Prognosis and modulation mechanisms of COMMD6 in human tumours based on expression profiling and comprehensive bioinformatics analysis

Br J Cancer. 2019 Oct;121(8):699-709. doi: 10.1038/s41416-019-0571-x. Epub 2019 Sep 16.

Abstract

Background: The Copper Metabolism MURR1 (COMM) domain family has been reported to play important roles in tumorigenesis. As a prototype for the COMMD family, the expression pattern and biological function of COMMD6 in human tumours remain unknown.

Methods: COMMD6 expression in BALB/c mice and human tissues was examined using real-time PCR and immunohistochemistry. Kaplan-Meier analysis was applied to evaluate the prognosis of COMMD6 in tumours. Competing endogenous RNA (ceRNA) and transcriptional regulation network were constructed based on differentially expressed mRNAs, microRNAs and long non-coding RNAs from the cancer genome atlas database. GO and KEGG enrichment analysis were used to explore the bioinformatics implication.

Results: COMMD6 expression was widely observed in BALB/c mice and human tissues, which predicted prognosis of cancer patients. Furthermore, we shed light on the underlying tumour promoting role and mechanism of COMMD6 by constructing a TEX41-miR-340-COMMD6 ceRNA network in head and neck squamous cell carcinoma and miR-218-CDX1-COMMD6 transcriptional network in cholangiocarcinoma. In addition, COMMD6 may modulate the ubiquitination and degradation of NF-κB subunits and regulate ribonucleoprotein and spliceosome complex biogenesis in tumours.

Conclusions: This study may help to elucidate the functions and mechanisms of COMMD6 in human tumours, providing a potential biomarker for tumour prevention and therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Bile Duct Neoplasms
  • Breast / metabolism
  • Cell Line, Tumor
  • Cholangiocarcinoma
  • DNA Copy Number Variations
  • DNA Methylation
  • Female
  • Gastrointestinal Tract / metabolism
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Head and Neck Neoplasms
  • Homeodomain Proteins / genetics
  • Humans
  • Immunohistochemistry
  • Kidney / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • Mutation
  • NF-kappa B / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Phylogeny
  • Placenta / metabolism
  • Pregnancy
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / metabolism
  • Ribonucleoproteins
  • Spliceosomes
  • Squamous Cell Carcinoma of Head and Neck
  • Transcriptome
  • Uterus / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CDX1 protein, human
  • COMMD6 protein, human
  • Commd6 protein, mouse
  • Homeodomain Proteins
  • MIRN218 microRNA, human
  • MIRN340 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Long Noncoding
  • RNA, Messenger
  • Ribonucleoproteins