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NRAL mediates cisplatin resistance in hepatocellular carcinoma via miR-340-5p/Nrf2 axis

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Journal of Cell Communication and Signaling Aims and scope

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Abstract

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.

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Abbreviations

ANOVA:

One-way analysis of variance

HCC:

Hepatocellular carcinoma

lncRNA:

Long noncoding RNA

ceRNA:

Competitive endogenous RNA

Keap1:

Kelch-like ECH-associated protein 1

NFE2L2 or Nrf2:

Nuclear factor erythroid 2-related factor2

NRAL:

Nrf2 regulation associated lncRNAs

CCK-8:

Cell counting kit

SDS-PAGE:

Sodium dodecyl sulphate polyacrylamide gel electrophoresis

qRT-PCR:

Real time quantitative reverse transcription PCR

RIP:

RNA immunoprecipitation

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Acknowledgments

This project was supported by the Natural Science Foundation of China (81501823 ), Zhejiang Provincial Natural Science Foundation of China (LY18H160049, LY17H200005 and LY16H160047), Zhejiang Provincial Medical and Health Research Project(2017KY459), Wenzhou municipal Science and Technology Bureau (Y20160077and Y20160071 ).

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Author notes

  1. Li-li Wu, Wen-pin Cai and Xin Lei contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, The central hospital of Wenzhou, The Dingli Clinical College of Wenzhou Medical University, Wenzhou, China

    Li-li Wu

  2. Department of Clinical Laboratory, WenZhou Traditional Chinese Medicine Hospital, Wenzhou, China

    Wen-pin Cai

  3. The First Clinical College of Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Xin Lei

  4. Department of Precision Medical Center Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Ke-qing Shi

  5. Department of Laboratory Medicine, Fuxue lane 2 The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China

    Xiang-yang Lin & Liang Shi

  6. Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Ke-qing Shi & Liang Shi

Authors
  1. Li-li Wu
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  2. Wen-pin Cai
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  3. Xin Lei
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  4. Ke-qing Shi
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  5. Xiang-yang Lin
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  6. Liang Shi
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Corresponding authors

Correspondence to Xiang-yang Lin or Liang Shi.

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Wu, Ll., Cai, Wp., Lei, X. et al. NRAL mediates cisplatin resistance in hepatocellular carcinoma via miR-340-5p/Nrf2 axis. J. Cell Commun. Signal. 13, 99–112 (2019). https://doi.org/10.1007/s12079-018-0479-x

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  • DOI: https://doi.org/10.1007/s12079-018-0479-x

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