Glucocorticoid receptor beta increases migration of human bladder cancer cells.

ABSTRACT: Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GR? expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GR? compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GR? in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3' untranslated region (UTR) of human GR? revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GR? by 3.8 fold. In addition, miR144 and GR? were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3'UTR of GR?. Sweet-P effectively prevented miR144 actions and decreased GR? expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GR? may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

SUBMITTER: McBeth L 

PROVIDER: S-EPMC5053652 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature