Journal of Cell Communication and Signaling

, Volume 13, Issue 1, pp 99–112 | Cite as

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

  • Li-li Wu
  • Wen-pin Cai
  • Xin Lei
  • Ke-qing Shi
  • Xiang-yang LinEmail author
  • Liang ShiEmail author
Research Article


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.

Key words

lncRNA· miR-340-5p· Nrf2· Cisplatin·chemoresistance· Hepatocellular carcinoma 



One-way analysis of variance


Hepatocellular carcinoma


Long noncoding RNA


Competitive endogenous RNA


Kelch-like ECH-associated protein 1

NFE2L2 or Nrf2

Nuclear factor erythroid 2-related factor2


Nrf2 regulation associated lncRNAs


Cell counting kit


Sodium dodecyl sulphate polyacrylamide gel electrophoresis


Real time quantitative reverse transcription PCR


RNA immunoprecipitation



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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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  1. 1.Department of Clinical Laboratory, The central hospital of WenzhouThe Dingli Clinical College of Wenzhou Medical UniversityWenzhouChina
  2. 2.Department of Clinical LaboratoryWenZhou Traditional Chinese Medicine HospitalWenzhouChina
  3. 3.The First Clinical College of Wenzhou Medical UniversityThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  4. 4.Department of Precision Medical Center LaboratoryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  5. 5.Department of Laboratory MedicineFuxue lane 2 The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  6. 6.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina

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