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Oncogene LSD1 is epigenetically suppressed by miR-137 overexpression in human non-small cell lung cancer

Xin Zhang1, Xiujuan Zhang1, Bo Yu1

  • 1Department of Respiration, Liaocheng People's Hospital, Liaocheng, 252000, China.

Biochimie
|February 23, 2017
PubMed
Abstract

Insights

MicroRNA-137 (miR-137) epigenetically regulates lysine-specific demethylase 1 (LSD1) to suppress non-small cell lung cancer (NSCLC) growth. This study shows miR-137 reverses LSD1-induced oncogenic effects in NSCLC.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • Non-small cell lung cancer (NSCLC) exhibits complex epigenetic dysregulation.
  • Lysine-specific demethylase 1 (KDM1A, also known as LSD1) is implicated in oncogenesis.
  • MicroRNA-137 (miR-137) is a known tumor suppressor microRNA.

Purpose of the Study:

  • To investigate the epigenetic regulation of microRNA-137 (miR-137) on lysine-specific demethylase 1 (LSD1) and its role in non-small cell lung cancer (NSCLC).
  • To elucidate the mechanism by which miR-137 counteracts LSD1-induced oncogenic effects in NSCLC cells.

Main Methods:

  • Overexpression of LSD1 in NSCLC cell lines (A549, H460) and assessment of its effects on cell proliferation and migration.
  • Upregulation of miR-137 in LSD1-overexpressing NSCLC cells using lentiviral transfection.
  • Analysis of KDM1A/LSD1 expression, proliferation, migration, and key histone deacetylase-associated pathway components (EZH2, HDAC1, HDAC2) via qRT-PCR and Western blot.

Main Results:

  • LSD1 overexpression promoted NSCLC proliferation and migration by upregulating KDM1A and LSD1 protein.
  • miR-137 upregulation inversely correlated with LSD1, suppressing KDM1A/LSD1 expression and inhibiting cancer cell proliferation and migration.
  • LSD1 activated EZH2, HDAC1, and HDAC2, while miR-137 inhibited these targets in NSCLC cells.

Conclusions:

  • Oncogenic effects of LSD1 in NSCLC are reversely regulated by its upstream epigenetic modulator, miR-137.
  • The interaction between LSD1 and miR-137 likely involves the modulation of histone deacetylase-associated signaling pathways.
Keywords:
BiochemistryLSD1Lung cancerMiR-137NSCLCWestern blot

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