Bioinformatic analysis reveals potential properties of human Claudin-6 regulation and functions

Oncol Rep. 2017 Aug;38(2):875-885. doi: 10.3892/or.2017.5756. Epub 2017 Jun 27.

Abstract

Claudin-6 (CLDN6) is an integral component of the tight junction proteins in polarized epithelial and endothelial cells and plays a crucial role in maintaining cell integrity. Deregulation of CLDN6 expression and distribution in tumor tissues have been widely documented and correlated with cancer progression and metastasis. However, a complete mechanistic understanding of CLDN6 regulation and function remains to be studied. Herein, we show new potential properties of CLDN6 regulation and functions from bioinformatics analysis. Using numerous algorithms to characterize the CLDN6 gene promoter elements and the CLDN6 protein structure, physio-chemical and localization properties, and its evolutionary relationships. CLDN6 is regulated by a diverse set of transcription factors (SP1, SPR, AML-1a, CdxA, CRE-BP and CREB) and associated with the levels of methylation of CpG islands in promoters. The structural properties of CLDN6 indicate that it promotes cancer cell behavior via the ASK1-p38/JNK MAPK secretory signaling pathway. In conclusion, this information from bioinformatics analysis will help future attempts to better understand CLDN6 regulation and functions.

MeSH terms

  • Claudins / genetics*
  • Computational Biology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Kinase Kinase 5 / genetics
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Promoter Regions, Genetic
  • Signal Transduction
  • Tight Junction Proteins / genetics*
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Claudins
  • Tight Junction Proteins
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 5
  • MAP3K5 protein, human
  • claudin 6