Sphingosine kinase 2 promotes colorectal cancer cell proliferation and invasion by enhancing MYC expression

Tumour Biol. 2016 Jun;37(6):8455-60. doi: 10.1007/s13277-015-4700-8. Epub 2016 Jan 5.

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and causes of cancer death in developed countries. SphK2 is overexpressed in a number of aggressive human carcinomas; however, the expression profile and potential function of SphK2 in CRC are still unknown. In this study, we investigated the SphK2 expression in tumoral tissue and the matched normal mucosae using quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. We also evaluated the impact of SphK2 knockdown on CRC cell proliferation and metastasis in vitro. SphK2 was significantly upregulated in CRC tissue as compared to the matched normal mucosae, and significant overexpression was found in the LoVo CRC cell line. SphK2 depletion by specific small interfering RNA (siRNA) in the CRC cell line was found to affect cell proliferation and cell migration. Our data suggest that the pathogenesis of CRC maybe mediated by SphK2, and SphK2 could represent a selective target for the molecularly targeted treatments of CRC.

Keywords: Colorectal cancer; Proliferation; Small interfering RNA; SphK2; Targeted therapy.

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Molecular Targeted Therapy / methods
  • Neoplasm Invasiveness
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Small Interfering / genetics*
  • Real-Time Polymerase Chain Reaction

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase 2, human