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通过生物信息学分析对去泛素化酶OTUD5作为宫颈癌生物标志物和治疗靶点的分析

Analysis of deubiquitinase OTUD5 as a biomarker and therapeutic target for cervical cancer by bioinformatic analysis.

作者信息

Bai Mixue, Che Yingying, Lu Kun, Fu Lin

机构信息

Institute of Chronic Disease, Qingdao University, Qingdao, Shandong, China.

出版信息

PeerJ. 2020 Jun 30;8:e9146. doi: 10.7717/peerj.9146. eCollection 2020.

Abstract

OTU deubiquitinase 5 (OTUD5), as a member of the ovarian tumor protease (OTU) family, was previously reported to play important roles in DNA repair and immunity. However, little is known about its function in tumors. Cervical cancer is a malignant tumor that seriously endangers the lives of women. Here, we found that low expression of OTUD5 in cervical cancer is associated with poor prognosis. Its expression is associated with tumor stage, metastatic nodes and tumor subtypes such as those related to the phosphatidylinositol-3-kinase (PI3K)-AKT signaling, epithelial-mesenchymal transition (EMT) and hormones. In addtion, we analyzed the coexpressed genes, related miRNAs, transcription factors, kinases, E3s and interacting proteins of OTUD5. We demonstrated that OTUD5 affects the expression levels of WD repeat domain 45 (WDR45), ubiquitin-specific peptidase 11 (USP11), GRIP1 associated protein 1 (GRIPAP1) and RNA binding motif protein 10 (RBM10). Moreover, hsa-mir-137, hsa-mir-1913, hsa-mir-937, hsa-mir-607, hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5. Furthermore, we performed enrichment analysis of 22 coexpressed genes, 33 related miRNAs and 30 interacting proteins. In addition to ubiquitination and immunology related processes, they also participate in Hippo signaling, insulin signaling, EMT, histone methylation and phosphorylation kinase binding. Our study for the first time analyzed the expression of OTUD5 in cervical cancer and its relationship with clinicopathology and provided new insights for further study of its regulatory mechanism in tumors.

摘要

卵巢肿瘤去泛素化酶5(OTUD5)作为卵巢肿瘤蛋白酶(OTU)家族的一员,先前有报道称其在DNA修复和免疫中发挥重要作用。然而,其在肿瘤中的功能却知之甚少。宫颈癌是一种严重危及女性生命的恶性肿瘤。在此,我们发现宫颈癌中OTUD5的低表达与预后不良相关。其表达与肿瘤分期、转移淋巴结以及肿瘤亚型有关,如与磷脂酰肌醇-3-激酶(PI3K)-AKT信号传导、上皮-间质转化(EMT)和激素相关的亚型。此外,我们分析了OTUD5的共表达基因、相关的微小RNA(miRNA)、转录因子、激酶、E3泛素连接酶和相互作用蛋白。我们证明OTUD5会影响WD重复结构域45(WDR45)、泛素特异性肽酶11(USP11)、GRIP1相关蛋白1(GRIPAP1)和RNA结合基序蛋白10(RBM10)的表达水平。此外,hsa-mir-137、hsa-mir-1913、hsa-mir-937、hsa-mir-607、hsa-mir-3149和hsa-mir-144可能会抑制OTUD5的表达。此外,我们对22个共表达基因、33个相关miRNA和30个相互作用蛋白进行了富集分析。除了泛素化和免疫相关过程外,它们还参与Hippo信号传导、胰岛素信号传导、EMT、组蛋白甲基化和磷酸化激酶结合。我们的研究首次分析了OTUD5在宫颈癌中的表达及其与临床病理的关系,并为进一步研究其在肿瘤中的调控机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f2/7333649/6af67474732c/peerj-08-9146-g001.jpg

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