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Targeting MALAT1 induces DNA damage and sensitize non-small cell lung cancer cells to cisplatin by repressing BRCA1

Jinghua Huang1, Changxiu Lin2, Hai Dong3

  • 1Department of Radiation Oncology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin, China.

Cancer Chemotherapy and Pharmacology
|October 8, 2020
PubMed
Abstract

Insights

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates DNA repair in non-small cell lung cancer (NSCLC). Targeting MALAT1 induces DNA damage by affecting the BRCA1-mediated Homologous Recombination pathway, sensitizing NSCLC cells to cisplatin.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA implicated in DNA repair pathways.
  • Previous studies suggested MALAT1's role in alternative non-homologous end joining (A-NHEJ) in myeloma cells.

Purpose of the Study:

  • To investigate the function of MALAT1 in DNA repair mechanisms within non-small cell lung cancer (NSCLC).
  • To explore MALAT1's potential as a therapeutic target in NSCLC treatment.

Main Methods:

  • Co-immunoprecipitation and RNA pulldown assays to identify protein and microRNA interactions.
  • Bioinformatics, luciferase assays, and comet assays to confirm interactions and quantify DNA damage.
  • MTT and flow cytometry assays to assess cell viability and apoptosis.

Main Results:

  • MALAT1 participates in DNA repair pathways beyond A-NHEJ in NSCLC.
  • MALAT1 acts as a competing endogenous RNA (ceRNA) for miR-146a and miR-216b, upregulating BRCA1 expression.
  • Overexpression of MALAT1 confers resistance to cisplatin, while targeting MALAT1 sensitizes NSCLC cells to cisplatin by impairing the Homologous Recombination (HR) pathway.

Conclusions:

  • MALAT1 plays a crucial role in the HR pathway by stabilizing BRCA1 expression in NSCLC.
  • Targeting MALAT1 presents a potential therapeutic strategy to enhance cisplatin efficacy in NSCLC treatment by inducing DNA damage.
Keywords:
DNA repairLong non-coding RNAMALAT1Non-small cell lung cancermicroRNA

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