Unknown

Dataset Information

0

Epigenetic silencing of miR-200b is associated with cisplatin resistance in bladder cancer.


ABSTRACT: In this study, we identified microRNAs (miRNAs) involved in cisplatin (CDDP) resistance in bladder cancer (BCa). After establishing CDDP-resistant BCa cell lines (T24RC and EJ138RC), TaqMan arrays revealed that members of the miR-200 family (miR-200b, miR-200a and miR-429) were downregulated in T24RC as compared to parental T24 cells. miR-200b was associated with CDDP sensitivity in BCa cells, and its downregulation was associated with CpG island hypermethylation. Pharmacological demethylation using 5-aza-2'-deoxycytidine restored miR-200b expression, and the combination of 5-aza-2'-deoxycytidine + CDDP strongly inhibited T24RC cell proliferation. Microarray analysis revealed that miR-200b + CDDP induced genes involved in CDDP sensitivity or cytotoxicity, including IGFBP3, ICAM1 and TNFSF10, in the resistant cells. Expression and DNA methylation of miR-200b were inversely associated in primary BCa, and low expression/high methylation was associated with poor overall survival. These results suggest downregulation of miR-200b is associated with CDDP resistance in BCa. Epigenetic silencing of miR-200b may be a marker of CDDP resistance and a useful therapeutic target for overcoming CDDP resistance in BCa.

SUBMITTER: Shindo T 

PROVIDER: S-EPMC5966259 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

| GSE103250 | GEO
2013-01-01 | S-EPMC3633860 | BioStudies
2017-01-01 | S-EPMC5675767 | BioStudies
2010-01-01 | S-EPMC3004480 | BioStudies
2014-01-01 | S-EPMC4317938 | BioStudies
1000-01-01 | S-EPMC5347722 | BioStudies
2012-01-01 | S-EPMC3399424 | BioStudies
1000-01-01 | S-EPMC4741731 | BioStudies
2018-01-01 | S-EPMC5762681 | BioStudies
2020-01-01 | S-EPMC7434871 | BioStudies