HIF-1α-dependent miR-424 induction confers cisplatin resistance on bladder cancer cells through down-regulation of pro-apoptotic UNC5B and SIRT4.

Journal of Experimental & Clinical Cancer Research : CR
Meng YuYuyan Zhu

Abstract

Chemo-resistance of bladder cancer has been considered to be one of the serious issues to be solved. In this study, we revealed pivotal role of miR-424 in the regulation of CDDP sensitivity of bladder cancer cells. The cytotoxicity of cisplatin and effect of miR-424 were assessed by flow cytometry and TUNEL. Transcriptional regulation of miR-424 by HIF-1α was assessed by Chromatin immunoprecipitation (ChIP). Effect of miR-424 on expression of UNC5B, SIRT4 (Sirtuin4) and apoptotic markers was measured by QRT-PCR and/or Western blot. The regulation of miR-424 for UNC5B and SIRT4 were tested by luciferase reporter assay. The 5637-inoculated nude mice xenograft model was used for the in vivo study. The clinical significance of miR-424 was demonstrated mainly through data mining and statistical analysis of TCGA. In this study, we have found for the first time that cisplatin (CDDP) induces the expression of miR-424 in a HIF-1α-dependent manner under normoxia, and miR-424 plays a vital role in the regulation of CDDP resistance of bladder cancer cells in vitro. Mechanistically, we have found that UNC5B and SIRT4 are the direct downstream target genes of miR-424. CDDP-mediated suppression of xenograft bladder tumor growth was prohibited...Continue Reading

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Citations

Feb 16, 2021·Frontiers in Oncology·Yibing BaiYanqiao Zhang
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sepideh MirzaeiKwang-Seok Ahn
Jun 17, 2021·Neoplasia : an International Journal for Oncology Research·Myung-Chul KimYongbaek Kim

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Methods Mentioned

BETA
transfection
xenograft
PCR
RNA-seq
FACS
immunoprecipitation
ChIP

Software Mentioned

ImageJ
miRanda
TargetScan
- win64

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