Open AccessNRAL mediates cisplatin resistance in hepatocellular carcinoma via miR‐340‐5p/Nrf2 axis
Author(s) -
Wu Lili,
Cai Wenpin,
Lei Xin,
Shi Keqing,
Lin Xiangyang,
Shi Liang
Publication year - 2018
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-018-0479-x
Subject(s) - cisplatin , competing endogenous rna , hepatocellular carcinoma , cancer research , apoptosis , liver cancer , microrna , cell culture , drug resistance , long non coding rna , cytotoxicity , phenotype , cell , biology , cancer , medicine , downregulation and upregulation , gene , in vitro , chemotherapy , genetics
Recent studies have shown that long non‐coding RNAs (lncRNAs) play a pivotal role in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the biological action and potential mechanism of liver cancer cell drug resistance have not been clearly clarified. In this study, lncRNAs were screened and differentially expressed in parental and cisplatin‐resistant cell lines (HepG2 and HepG2/CDDP). A novel lncRNA, termed NRAL (Nrf2 regulation‐associated lncRNA), was identified, and the initial results indicated that it was highly expressed in HepG2 cisplatin resistant cell lines compared to their parental counterparts. Functionally, NRAL depletion significantly enhanced CDDP‐mediated cytotoxicity and apoptosis in two cisplatin‐resistant HCC cell lines. Mechanistically, the results indicated that NRAL regulates Nrf2 expression through miR‐340‐5p serving as a competing endogenous RNA (ceRNA), thus influencing the CDDP‐induced phenotype in HCC. Collectively, the present investigation suggest that the NRAL/miR‐340‐5p/Nrf2 axis mediates cisplatin resistance in HCC, which may provide novel targets for overcoming cisplatin resistance in hepatocellular carcinoma cells.