Exploration of the pathways and interaction network involved in bladder cancer cell line with knockdown of Opa interacting protein 5
Exploration of the pathways and interaction network involved in bladder cancer cell line with knockdown of Opa interacting protein 5
复制标题
通过敲低 Opa 相互作用蛋白 5 探索膀胱癌细胞系中涉及的通路和相互作用网络
DOI：
10.1016/j.prp.2017.07.029
复制
发表时间：
2017-01-01
影响因子：
2.8
通讯作者：
He, Jun
中科院分区：
文献类型：
--
作者：
He, Xuefeng;Ding, Xiang;He, Jun
目的：我们在前期的研究中发现，敲低Opa相互作用蛋白5（OIP 5）可抑制膀胱癌细胞的生长，扰乱细胞周期，增加细胞凋亡。本研究旨在探讨OIP 5在BC中作用的潜在途径和相互作用网络。方法：采用基因芯片技术分析OIP 5敲低（shOIP 5）和对照（shCtrl）BC细胞系的mRNA表达谱。进行生物信息学分析，包括差异表达mRNA（DEGs）的鉴定、蛋白质相互作用网络的构建、生物学功能的预测和独创性通路分析（IPA）。结果：与shCtrl组相比，shOIP 5组分别有255个和184个DEG表达上调和下调。在PPI网络中，CANDI和MYC与DEG的连通性最高。439个DEG在炎症反应、细胞增殖调节、Toll样受体信号通路、酪氨酸-胞苷受体相互作用和膀胱癌中显著富集。在疾病和功能富集中，DEGs明显参与细胞运动、细胞生长和增殖、癌变、炎症反应、细胞死亡和存活。在OIP 5调控网络中，CDH 2、IRS 1、IRAK 3、ID 1、TNF、IL 6、ITGA 6、MYC和SOD 2与OIP 5相互作用。WB验证结果与我们的生物信息学分析结果一致。结论：OIP 5相互作用网络可能作为癌基因在基于异常炎症反应的BC进展中发挥作用。本研究为探讨乳腺癌的发生机制提供了有价值的信息。
Objectives: In our previous study, we displayed that knockdown of Opa interacting protein 5 (OIP5) inhibited cell growth, disturbed cell cycle and increased cell apoptosis in bladder cancer (BC) cell line. Our present study aimed to explore the underlying pathways and interaction network involved in the roles of OIP5 in BC.Methods: Microarray analysis was conducted to obtain mRNA expression profiling of OIP5 knockdown (shOIP5) and control (shCtrl) BC cell lines. Bioinformatics analyses were performed including differentially expressed mRNAs (DEGs) identification, protein-protein interaction network construction, biological functions of prediction and ingenuity pathways analysis (IPA). Western Blotting (WB) was subjected to validate the protein expression levels of candidate DEGs in shOIP5 BC cell line.Results: Respective 255 up- and 184 down-regulated DEGs were identified in shOIP5 group compared with shCtrl group. In the PPI network, CANDI and MYC had the highest connectivity with DEGs. 439 DEGs were significantly enriched in inflammatory response, regulation of cell proliferation, Toll-like receptor signaling pathway, cytokine-cytoldne receptor interaction and bladder cancer. In the disease and function enrichment, DEGs were obviously involved in cellular movement, cellular growth and proliferation, cancer, inflammatory response, cell death and survival. In the OIP5 regulatory network, CDH2, IRS1, IRAK3, ID1, TNF, IL6, ITGA6, MYC and SOD2 interacted with OIP5. The WB validation results were compatible with our bioinformatics analyses.Conclusions: OIP5 interaction network might function as an oncogene in BC progression based on aberrant inflammatory responses. Our study might provide valuable information for investigation of tumorigenesis mechanism in BC.