title: miR-144 reverses chemoresistance of hepatocellular carcinoma cell lines by targeting Nrf2-dependent antioxidant pathway.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Chemoresistance occurrence is a major cause of treatment failure in HCC. Currently, extensive research has revealed diverse mechanisms for chemoresistance, but the molecular mechanisms underlying the role of miRNAs in resistance to 5-FU are not confirmed in HCC cells. By quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we found that miR-144 was significantly decreased in HCC cell lines. It has been further demonstrated that miR-144 were significantly down-regulated in Bel-7402/5-FU cells compared with parental Bel-7402 cells by qRT-PCR and western blot. The expression of Nrf2 was reversely correlated to that of miR-144 in HCC cells. Moreover, Enhancement of 5-FU-induced cytotoxicity and apoptosis are resulted from the transfection with miR-144 mimics in Bel-7402/5-FU cells. Mechanically, miR-144 promoted nuclear factor erythroid-2-related factor-2 (Nrf2) mRNA degradation by directly targeting the Nrf2 3'untranslated region (3'UTR). In addition, ectopic expression of miR-144 in Bel-7402/5-FU cells reduced the levels of Nrf2 and inhibited the transcription of Nrf2-dependent HO-1 gene, thus contributing to 5-FU sensibilization. Conversely, re-expression of Nrf2 partly attenuated the chemosensibilization of miR-144. Our study showed that miR-144 serves as a potential chemoresistance-reversal agent in hepatocellular carcinoma cells, which is at least partly due to the down-regulation of Nrf2-dependent antioxidant pathway.
authors: Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors: Suna
authors: S
authors: Zhou
authors: Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors: Wenguang
authors: W
authors: Ye
authors: Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors: Yanjun
authors: Y
authors: Zhang
authors: Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors: Dequan
authors: D
authors: Yu
authors: Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors: Qiuju
authors: Q
authors: Shao
authors: Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors: Jun
authors: J
authors: Liang
authors: Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors: Mingxin
authors: M
authors: Zhang
keywords: Hepatocellular carcinoma; Nrf2; chemoresistance; miR-144