The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma. (1st November 2017)

• Record Type: Journal Article
• Authors: Zhao, Yang; Qi, Xinming; Chen, Jing; Wei, Wenxin; Yu, Cunzhi; Yan, Hong; Pu, Mengfan; Li, Yu; Miao, Lingling; Li, Chunzhu; Ren, Jin
• Is Part Of: Cancer letters. Volume 408(2017)
• Page Start: 102
• Page End: 111
• Publication Date: 2017-11-01
• Subjects: Hepatocellular carcinoma -- ABCB1 -- Sp3 -- miR-491-3p -- Multidrug resistance; HCC hepatocellular carcinoma -- MDR multidrug resistance -- 3′-UTR 3′ untranslated region -- NC negative control oligonucleotides -- Ctrl control -- wt wild-type -- mt mutant; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.08.027
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: As one of main obstacles in the treatment and prognosis of hepatocellular carcinoma (HCC), multidrug resistance (MDR) is usually associated with the overexpression of the drug efflux pump P-glycoprotein (P-gp/ABCB1) which is responsible for reducing the intracellular concentration of chemotherapeutic agents. In current work, we discovered the novel role of miR-491-3p in ABCB1-mediated multidrug resistance in HCC and revealed the underlying mechanism in which miR-491-3p downregulated the expression of ABCB1 and its transcription factor Sp3 by directly targeting their 3′-UTR. Moreover, overexpressing ABCB1 or Sp3 reversed the sensitivity to chemotherapeutics in Hep3B cells induced by miR-491-3p, confirming miR-491-3p/Sp3/ABCB1 regulatory loop plays an important role in enhancing the drugs sensitivity of HCC. Meanwhile, the discovery of that the expression level of miR-491-3p was inversely correlated with that of ABCB1 and Sp3 in HCC cell lines and clinical samples pointed out the possibility of miR-491-3p in clinical use. In summary, our results reveal a pivotal role of miR-491-3p in the regulation of MDR in HCC, and suggest the potential application of miR-491-3p as a therapeutic strategy for modulating MDR in cancer cells. Highlights: MiR-491-3p inhibits both post-transcriptional level and transcriptional level of ABCB1. The miR-491-3p/ABCB1/Sp3 regulatory loop increases the sensitivity of HCC cells to chemotherapeutics. New therapeutic strategies targeted on the miR-491-3p/ABCB1/Sp3 axis may enhance the efficacy of chemotherapy against HCC.