Abstract
BackgroundThe 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.MethodsCOMMD6 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.ResultsCOMMD6 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.ConclusionsThis study may help to elucidate the functions and mechanisms of COMMD6 in human tumours, providing a potential biomarker for tumour prevention and therapy.
Highlights
The Copper Metabolism MURR1 (COMM) domain family has been reported to play important roles in tumorigenesis
The activation of NF-κB could be completely abolished by the mutation of the amino acid residues Trp[24] and Pro[41] in the COMM domain of COMMD6.21 Aberrant activation of the NF-κB signalling pathway has been observed in many human cancers, which induce tumour infinite growth and progression.[22]
Construction of transcriptional network of COMMD6 in CHOL To further explore the potential upstream mechanism of COMMD6 involved in tumour progression, we presented a transcriptional regulatory network and 62 transcription factors (TFs) that participate in the regulation of COMMD6 expression (Fig. 5a)
Summary
The incidence and mortality of cancer are rapidly growing worldwide. The global cancer burden is further aggravated with an estimated 18.1 million new cancer cases and 9.6 million cancer deaths in 2018, being the leading cause of death. M Yang et al.[700] adenocarcinoma by decreasing MMP2 secretion.[14] COMMD9 promotes TFDP1/E2F1 activation and progression of non-small cell lung cancer by interaction with TFDP1.15 we have previously shown the expression profiles of COMMD10 in human tumours[16] and found that COMMD10 inhibits the invasion and metastasis of colorectal cancer by promoting ubiquitination and degradation of NF-kB.[17] As a prototype for the COMMD family, COMMD6 was primarily formed by the COMM domain, a region of the COMMD proteins that is crucial for multiple biological functions.[18] COMMD6 from amphioxus Branchiostoma belcheri forms a heterodimer with creatine kinase, leading to inhibition of creatine kinase activity and energy conversion.[19] COMMD6 colocalises with the WASH complex and retromer in sub-compartment of the endosome and participates in the CCC-WASH axis in endosomal sorting of receptors.[20] COMMD6 has been reported to be involved in the inhibition of NF-κB pathway activity in HEK-293 cells. We provided the expression profile data and bioprediction information of COMMD6 in a variety of tissues, which help to elucidate its functions and clinical values in various human tumours
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