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  • Title: miR-503-5p confers drug resistance by targeting PUMA in colorectal carcinoma.
    Author: Xu K, Chen G, Qiu Y, Yuan Z, Li H, Yuan X, Sun J, Xu J, Liang X, Yin P.
    Journal: Oncotarget; 2017 Mar 28; 8(13):21719-21732. PubMed ID: 28423513.
    Abstract:
    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.
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