MiR-550a-3-5p acts as a tumor suppressor and reverses BRAF inhibitor resistance through the direct targeting of YAP article

Min Ho Choe, Yina Yoon, Joon Kim, Sang Gu Hwang, Young Hoon Han, Jae Sung Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Although evidence has emerged to suggest that YAP overexpression is a crucial factor for tumor progression and resistance to targeted drugs in multiple cancers, the miRNA-mediated YAP regulation is still unclear. Here we show that the novel miR-550a-3-5p acts as a tumor suppressor and reverses BRAF inhibitor resistance through the direct targeting of YAP. Our data showed that the miR-550a-3-5p suppressed cell proliferation, metastasis, and tumor sphere formation through the direct inhibition of YAP and its oncogenic pathway in various cancer cell types. In addition, we showed that the YAP signature was associated with poor survival of colon cancer and identified an inverse correlation between miR-550a-3-5p and YAP in colon cancer tissues. Interestingly, this inverse correlation was regulated in a density-dependent manner. Furthermore, high levels of miR-550a-3-5p were associated with a good prognosis of esophageal cancer, which was suggestive of the clinical relevance of miR-550a-3-5p-mediated YAP regulation in multiple cancers. Importantly, we demonstrated that miR-550a-3-5p treatment sensitized vemurafenib-resistant colon and melanoma cells through YAP inhibition with reduced AKT activity. Moreover, the tumor-suppressive activity of miR-550a-3-5p and its sensitization effect for vemurafenib resistance were also observed in tumor xenograft models. Collectively, our data suggest that miR-550a-3-5p acts as a tumor suppressor through the targeting of oncogenic YAP and may be a new therapeutic tool for YAP-mediated BRAF inhibitor resistance in BRAF-mutant cancer cells.

Original languageEnglish
Article number698
JournalCell Death and Disease
Volume9
Issue number6
DOIs
Publication statusPublished - 2018 Jun 1

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Neoplasms
Colonic Neoplasms
Esophageal Neoplasms
MicroRNAs
Heterografts
Melanoma
Colon
Cell Proliferation
Neoplasm Metastasis
Pharmaceutical Preparations
PLX4032
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

MiR-550a-3-5p acts as a tumor suppressor and reverses BRAF inhibitor resistance through the direct targeting of YAP article. / Choe, Min Ho; Yoon, Yina; Kim, Joon; Hwang, Sang Gu; Han, Young Hoon; Kim, Jae Sung.

In: Cell Death and Disease, Vol. 9, No. 6, 698, 01.06.2018.

Research output: Contribution to journalArticle

Choe, Min Ho ; Yoon, Yina ; Kim, Joon ; Hwang, Sang Gu ; Han, Young Hoon ; Kim, Jae Sung. / MiR-550a-3-5p acts as a tumor suppressor and reverses BRAF inhibitor resistance through the direct targeting of YAP article. In: Cell Death and Disease. 2018 ; Vol. 9, No. 6.
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