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MiR-760 enhances TRAIL sensitivity in non-small cell lung cancer via targeting the protein FOXA1

Xiang Zhang1, Lei Wang1, Yu Liu1

  • 1Department of Thoracic, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|April 19, 2018
PubMed

Insights

MicroRNA-760 (miR-760) is downregulated in non-small cell lung cancer (NSCLC). Restoring miR-760 enhances sensitivity to TNF-related apoptosis-inducing ligand (TRAIL) therapy by targeting FOXA1.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
  • TNF-related apoptosis-inducing ligand (TRAIL) shows potential as an anti-cancer therapeutic due to its tumor-specific cytotoxicity.
  • The role of microRNA-760 (miR-760) in NSCLC and its connection to TRAIL sensitivity are not well-defined.

Purpose of the Study:

  • To investigate the expression levels of miR-760 in NSCLC.
  • To elucidate the functional role of miR-760 in NSCLC cells.
  • To determine the relationship between miR-760, FOXA1, and TRAIL-induced apoptosis in NSCLC.

Main Methods:

  • Quantitative real-time PCR to assess miR-760 expression in NSCLC tissues and cell lines.
  • Transfection of NSCLC cells with miR-760 mimics or inhibitors.
  • Western blotting to analyze FOXA1 protein levels.
  • Cell viability assays and apoptosis assays to evaluate TRAIL sensitivity.

Main Results:

  • miR-760 was significantly downregulated in NSCLC tissues and cell lines compared to normal controls.
  • Ectopic expression of miR-760 enhanced NSCLC cell sensitivity to TRAIL-induced apoptosis.
  • miR-760 directly targeted the 3'-untranslated region of FOXA1, leading to reduced FOXA1 expression.
  • Silencing FOXA1 mimicked the effect of miR-760, sensitizing NSCLC cells to TRAIL and inhibiting proliferation.

Conclusions:

  • miR-760 functions as a tumor suppressor in NSCLC.
  • miR-760 enhances TRAIL sensitivity by negatively regulating the oncogene FOXA1.
  • These findings highlight miR-760 as a potential therapeutic target for improving TRAIL-based cancer treatments in NSCLC.
Keywords:
ApoptosisFOXA1NSCLCTRAILmiR-760

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