1. Department of Anatomy, College of Basic Medicine, China Medical University, Shenyang, 110001, China
2. Department of Urinary surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, China
3. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China
Objective: To investigate the clinical significance of long noncoding RNA (lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS) gene and its effects on Gemcitabine sensitivity in BUC.
Materials and Methods: The expression of CDKN2B-AS gene was examined with real-time quantitative PCR. The cell proliferation and the half maximal inhibitory concentration (IC50) of Gemcitabine were detected with enhanced CCK-8 assay. The apoptosis rate was examined using Annexin V-FITC/PI double-staining apoptosis kit. The protein expression was examined with western blotting. The activity of Wnt signaling pathway was examined with TOP/FOP luciferase assay.
Results: CDKN2B-AS gene was high-expressed in BUC tissues and J82, T24 cells compared with paracancerous normal urothelial tissues and SV-HUC-1 cells. Furthermore, the high-expression of CDKN2B-AS gene was related with high pathological grade and low Gemcitabine sensitivity of BUC tissues. The expression of CDKN2B-AS gene in Gemcitabine-resistant T24/Gem cells was much higher than that in T24 cells. Knockdown of CDKN2B-AS gene sensitized T24/Gem cells to Gemcitabine, promoted Gemcitabine-induced cytotoxicity. Knockdown of CDKN2B-AS gene inactivated Wnt signaling pathway, and Wnt signaling pathway mediated the effects on Gemcitabine sensitivity induced by CDKN2B-AS knockdown in T24/Gem cells.
Conclusion: LncRNA CDKN2B-AS is high-expressed in BUC and related to low Gemcitabine sensitivity of BUC. CDKN2B-AS inhibited Gemcitabine sensitivity through Wnt signaling pathway in BUC.
Keywords: long noncoding RNA, bladder urothelial carcinoma, CDKN2B antisense RNA 1, Wnt signaling pathway, chemotherapy