Downregulation of SMC1A inhibits growth and increases apoptosis and chemosensitivity of colorectal cancer cells

J Int Med Res. 2016 Feb;44(1):67-74. doi: 10.1177/0300060515600188. Epub 2015 Dec 3.

Abstract

Objective: The structural maintenance of chromosomes (SMC) 1A protein is a component of the cohesin multiprotein complex that is essential for sister chromatid cohesion. SMC1A gene mutations have been reported in colorectal cancer. This study aimed to investigate the role of SMC1A gene expression in colorectal cancer in vitro.

Methods: SMC1A gene expression was silenced by lentivirus-mediated infection with small interfering RNA (siRNA) in the human colorectal cancer cell line HT-29. Cell proliferation rates, SMC1A mRNA and protein levels, apoptosis and chemosensitivity to oxaliplatin were evaluated using routine in vitro assays, real-time polymerase chain reaction, Western blotting and flow cytometry.

Results: Knockdown of SMC1A protein and mRNA levels resulted in the inhibition of cell proliferation, an increased rate of apoptosis and enhanced chemosensitivity to oxaliplatin in HT-29 cells.

Conclusions: The findings of this study suggest that SMC1A plays an oncogenic role in colorectal cancer and that it might be a promising target for colorectal cancer therapy.

Keywords: SMC1A; Structural maintenance of chromosomes 1A protein; chemosensitivity; colorectal cancer; oxaliplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Cycle
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Down-Regulation / drug effects*
  • Down-Regulation / genetics
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Lentivirus / metabolism
  • Organoplatinum Compounds / pharmacology*
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Organoplatinum Compounds
  • structural maintenance of chromosome protein 1
  • Oxaliplatin