MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-β receptor I ubiquitination

Dong Kyu Chae, Jinyoung Park, Moonsoo Cho, Eunmi Ban, Mihue Jang, Young Sook Yoo, Eunice Eun Kyeong Kim, Ja Hyun Baik, Eun Joo Song

Research output: Contribution to journalArticle

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-β (TGF-β) signaling through ubiquitin-mediated degradation of TGF-β 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 TβRI ubiquitination and cause the activation of the TGF-β 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-β signaling. Interestingly, miR-195 and miR-497 also reduced the invasion ability of lung cancer cells when cells were treated with TGF-β1. 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-β receptors through SMURF2, and suggest that miR-195 and miR-497 are potential therapeutic targets for lung cancer.

Original languageEnglish
Pages (from-to)2663-2678
Number of pages16
JournalMolecular Oncology
Volume13
Issue number12
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

Growth Factor Receptors
Ubiquitination
Transforming Growth Factors
Lung Neoplasms
Carcinogenesis
Aptitude
Ubiquitin-Protein Ligases
3' Untranslated Regions
Ubiquitin
Heterografts
Nude Mice
Neoplasms
Cell Survival
Up-Regulation
Databases
Messenger RNA
Growth

Keywords

  • lung cancer
  • miR-195
  • miR-497
  • SMURF2
  • Transforming growth factor (TGF)-β

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

Cite this

MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-β receptor I ubiquitination. / Chae, Dong Kyu; Park, Jinyoung; Cho, Moonsoo; Ban, Eunmi; Jang, Mihue; Yoo, Young Sook; Kim, Eunice Eun Kyeong; Baik, Ja Hyun; Song, Eun Joo.

In: Molecular Oncology, Vol. 13, No. 12, 01.12.2019, p. 2663-2678.

Research output: Contribution to journalArticle

Chae, Dong Kyu ; Park, Jinyoung ; Cho, Moonsoo ; Ban, Eunmi ; Jang, Mihue ; Yoo, Young Sook ; Kim, Eunice Eun Kyeong ; Baik, Ja Hyun ; Song, Eun Joo. / MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-β receptor I ubiquitination. In: Molecular Oncology. 2019 ; Vol. 13, No. 12. pp. 2663-2678.
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