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

Li-Li Wu1, Wen-Pin Cai2, Xin Lei3

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

Journal of Cell Communication and Signaling
|July 22, 2018
PubMed

Insights

A novel long non-coding RNA, NRAL, promotes cisplatin resistance in hepatocellular carcinoma (HCC) by regulating the miR-340-5p/Nrf2 pathway. Depleting NRAL sensitizes liver cancer cells to chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) are implicated in hepatocellular carcinoma (HCC) pathogenesis.
  • The precise mechanisms of drug resistance in liver cancer cells, particularly concerning lncRNAs, remain incompletely understood.

Purpose of the Study:

  • To identify and characterize novel lncRNAs involved in cisplatin resistance in HCC.
  • To elucidate the molecular mechanism by which NRAL influences chemotherapy response in liver cancer.

Main Methods:

  • Screening of differentially expressed lncRNAs in parental and cisplatin-resistant HCC cell lines (HepG2 and HepG2/CDDP).
  • Functional assays involving NRAL depletion to assess its impact on chemosensitivity and apoptosis.
  • Investigation of the NRAL/miR-340-5p/Nrf2 regulatory axis using molecular biology techniques.

Main Results:

  • A novel lncRNA, NRAL (Nrf2 regulation-associated lncRNA), was identified and found to be highly expressed in cisplatin-resistant HCC cells.
  • NRAL depletion significantly increased cisplatin-induced cytotoxicity and apoptosis in resistant HCC cell lines.
  • NRAL functions as a competing endogenous RNA (ceRNA) for miR-340-5p, thereby regulating Nrf2 expression and influencing the response to cisplatin.

Conclusions:

  • The NRAL/miR-340-5p/Nrf2 axis is a key mediator of cisplatin resistance in hepatocellular carcinoma.
  • NRAL represents a potential therapeutic target for overcoming drug resistance in HCC treatment.
Keywords:
lncRNA· miR-340-5p· Nrf2· Cisplatin·chemoresistance· Hepatocellular carcinoma

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