3 years ago

lncRNA KRAL reverses 5-fluorouracil resistance in hepatocellular carcinoma cells by acting as a ceRNA against miR-141

Xiangyang Lin, Lili Wu, Jianjian Zheng, Yifen Shi, Chenwei Pan, Xin Wei, Liang Shi



5-Fluorouracil (5-FU) has been widely applied to treat various types of cancers, including hepatocellular carcinoma (HCC). However, primary or acquired 5-FU resistance prevents the clinical application of this drug in cancer therapy. Herein, our study is the first to demonstrate that lower expression of KRAL, a long non-coding RNA (lncRNA), mediates 5-FU resistance in HCC via the miR-141/Keap1 axis.


Cell proliferation assays, western blot analysis, qRT-PCR, the dual-luciferase reporter assay and RNA immunoprecipitation were performed to investigate the mechanisms by which KRAL mediates 5-fluorouracil resistance in HCC cell lines.


The quantitative analysis indicated that KRAL and Keap1 were significantly decreased and that Nrf2 was increased in HepG2/5-FU and SMMC-7721/5-FU cells compared with the corresponding expression levels in the respective parental cells. Overexpression of KRAL increased Keap1 expression, and inactivating the Nrf2-dependent antioxidant pathway could reverse the resistance of HepG2/5-FU and SMMC-7721/5-FU cells to 5-FU. Moreover, KRAL functioned as a competitive endogenous RNA (ceRNA) by effectively binding to the common miR-141 and then restoring Keap1 expression. These findings demonstrated that KRAL is an important regulator of Keap1; furthermore, the ceRNA network involving KRAL may serve as a treatment strategy against 5-FU resistance in hepatocellular carcinoma cells.


KRAL/miR-141/Keap1 axis mediates 5-fluorouracil resistance in HCC cell lines.

Publisher URL: https://link.springer.com/article/10.1186/s12964-018-0260-z

DOI: 10.1186/s12964-018-0260-z

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