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

Cell Death & Disease
Min Ho ChoeJae-Sung Kim

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 acti...Continue Reading

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Citations

May 9, 2019·Future Oncology·Zhenxue TangGuohui Jiang
Apr 10, 2019·Journal of Translational Medicine·Yanyan Han
Jul 23, 2020·Frontiers in Oncology·Yuehui LiangFang Xiao
Sep 6, 2019·International Journal of Oncology·Hyun-Ju AnYoung-Hoon Han
Jul 2, 2020·International Journal of Molecular Sciences·Maria Letizia MottiMaria Vincenza Carriero
Jun 5, 2020·Journal of Experimental & Clinical Cancer Research : CR·Ming-Xin CaoYa-Ling Tang
Jul 17, 2019·Molecular Cancer Research : MCR·Zhaoji PanGuoping Niu
Feb 12, 2021·Pharmaceuticals·Eunsun JungTae-Su Han
Sep 18, 2021·Cancer Cell International·Liang WeiQinchuan Li

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Datasets Mentioned

BETA
GSE14333
GSE43732

Methods Mentioned

BETA
xenograft
transfection
nuclear translocation
PCR
X-ray
Assay

Software Mentioned

C6
TargetMiner
ImageJ
GSEA
Excel
XLSTAT
DIANA
CalcuSyn
PROGgene
Gene Set Enrichment Analysis ( GSEA

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