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

被引:102
|
作者
Fang, Qun [1 ,2 ]
Chen, XiaoYan [3 ]
Zhi, XuTing [1 ]
机构
[1] Shandong Univ, Dept Gen Surg, Qilu Hosp, Jinan, Shandong, Peoples R China
[2] Yidu Cent Hosp Weifang, Dept Emergency, Qingzhou, Shandong, Peoples R China
[3] Women & Childrens Hosp Linyi, Dept Clin Lab, Linyi, Shandong, Peoples R China
来源
MEDICAL SCIENCE MONITOR | 2016年 / 22卷
关键词
Genes; MDR; MicroRNAs; RNA; Long Noncoding; Stomach Neoplasms; CISPLATIN SENSITIVITY; CELLS; EXPRESSION; IDENTIFICATION; ADRIAMYCIN; PROMOTES;
D O I
10.12659/MSM.900688
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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/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 UCA1 restored miR-27b expression in gastric cancer cells. The UCA1-miR-27b axis was involved in regulation of chemosensitivity of gastric cancer cells.
引用
收藏
页码:3506 / 3513
页数:8
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