hsa-miR-22-3p和hsa-miR-671-5p靶标基因的预测及其与癌症患者生存率的相关性

Prediction of target genes has-miR-22-3p and has-miR-671-5p and their relationship to survival rate of patients with cancer

目的通过生物信息学方法预测在m6A去甲基化酶FTO敲低处理后,存在m6A修饰并显著下调的mi RNA(hsa-mi R-22-3p和hsa-mi R-671-5p)的靶标基因,并分析它们与癌症患者生存率的相关性。方法利用在线数据库寻找目标mi RNAs的靶基因,并通过基因功能(gene ontology,GO)和信号通路数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)对这些靶基因的分子功能(molecular function,MF)、生物过程(biological processes,BP)、细胞组分(cell component,CC)定位以及参与的信号通路进行分析;通过蛋白质互作网络(protein-protein interaction,PPI)筛选出核心基因,并分析它们与癌症患者生存率之间的相关性。结果 hsa-mi R-22-3p和hsa-mi R-671-5p共有198个相同的靶标基因;GO分析结果表明,这些靶基因在生物过程中显著丰富,包括肌动蛋白细胞骨架组织、神经元干细胞群维持、对尼古丁的行为反应;对于分子功能,这些靶点富含锌离子结合、蛋白质结构域特异性结合、核心启动子序列特异性DNA结合;细胞成分定位分析还显示,这些靶标在高尔基体的早期内体,细胞连接和整体成分中显著丰富;KEGG通路分析显示,这些交叉基因靶点在非小细胞肺癌、癌症中的胆碱代谢和粘蛋白型聚糖生物合成途径中富集;基于网络的工具分析显示,hsa-mi R-22-3p和hsa-mi R-671-5p已经它们的核心靶标基因RHOU和UNC5B与肾透明细胞癌(kidney renal clear cell carcinoma,KIRC)、肝癌(liver hepatocellular carcinoma,LIHC)、肺鳞状细胞癌(lung squamous cell carcinoma,LUSC)、低级胶质瘤(low-grade gliomas,LGG)、胃癌(stomach adenocarcinoma,STAD)、卵巢癌(ovarian serous cystadenocarcinoma,OV)、肉瘤(sarcoma,SARC)、膀胱癌(bladder urothelial carcinoma,BLCA)、皮肤癌(skin cutaneous melanoma,SKCM)、乳头状肾细胞癌(kidney renal papillary cell carcinoma,KIRP)和乳腺癌(breast invasive carcinoma,BRCA)等11种癌症有关。结论当去甲基化酶FTO被敲低或处于低活动水平时,一些mi RNA和基因可能在癌症中发挥不同的作用,也有可能成为治疗癌症的新的核酸靶点。

Objective To predict the two m6 A-modified mi RNAs（hsa-mi R-22-3 p and hsa-mi R-671-5 p） which were found to be significantly down-regulated in m6 A demethylase FTO knockdown cell lines by bioinformatics and investigate their relationship to the survival rate of patients with cancer. Methods The gene targets of these mi RNAs were searched by the online database,of which the molecular function（MF）,biological process（BP）,localization of cell components（CC）and signal pathway were analyzed by gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes（KEGG）databases. The hub genes were screened by protein-protein interaction（PPI）network and analyzed for the relationship to the survival rate of patients with cancer. Results A total of 198 intersectional gene targets were found in the two mi RNAs.GO analysis showed that these targets were significantly enriched in biological processes（BP）,including actin cytoskeleton organization,neuronal stem cell population maintenance and behavioral response to nicotine. For molecular function（MF）,these targets were enr iched in zinc ion binding,protein domain specific binding and core promoter sequencespecific DNA binding. In addition,GO cell component analysis also displayed that these targets were significantly enriched in the early endosome,cell junction,and integral component of Golgi membrane. KEGG pathway analysis showed that these intersectional gene targets were enriched in non-small cell lung cancer,choline metabolism in cancer and mucin type o-glycan biosynthesis. According to web-based tool oncolnc analysis,the two mi RNAs and top 2 hub genes RHOU and UNC5 B identified by PPI showed association with 11 kinds of cancers,i. e. kidney renal clear cell carcinoma（KIRC）,liver hepatocellular carcinoma（LIHC）,lung squamous cell carcinoma（LUSC）,low-grade gliomas（LGG）,stomach adeno-carcinoma（STAD）,ovarian serous cystadenocarcinoma（OV）,sarcoma（SARC）,bladder urothe-lial carcinoma（BLCA）,skin carcinoma（SKCM）,kidney renal papillary cell carcinoma（KIRP）and breast invasive carcinoma（BRCA）. Conclusion Some mi RNAs and genes might play different roles in cancer when the FTO has been knock down or at a low activity level,which are also possible to become a new nucleic acid targets for the treatment of cancer.