文献类型：期刊文献

英文题名：miR-503-5p confers drug resistance by targeting PUMA in colorectal

作者：Xu, Ke[1,2];Chen, Guo[3,4];Qiu, Yanyan[1,2,5];Yuan, Zeting[1];Li, Hongchang[5];Yuan, Xia[6];Sun, Jian[1,2];Xu, Jianhua[2];Liang, Xin[7,8];Yin, Peihao[2,5]

机构：[1]Shanghai Univ Tradit Chinese Med, Cent Lab, Putuo Hosp, Shanghai 200062, Peoples R China;[2]Shanghai Univ Tradit Med, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China;[3]Emory Univ, Dept Radiat Oncol, Sch Med, Atlanta, GA 30322 USA;[4]Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA;[5]Shanghai Univ Tradit Chinese Med, Dept Gen Surg, Putuo Hosp, Shanghai 200062, Peoples R China;[6]Shanghai Univ Tradit Chinese Med, Dept Pharm, Putuo Hosp, Shanghai 200062, Peoples R China;[7]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[8]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2017

卷号：8

期号：13

起止页码：21719

外文期刊名：ONCOTARGET

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000397642400099)】；

基金：This work was supported by the National Natural Science Foundation of China (No. 81503434; No. 81502540; No. 81473482) and "the twelfth five year" key subject (Integrated Chinese and Western Medicine) of traditional Chinese medicine of State Administration of Traditional Chinese medicine.

语种：英文

外文关键词：colorectal carcinoma; multidrug-resistance; miR-503-5p; PUMA; p53

摘要：The development of multidrug-resistance (MDR) is a major contributor to death in colorectal carcinoma (CRC). Here, we investigated the possible role of microRNA (miR)-503-5p in drug resistant CRC cells. Unbiased microRNA array screening revealed that miR-503-5p is up-regulated in two oxaliplatin (OXA)-resistant CRC cell lines. Overexpression of miR-503-5p conferred resistance to OXA-induced apoptosis and inhibition of tumor growth in vitro and in vivo through down-regulation of PUMA expression. miR-503-5p knockdown sensitized chemoresistant CRC cells to OXA. Our studies indicated that p53 suppresses miR-503-5p expression and that deletion of p53 upregulates miR-503-5p expression. Inhibition of miR-503-5p in p53 null cells increased their sensitivity to OXA treatment. Importantly, analysis of patient samples showed that expression of miR-503-5p negatively correlates with PUMA in CRC. These results indicate that a p53/miR-503-5p/PUMA signaling axis regulates the CRC response to chemotherapy, and suggest that miR-503-5p plays an important role in the development of MDR in CRC by modulating PUMA expression.