siRNA-mediated suppression of collagen type iv alpha 2 (COL4A2) mRNA inhibits triple-negative breast cancer cell proliferation and migration

Oncotarget. 2017 Jan 10;8(2):2585-2593. doi: 10.18632/oncotarget.13716.

Abstract

Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. Collagen type IV alpha 2 (COL4A2), a major component of the basement membrane, dynamically influences a wide range of biological processes, including cancer pathogenesis and progression. This study evaluated the effects of COL4A2 siRNA delivered by lentiviral vector to TNBC cells. COL4A2 siRNA lenti-viral vector was constructed and transfected into MDA-MB-231 and MDA-MB-468 cells. The COL4A2 mRNA levels were quantified by RT-PCR. CCK8 assay was performed to evaluate cell proliferation and migration. Cell migration and invasion assays were carried out using Transwell. Cell apoptosis and cell cycle analyses were conducted using flow cytometric approach. We found that COL4A2 mRNA levels were significantly down-regulated in MDA-MB-231 and MDA-MB-468 cells after transfection with COL4A2 siRNA. Furthermore, cell migration and proliferation were significantly decreased and the cell cycle was arrested. Our results indicated that COL4A2 siRNA significantly suppresses the migration and proliferation of TNBC cells. Inhibition of COL4A2 may be a new target for the prevention and treatment of TNBC.

Keywords: COL4A2; lentiviral vector; small interfering RNA (siRNA); triple-negative breast cancer (TNBC).

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Collagen Type IV / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • RNA, Small Interfering / pharmacology*
  • Triple Negative Breast Neoplasms / genetics*
  • Up-Regulation

Substances

  • COL4A2 protein, human
  • Collagen Type IV
  • RNA, Small Interfering