NORAD accelerates chemo-resistance of non-small-cell lung cancer via targeting at miR-129-1-3p/SOX4 axis

Qiang Huang1, Shijiang Xing2, Aiping Peng3

  • 1Department of Pharmacy, Affiliated Xiaolan Hospital of Southern Medical University, Zhongshan, China.

Bioscience Reports
|January 3, 2020
PubMed

Insights

The long non-coding RNA NORAD is upregulated in non-small cell lung cancer (NSCLC) and promotes cisplatin resistance. Targeting NORAD may restore sensitivity to chemotherapy in NSCLC patients.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) are implicated in cancer chemo-resistance.
  • The specific role of NORAD in non-small cell lung cancer (NSCLC) chemo-resistance is not well understood.

Purpose of the Study:

  • To investigate the function of NORAD in cisplatin (DDP) resistance in NSCLC.
  • To elucidate the underlying molecular mechanism of NORAD's action in NSCLC chemo-resistance.

Main Methods:

  • Utilized NSCLC cell lines (H446 and A549) with induced DDP resistance.
  • Assessed NORAD expression in DDP-resistant vs. sensitive NSCLC tissues and cells.
  • Performed NORAD knockdown and miR-129-1-3p overexpression experiments.
  • Investigated the interaction between NORAD, miR-129-1-3p, and its target SOX4.

Main Results:

  • NORAD expression was significantly higher in DDP-resistant NSCLC tissues and cells.
  • High NORAD expression correlated with poor prognosis in NSCLC patients.
  • NORAD knockdown resensitized NSCLC cells to DDP.
  • NORAD sponged miR-129-1-3p, which was downregulated in DDP-resistant cells.
  • Overexpression of miR-129-1-3p reduced DDP resistance.
  • SOX4 was identified as a downstream target of miR-129-1-3p, and its overexpression reversed the effect of NORAD knockdown.

Conclusions:

  • NORAD promotes DDP resistance in NSCLC by sponging miR-129-1-3p and upregulating SOX4.
  • The NORAD/miR-129-1-3p/SOX4 axis represents a potential therapeutic target for overcoming chemo-resistance in NSCLC.

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