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

Autor: Lili Wu, Yifen Shi, Liang Shi, Xin Wei, Xiang-Yang Lin, Jian-Jian Zheng, Chenwei Pan
Rok vydání: 2018
Předmět:
0301 basic medicine
Keap1
Carcinoma
Hepatocellular
NF-E2-Related Factor 2
Hepatocellular carcinoma
lcsh:Medicine
Down-Regulation
Biology
Biochemistry
Long non-coding RNA (lncRNA)
03 medical and health sciences
0302 clinical medicine
Western blot
medicine
Humans
5-fluorouracil
lcsh:QH573-671
Receptor
Molecular Biology
Reporter gene
Kelch-Like ECH-Associated Protein 1
medicine.diagnostic_test
lcsh:Cytology
Cell growth
Competing endogenous RNA
Research
lcsh:R
Liver Neoplasms
RNA
Hep G2 Cells
Cell Biology
medicine.disease
digestive system diseases
Gene Expression Regulation
Neoplastic
miR-141
MicroRNAs
030104 developmental biology
Drug Resistance
Neoplasm
Cell culture
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Cancer research
RNA
Long Noncoding
Fluorouracil
Chemoresistance
Signal Transduction
Zdroj: Cell Communication and Signaling : CCS
Cell Communication and Signaling, Vol 16, Iss 1, Pp 1-15 (2018)
ISSN: 1478-811X
DOI: 10.1186/s12964-018-0260-z
Popis: Background 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. Methods 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. Results 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. Conclusions KRAL/miR-141/Keap1 axis mediates 5-fluorouracil resistance in HCC cell lines.
Databáze: OpenAIRE
Externí odkaz: