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基于表达谱和综合生物信息学分析的人类肿瘤中 COMMD6 的预后和调控机制。

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

机构信息

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangdong, Guangzhou, China.

Department of Radiation Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangdong, Guangzhou, China.

出版信息

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

DOI:10.1038/s41416-019-0571-x
PMID:31523056
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6889128/
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.

摘要

背景

铜代谢 MURR1（COMM）结构域家族已被报道在肿瘤发生中发挥重要作用。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

使用实时 PCR 和免疫组织化学检测 BALB/c 小鼠和人类组织中的 COMMD6 表达。Kaplan-Meier 分析用于评估 COMMD6 在肿瘤中的预后。基于癌症基因组图谱数据库中差异表达的 mRNAs、microRNAs 和长非编码 RNAs，构建竞争内源性 RNA（ceRNA）和转录调控网络。GO 和 KEGG 富集分析用于探索生物信息学意义。

结果

COMMD6 表达广泛存在于 BALB/c 小鼠和人类组织中，可预测癌症患者的预后。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，阐明了 COMMD6 在肿瘤中的潜在促瘤作用和机制。此外，COMMD6 可能调节 NF-κB 亚基的泛素化和降解，并调节肿瘤中的核糖核蛋白和剪接体复合物的生物发生。

结论

本研究可能有助于阐明 COMMD6 在人类肿瘤中的功能和机制，为肿瘤的预防和治疗提供潜在的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/f055f4c47fcf/41416_2019_571_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/53623ae1e321/41416_2019_571_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/a33143b070f1/41416_2019_571_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/3f368cf005ec/41416_2019_571_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/ad1a8bacf644/41416_2019_571_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/4cbde542d46c/41416_2019_571_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/f055f4c47fcf/41416_2019_571_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/53623ae1e321/41416_2019_571_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/a33143b070f1/41416_2019_571_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/3f368cf005ec/41416_2019_571_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/ad1a8bacf644/41416_2019_571_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/4cbde542d46c/41416_2019_571_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09de/6889128/f055f4c47fcf/41416_2019_571_Fig6_HTML.jpg

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