Knockdown of microRNA-130b improves doxorubicin sensitivity in bladder urothelial carcinoma by negatively regulating cylindromatosis expression

Abstract

Introduction: Chemotherapeutic resistance reduces the sensitivity of bladder urothelial carcinoma (BUC) to chemotherapeutic drugs and contributes a barrier leading to treatment failure. The purpose of this research project is to investigate the regulatory effects of miR-130b on chemotherapeutic drug resistance of BUC and its mechanism. Material and methods: The relative expression of miRNA-130b and cylindromatosis (CYLD) was examined using real-time quantitative PCR. The cell proliferation and doxorubicin sensitivity were detected with the enhanced CCK-8 assay. The specific combination of miR-130b and CYLD was verified with the luciferase reporter gene assay. Protein expression was detected by Western blot. Results: Our study found that miR-130b was up-regulated in doxorubicin-insensitive BUC tissues and cell lines, and its high expression was negatively related to doxorubicin sensitivity in BUC. The miR-130b knockdown reduced the IC 50 of doxorubicin and improved doxorubicin sensitivity of J82/Dox and T24/Dox cells. For the regulation mechanism analysis of miR-130b, bioinformatics analysis software was used to predict the potential targets of miR-130b, including the CYLD gene. The following luciferase activities assay, quantitative real time-PCR and western blot identified the CYLD gene as a target of miR-130b. Knockdown of CYLD reversed miR-130b's regulatory roles in doxorubicin sensitivity in J82/Dox and T24/Dox cells. Conclusions: High expression of miR-130b is negatively related to doxorubicin sensitivity in BUC, and knockdown of miR-130b improves doxorubicin sensitivity in BUC by negatively regulating CYLD expression. Our findings will provide guidance for the clinical chemotherapy of BUC.

A CircRNA–miRNA–mRNA Network for Exploring Doxorubicin- and Myocet-Induced Cardiotoxicity in a Translational Porcine Model

“…The increased expression of miR-130b was negatively related to DOX sensitivity in patients with bladder carcinoma. [33] Furthermore, we observed that differences in circRNA expression were only evident at specific doses (Figure 2A,B). Both Figures 2A and 2B clearly show a significant difference between MYO-treated and control cells.…”

The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment

“…Though this review focuses on miRNAs, there are other non-coding RNAs, such as long non-coding RNAs and circular RNAs, that have similarly been implicated in BCa resistance and recurrence and which should be explored further, especially since these networks also involved miRNAs [ 51 , 130 , 131 , 132 ]. This includes Cdr1as, a circular RNA that mediates bladder cancer chemotherapeutic response via miR-1270 [ 132 ] and circ-BPTF, which promotes recurrence through interaction with miR-31-5p [ 133 ].…”