Repression of the miR-93-enhanced sensitivity of bladder carcinoma to chemotherapy involves the regulation of LASS2

Abstract

The aberrant expression of miRNA has an important function in bladder cancer (BC). Previous studies indicate that LASS2 is involved in the development of sensitivity to chemotherapy in cancer cells. In the present study, the miRNAs related to LASS2 were selected by using miRNA profiling to distinguish chemo-resistant and chemo-sensitive tumor specimens from patients. Higher levels of miR-93 were observed in the cisplatin-resistant BC cell line RT4, compared to the cell line T24. The role of miR-93 in chemo-sensitivity was demonstrated both in cell culture and mouse tumor xenograft models. We found that inhibiting miR-93 promoted cisplatin-induced apoptosis due to the accumulation of DNA damage. A reporter gene assay was performed, and the results showed miR-93 was not a target of the 3′ untranslated region of LASS2, but had an altered protein expression level. Inhibitors of miR-93 could also enhance the chemo-sensitivity of tumor cells transfected with si-LASS2, but the effect was very slight. These findings suggest that miR-93 plays an important role in the chemo-sensitivity of BC, and may be involved in regulating the LASS2 gene.