Prognosis and modulation mechanisms of COMMD6 in human tumours based on expression profiling and comprehensive bioinformatics analysis
Prognosis and modulation mechanisms of COMMD6 in human tumours based on expression profiling and comprehensive bioinformatics analysis
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基于表达谱和综合生物信息学分析的 COMMD6 在人类肿瘤中的预后和调节机制
DOI：
10.1038/s41416-019-0571-x
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发表时间：
2019-10-15
影响因子：
8.8
通讯作者：
Guan, Jian
中科院分区：
文献类型：
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作者：
Yang, Mi;Huang, Weiqiang;Guan, Jian
铜代谢MURR1 （COMM）结构域家族已被报道在肿瘤发生中起重要作用。作为COMMD家族的原型，COMMD6在人类肿瘤中的表达模式和生物学功能尚不清楚。方法采用实时荧光定量PCR和免疫组织化学方法检测commd6在BALB/c小鼠和人组织中的表达。应用Kaplan-Meier分析评价COMMD6在肿瘤中的预后。基于肿瘤基因组图谱数据库中差异表达的mrna、microrna和长链非编码RNA，构建了竞争性内源RNA （ceRNA）和转录调控网络。利用GO和KEGG富集分析探讨其生物信息学意义。结果commd6在BALB/c小鼠和人体组织中广泛表达，可预测肿瘤患者的预后。此外，我们通过构建头颈部鳞状细胞癌中的TEX41-miR-340-COMMD6 ceRNA网络和胆管癌中的miR-218-CDX1-COMMD6转录网络，揭示了COMMD6潜在的促瘤作用和机制。此外，COMMD6可能调节NF-κB亚基的泛素化和降解，调节肿瘤中的核糖核蛋白和剪接体复合体的生物发生。结论本研究有助于阐明COMMD6在人类肿瘤中的功能和机制，为肿瘤防治提供潜在的生物标志物。
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.