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

Pub. Date : 2020 Jun 10

PMID : 32522234






5 Functional Relationships(s)
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1 HIF-1alpha-dependent miR-424 induction confers cisplatin resistance on bladder cancer cells through down-regulation of pro-apoptotic UNC5B and SIRT4. Cisplatin unc-5 netrin receptor B Homo sapiens
2 CDDP-mediated suppression of xenograft bladder tumor growth was prohibited by the addition of miR-424, whereas ectopic expression of UNC5B or SIRT4 partially restored miR-424-dependent decrease in CDDP sensitivity of bladder cancer 5637 and T24 cells. Cisplatin unc-5 netrin receptor B Homo sapiens
3 Moreover, knockdown of UNC5B or SIRT4 prohibited CDDP-mediated proteolytic cleavage of PARP and also decreased CDDP sensitivity of these cells. Cisplatin unc-5 netrin receptor B Homo sapiens
4 Moreover, knockdown of UNC5B or SIRT4 prohibited CDDP-mediated proteolytic cleavage of PARP and also decreased CDDP sensitivity of these cells. Cisplatin unc-5 netrin receptor B Homo sapiens
5 CONCLUSIONS: Collectively, our current results strongly suggest that miR-424 tightly participates in the acquisition/maintenance of CDDP-resistant phenotype of bladder cancer cells through down-regulation of its targets UNC5B and SIRT4, and thus combination chemotherapy of CDDP plus HIF-1alpha/miR-424 inhibition might have a significant impact on hypoxic as well as normoxic bladder cancer cells. Cisplatin unc-5 netrin receptor B Homo sapiens