Expression profile and bioinformatics analysis of COMMD10 in BALB/C mice and human
Expression profile and bioinformatics analysis of COMMD10 in BALB/C mice and human
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COMMD10 在 BALB/C 小鼠和人类中的表达谱和生物信息学分析
DOI：
10.1038/s41417-019-0087-9
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发表时间：
2020-04-01
影响因子：
6.4
通讯作者：
Guan, Jian
中科院分区：
文献类型：
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作者：
Fan, Yao;Zhang, Longshan;Guan, Jian
COMMD 10是COMMD蛋白的成员之一，已被证实能靶向p65核因子-κ B（nuclear factor-kappaB）亚基，减少其核转位，从而导致NF-kappaB通路失活，抑制结直肠癌的侵袭和转移。本研究旨在探讨其在人体正常组织和其他肿瘤组织中的表达模式和组织分布，并探讨其相关机制。本研究首次提供了COMMD 10在BALB/c小鼠不同组织中的表达谱和组织学分布，并鉴定了COMMD 10在人体不同正常组织和肿瘤组织中的生物学分布。我们使用TCGA数据库验证COMMD 10的表达谱。用STRING方法预测COMMD 10的互作基因。最后进行数据库分析，利用miRDB、miRWalk、TargetScan和microRNA对靶向COMMD 10的microRNA进行预测。通过GO和KEGG通路分析来预测COMMD 10及其相互作用基因的生物学功能。COMMD 10在肺和脾中的表达量最高，在心和脑中的表达量最低。免疫组化检测发现COMMD 10在不同组织中均有不同程度的表达，主要定位于胞浆。随后，我们发现COMMD 10在不同的人正常组织中显示不同程度的表达，主要位于细胞质中，而肝细胞COMMD 10则位于细胞核和细胞质中。除乳腺小细胞癌、乳腺叶状肿瘤、肺腺癌、胸腺瘤、宫颈癌和膀胱尿路上皮癌外，其余肿瘤组织COMMD 10均为胞浆阳性。Kaplan-Meier回归分析显示COMMD 10表达水平升高的肾透明细胞癌患者生存期延长。STRING数据库显示COMMD 10有41个相互作用的基因，4个不同数据库的数据表明hsa-miR-590- 3 p可能是COMMD 10的潜在调控因子。GO分析表明COMMD 10及其相互作用基因主要富集于Cullin-RING泛素连接酶复合物、铜离子的结合和转运、铜离子的转运和稳态维持、蛋白质的转录、翻译和转运，并负调控NF-κ B转录因子的活性。KEGG通路显示COMMD 10及其相互作用基因主要参与肾细胞癌、HIF-1信号通路、泛素化介导的蛋白水解、内吞和矿物质吸收。COMMD 10可能通过miR-590- 3 p-COMMD 10-Cul 2-RBX 1-NF-κB/HIF/NRF 2通路在肾透明细胞癌中发挥抑瘤作用，并调节多种肿瘤细胞对顺铂的化疗耐药性。
COMMD10, a member of COMMD protein, has been proved to target p65 NF-kappaB (nuclear factor-kappaB) subunit and reduce its nuclear translocation, thereby leading to the inactivation of NF-kappaB pathway and suppression of colorectal cancer invasion and metastasis. The aim of this study is to explore its expression pattern and tissue distribution in human normal tissues and other tumor tissues and to investigate the relevant mechanism. We firstly provided the expression profile and histological distribution of COMMD10 in various BALB/c mice tissues and identified the biological distribution of COMMD10 in different kinds of human normal and tumor tissues. We verified the expression profile of COMMD10 using TCGA database. The interacting genes of COMMD10 were predicted by using STRING using. Finally, we performed database, and the microRNAs targeting COMMD10 were predicted using miRDB, miRWalk, TargetScan and microRNA. GO and KEGG pathway analyses were performed to predict the biological function of COMMD10 and its interacting genes. mRNA expression of COMMD10 showed the highest level in the lung and spleen, and the lowest level in the heart and brain. Immunohistochemistry detection revealed that COMMD10 was expressed in different tissues with different degrees and was was located mainly in the cytoplasm. Subsequently, we showed that COMMD10 displayed various degrees of expression in different human normal tissues that mainly located in cytoplasm, while COMMD10 of liver cells resided in both nucleus and cytoplasm. All the tumor tissues except breast small cell carcinoma, breast phyllodes tumor, lung adenocarcinoma, thymoma, cervical cancer and bladder urothelial carcinoma showed that COMMD10 was positive staining in cytoplasm. Kaplan–Meier plotter indicated that renal clear cell carcinoma patients with increased expression level of COMMD10 exhibited longer survival. STRING database revealed that COMMD10 had 41 interacting genes, and data from 4 different databases indicated that hsa-miR-590-3p may be the potential regulator of COMMD10. GO analysis demonstrated that COMMD10 and its interacting genes were mainly enriched in Cullin-RING ubiquitin ligase complexes, binding and transport of copper ions, the transport and steady-state maintenance of copper ions, transcription, translation and transport of proteins, and negatively regulate the activity of NF-kappaB transcription factors. KEGG pathway showed that COMMD10 and its interacting genes were mainly involved in renal cell carcinoma, HIF-1 signaling pathways, ubiquitination-mediated proteolysis, endocytosis and mineral absorption. COMMD10 may play a tumor suppressive role in renal clear cell carcinoma through the miR-590-3p-COMMD10-Cul2-RBX1-NF-κB/HIF/NRF2 pathway and regulate the chemotherapy resistance of various tumor cells to cisplatin.