MicroRNA-101-3p advances cisplatin sensitivity in bladder urothelial carcinoma through targeted silencing EZH2

Abstract

Objective : Chemotherapy is a major therapeutic method for bladder urothelial carcinoma (BUC), which can effectively improve the prognosis of BUC patients, but the chemoresistance often leads to chemotherapy failure. This study will research the regulatory roles and molecular mechanism of miR-101-3p in BUC chemoresistance. Materials and Methods : The quantitative real-time PCR was used to detect the expression of miRNA-101-3p and EZH2. The proliferation and chemoresistance were analyzed by CCK8 assay. Luciferase reporter assay was used to verify the combination between miR-101-3p and EZH2. Protein expression was detected by Western blotting. Flow cytometry was used to examine apoptosis rate. Results : The miR-101-3p expression was down-regulated in cisplatin (CDDP) resistant BUC cell line (T24/CDDP) and tissues, and was positively related to sensitivity of BUC to CDDP. In T24/CDDP cells, the up-regulation of miR-101-3p decreased the half maximal inhibitory concentration (IC50) to CDDP, depressed the expression of MRP1 protein, promote the CDDP-induced cytotoxicity, and advanced CDDP sensitivity. A series of in vitro experiments certified the EZH2 gene was a target gene of miR-101-3p, including luciferase reporter assay, western blotting and so on. Up-regulation of EZH2 largely reversed the regulatory effects of miR-101-3p enhancement on CDDP sensitivity in T24/CDDP cells. Conclusion : The expression of miR-101-3p is positively related to CDDP sensitivity of BUC, miR-101-3p advances sensitivity of BUC to CDDP through targeted silencing EZH2.

The Long Non-Coding RNA Prader Willi/Angelman Region RNA5 (PAR5) Is Downregulated in Anaplastic Thyroid Carcinomas Where It Acts as a Tumor Suppressor by Reducing EZH2 Activity

“…Additionally, circ-PRMT5 can upregulate EZH2 via sponging miR-377-382-498 in non-small cell lung cancer (NSCLC) [40]. Intriguingly, also many lncRNAs have been described to participate in the EZH2 oncogenic regulatory network [41,42], further highlighting the complex regulation of EZH2 activity in human cancer, and reinforcing its critical role in cancer progression.…”

Long non‐coding RNA SNHG6 promotes the growth and invasion of non‐small cell lung cancer by downregulating miR‐101‐3p

“…Some studies have demonstrated that miR‐101‐3p acts as a tumor suppressor in multiple cancers. It can inhibit cell growth and metastasis and facilitate chemotherapeutic sensitivity by targeting Pim‐1, TRIM44 or EZH2 . Moreover, miR‐101‐3p suppresses the growth and metastasis of NSCLC by inactivation of PI3K/AKT signaling .…”

<p>circ_0003418 Inhibits Tumorigenesis And Cisplatin Chemoresistance Through Wnt/β-Catenin Pathway In Hepatocellular Carcinoma</p>

“…Non-coding RNAs, including miRNAs, lncRNAs and circRNAs, play important roles in physiological and pathological processes such as proliferation, invasion, apoptosis and chemoresistance 6–8. CircRNAs are a new group of steady, endogenous and evolutionary conservative noncoding RNAs that are alien from linear RNA and are RNA molecules with 3ʹ and 5ʹ ends covalently linked in a circular structure 9.…”