Knockdown of GRHL3 inhibits activities and induces cell cycle arrest and apoptosis of human colorectal cancer cells

J Huazhong Univ Sci Technolog Med Sci. 2017 Dec;37(6):880-885. doi: 10.1007/s11596-017-1821-x. Epub 2017 Dec 21.

Abstract

The Grainyhead-like 3 (GRHL3) is involved in epidermal barrier formation, neural tube closure and wound repair. Previous studies have suggested that GRHL3 has been linked to many different types of cancers. However, to date, its effects on human colorectal cancer (CRC) has not been clarified yet. Our microarray analysis has indicated predominant GRHL3 expression in CRC. The purpose of this study was to investigate the expression and significance of GRHL3 in CRC tumorigenesis using CRC tissues and paired paracancerous tissues, as well as using distinct CRC cell lines (HT29 and DLD1). We observed increased GRHL3 expression at both mRNA and protein levels in CRC tissues and CRC cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Moreover, silencing GRHL3 with siRNA could suppress CRC cell proliferation, viability and migration in vitro. We also found that knockdown of GRHL3 could promote cell cycle arrest at G0/G1 phase in HT29 cells and DLD1 cells, and induce cell apoptosis in HT29 cells. Together, our study revealed the down-regulation of GRHL3 in vitro could inhibit CRC cell activity and trigger cell cycle arrest at G0/G1 phase and apoptosis.

Keywords: Grainyhead-like 3; apoptosis; cell cycle; colorectal cancer; migration; proliferation.

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle Checkpoints / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Microarray Analysis
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • GRHL3 protein, human
  • RNA, Small Interfering
  • Transcription Factors