAR ONCOLOGY 13 12 2663 2678 N scie scopus 000495179400001 2-s2.0-85074927661 Oncology Oncology Article DOWN-REGULATION BREAST-CANCER DEPENDENT DEGRADATION LIGASE SMURF2 GROWTH MICRORNA EXPRESSION METASTASIS INVASION PROLIFERATION lung cancer miR-195 miR-497 SMURF2 Transforming growth factor (TGF)-beta