基于ceRNA探讨白藜芦醇干预肾透明细胞癌的有效机制

目的 利用从肾透明细胞癌（ccRCC）数据集中筛选的差异表达基因、差异lncRNA及其上游miRNA,探索白藜芦醇可能的作用靶点,构建ccRCC的ceRNA网络。方法 从基因表达综合数据（GEO）及转录组数据库（TCGA）中检索并筛选ccRCC基因及lncRNA表达数据集,对差异表达基因（DEGs）进行富集和功能注释,使用在线数据库预测miRNA及长链非编码RNA（lncRNA）,通过加权基因共表达网络分析（WGCNA）鉴定该机制中可能的lncRNA,建立竞争性内源性RNA（ceRNAs）调控网络,并通过网络药理学分析确定白藜芦醇的药物靶点,探索白藜芦醇治疗ccRCC的分子作用机制。结果 构建了AL136040.1、SNHG17与上游hsa-miR-25-3p、hsa-miR-23a-3p及COL1A2、HRG的ceRNA调控网络,白藜芦醇与两个mRNA均显示良好的对接打分。结论 可能存在AL136040.1、SNHG17两个lncRNA与hsa-miR-25-3p、hsa-miR-23a-3p竞争性调控COL1A2、HRG,进一步影响ccRCC预后,可能是白藜芦醇治疗ccRCC的潜在机制。

Effective Mechanism of Resveratrol Intervention in Renal Clear Cell Carcinoma Based on ceRNA

Objective To explore the possible targets of resveratrol using differentially expressed genes, differential lncRNAs and their upstream miRNAs screened from the renal clear cell carcinoma (ccRCC) dataset to construct a ceRNA network for ccRCC.Methods The ccRCC gene and lncRNA expression datasets were retrieved and screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were enriched and functionally annotated, miRNAs and long-stranded non-coding RNAs (lncRNAs) were predicted using an online database, possible lncRNAs in this mechanism were identified by weighted gene co-expression network analysis (WGCNA), a regulatory network of competing endogenous RNAs (ceRNAs) was established, and the molecular mechanism of action of resveratrol for ccRCC was explored by identifying the drug targets of resveratrol through network pharmacology analysis.Results The ceRNA regulatory network of AL136040.1, SNHG17 with upstream hsa-miR-25-3p, hsa-miR-23a-3p and COL1A2, HRG was constructed, and resveratrol showed good docking scoring with both mRNAs.Conclusion There may exist two lncRNAs, AL136040.1 and SNHG17, competitively regulating COL1A2 and HRG with hsa-miR-25-3p and hsa-miR-23a-3p to further influence ccRCC prognosis, which may be a potential mechanism for resveratrol treatment of ccRCC.