摘要
目的筛选结肠癌差异表达的lncRNA和miRNA,探讨其与结肠癌预后的关系及相关生物学功能。方法从TCGA数据库收集结肠癌患者的lncRNA和miRNA表达谱数据及临床资料,利用R软件筛选差异表达的lncRNA和miRNA;单因素Cox回归分析与预后显著相关的差异表达lncRNA和miRNA;miRNet数据库构建预后相关的lncRNA-miRNA网络,利用mirPath v.3软件对其进行功能富集分析;R软件构建预后风险模型并对其进行验证。采用CCK-8实验、划痕实验、流式细胞术及qPCR评估敲减TSPEAR-AS2对人结肠癌HCT116细胞增殖、迁移、凋亡及下游miRNA表达的影响。结果筛选出结肠癌组织中1823个差异表达的lncRNA和524个差异表达的miRNA;发现158个lncRNA和31个miRNA与结肠癌的预后相关;构建由8个lncRNA和14个miRNA组成的lncRNA-miRNA网络;GO和KEGG富集分析显示,lncRNA-miRNA网络主要参与肿瘤相关的生物学功能及通路;鉴定出11个能有效评价结肠癌预后特征的关键基因,由这11个关键基因构建的预后风险模型中高风险组生存时间显著短于低风险组(P<0.001),预测1、3和5年生存的AUC分别为0.70、0.74和0.71。敲减TSPEAR-AS2可抑制HCT116细胞增殖、迁移、促进细胞凋亡,并下调hsa-mir-4731-5p和hsa-mir-342-3p的表达。结论成功筛选结肠癌相关lncRNA-miRNA网络,并由此构建的预后风险模型具有良好的预测效能。TSPEAR-AS2参与调控结肠癌细胞的增殖、迁移、凋亡以及下游miRNA表达。
Objective To screen differentially expressed lncRNA and miRNA in colon cancer,and to explore their association with colon cancer prognosis and related biological functions.Methods The lncRNA and miRNA expression profile data and clinical information of colon cancer patients were collected from TCGA database,and R software was used to screen differentially expressed lncRNAs and miRNAs;Single-factor Cox regression analysis was used to identify differentially expressed lncRNA and miRNA that were significantly associated with prognosis;the miRNet database was used to construct a prognostic-related lncRNA-miRNA network;mirPath v.3 software was used for functional enrichment analysis;R software was used to build a prognostic risk model and validate it.CCK-8 experiments,scratch experiments,flow cytometry,and qPCR were used to evaluate the effects of knocking down TSPEAR-AS2 on the proliferation,migration,apoptosis and downstream miRNA expression of human colon cancer HCT116 cells.Results 1823 differentially expressed lncRNAs and 524 differentially expressed miRNAs were identified in colon cancer tissues;158 lncRNAs and 31 miRNAs were found to be associated with colon cancer prognosis;an lncRNA-miRNA network composed of 8 lncRNAs and 14 miRNAs was constructed;GO and KEGG enrichment analyses showed that the lncRNA-miRNA network was mainly involved in tumor-related biological functions and pathways;11 key genes that could effectively evaluate colon cancer prognostic characteristics were identified,the survival time of the high-risk group was significantly shorter than that of the low-risk group in the prognostic risk model constructed from these 11 key genes(P<0.001),and the AUCs for predicting the survival of 1,3,and 5 years were 0.70,0.74,and 0.71,respectively.Knocking down TSPEAR-AS2 inhibited the proliferation,migration,and promoted apoptosis of HCT116 cells,and down-regulated the expression of hsa-mir-4731-5p and hsa-mir-342-3p.Conclusion successful screening of colon cancer-associated lncRNA-miRNA network and the pro
作者
潘希望
邱模竞
郑林林
杨新博
徐晨
李太原
胡家萍
PAN Xi-wang;QIU Mo-jing;ZHENG Lin-lin;YANG Xin-bo;XU Chen;LI Tai-yuan;HU Jia-ping(Department of General Surgery,the First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,China)
出处
《南昌大学学报（医学版）》
2024年第1期6-13,共8页
Journal of Nanchang University：Medical Sciences
基金
江西省自然科学基金(20202BABL206802)。
