Inhibition of SALL4 suppresses carcinogenesis of colorectal cancer via regulating Gli1 expression

Int J Clin Exp Pathol. 2015 Sep 1;8(9):10092-101. eCollection 2015.

Abstract

Background: SALL4 is a novel oncogene mediating tumorigenesis in multiple carcinomas. However, its actual role and mechanisms participating in the development of colorectal cancer remains unclear.

Methods: Immunohistochemical staining and Western blot were conducted to detect the expression of SALL4 and other molecules. siRNA of SALL4 was transfected to silence SALL4 expression in Caco-2 cell line. Flow cytometry was used for cell cycle and apoptosis analysis. Wound healing and transwell assay were used for invasion test. CCK-8 test was employed for cell proliferation and drug sensitivity assessment.

Results: By inhibition of SALL4 expression, the proliferation, invasiveness and drug resistance were dramatically reduced while apoptosis rate was up-regulated. Gli1 was found to decrease its expression in SALL4 silencing cells. Moreover, the inhibition on tumorigenesis of Caco-2 by SALL4 silencing was antagonized by Gli1 up-regulation, suggesting Gli1 as a downstream target of SALL4 in cancer development.

Conclusion: SALL4 inhibition limited oncogenesis on colorectal cancer by reducing Gli1 expression.

Keywords: Gli1; SALL4; carcinogenesis; colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Caco-2 Cells
  • Carcinogenesis / genetics*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Zinc Finger Protein GLI1

Substances

  • GLI1 protein, human
  • SALL4 protein, human
  • Transcription Factors
  • Zinc Finger Protein GLI1