TSPAN31 is a critical regulator on transduction of survival and apoptotic signals in hepatocellular carcinoma cells

FEBS Lett. 2017 Sep;591(18):2905-2918. doi: 10.1002/1873-3468.12737. Epub 2017 Sep 7.


Tetraspanins are commonly believed to act as 'molecular facilitators', not directly involved in signal transduction. Tetraspanin 31 (TSPAN31), recently discovered to be linked to cancer, has not yet been studied in hepatocellular carcinoma (HCC). Here, we show that TSPAN31 is the natural antisense transcript of cyclin dependent kinase 4 (CDK4), and regulates the expression of CDK4 mRNA and protein. Target analysis indicates that miR-135b can directly regulate TSPAN31 expression. miR-135b-induced TSPAN31 silencing increases CDK4 protein levels. Interestingly, p53 negatively regulates TSPAN31 expression. siRNA-induced TSPAN31 knockdown reduces the expression of Akt signaling pathway components phosphorylated Akt, p-GSK3β and β-catenin, and restrains β-catenin migration to cell nucleus. TSPAN31 knockdown also significantly inhibits HCC cell invasion and migration. These findings thus point to TSPAN31 as a novel regulator in transduction of intracellular survival and apoptotic signals.

Keywords: TSPAN31; apoptotic; hepatocellular carcinoma cell; signal transduction; survival.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Fluorescent Antibody Technique
  • Humans
  • Immunoprecipitation
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Tetraspanins / genetics
  • Tetraspanins / metabolism*


  • MIRN135 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • TSPAN31 protein, human
  • Tetraspanins
  • Proto-Oncogene Proteins c-akt