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Long Non-Coding RNA (LncRNA) Urothelial Carcinoma Associated 1 (UCA1) Increases Multi-Drug Resistance of Gastric Cancer via Downregulating miR-27b

作者:Qun Fang, XiaoYan Chen, Xu–Ting Zhi · 发表于:Medical Science Monitor · 年份:2016 · DOI:10.12659/msm.900688 · 被引用次数:113 · 研究领域:Cancer-related molecular mechanisms research、Circular RNAs in diseases、MicroRNA in disease regulation

BACKGROUND In this study, we aimed to investigate the association between UCA1 and miR-27b in gastric cancer and further study their involvement in multi-drug resistance (MDR) of gastric cancer. MATERIAL AND METHODS The microarray data of dysregulated lncRNAs in gastric cancer tissues was retrieved in the GEO dataset. QRT-PCR analysis was performed to assess UCA1 expression based on 28 paired cancerous and peritumoral normal tissues. The human gastric cancer cell line SGC-7901, and SGC-7901 derived Adriamycin (doxorubicin) resistant SGC-7901/ADR, cisplatin resistant SGC-7901/DDP, and 5-FU resistant SGC-7901/FU cells were used as in vitro cell models to assess the effect of UCA1 and miR-27b on MDR. RESULTS UCA1 was significantly upregulated in the cancerous tissues and its expression was negatively correlated with miR-27b expression level. Inhibition of UCA1 significantly restored miR-27b expression in MDR gastric cancer cells. UCA1 knockdown and miR-27b overexpression reduced IC50 of ADR, DDP, and 5-FU in SGC-7901/ADR cells and increased ADR induced cell apoptosis. UCA1 overexpression and miR-27b inhibition increased the IC50 of ADR, DDP, and 5-FU in SGC-7901 cells and reduced ADR induced cell apoptosis. Western blot analysis showed that UCA1 knockdown and miR-27b overexpression also decreased anti-apoptotic protein BCL-2 and increased apoptotic protein cleaved caspase-3. CONCLUSIONS UCA1 is negatively correlated with miR-27b expression in gastric cancer tissue. Knockdown of ...