Department of Nephrology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Exp Biol Med (Maywood). 2022 Aug;247(16):1466-1478. doi: 10.1177/15353702221104035. Epub 2022 Jun 25.
Chronic kidney disease (CKD) is a high mortality disease and generally remains asymptomatic in the early stages. Long non-coding RNA (lncRNA) is defined as a non-protein-coding transcript more than 200 nucleotides which participate in numerous biological processes and have been identified as novel diagnostic markers for many diseases. Detection of circulating lncRNAs is a rapidly evolving, new area of molecular diagnosis. The purpose of our research was to identify circulating lncRNA expression profiles and possible molecular mechanisms involved in CKD. Blood samples were obtained from patients with CKD and healthy volunteers, and high-throughput sequencing was performed to identify differentially expressed (DE) lncRNAs and mRNAs. DE lncRNAs and mRNAs in peripheral blood mononuclear cells (PBMCs) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to ensure the reliability and validity of RNA-seq data. Bioinformatics analysis was used to obtain biological functions and key pathways related to the pathogenesis of CKD. The interaction and co-expression functional networks for DE lncRNAs and mRNAs were also constructed. Our data showed that of the 425 DE lncRNAs detected, 196 lncRNAs were upregulated, while that of 229 lncRNAs were downregulated. A total of 433 DE mRNAs were identified in patients with CKD compared to healthy individuals. GO analysis revealed that DE lncRNAs were highly correlated with binding and pathway regulation. KEGG analysis suggested that DE lncRNAs were obviously enriched in regulatory pathways, such as antigen processing and presentation. We successfully constructed a potential DE lncRNA-mRNA co-expression network and analyzed the target genes of DE lncRNAs to predict cis- and trans-regulation in CKD. 100 lncRNAs that corresponded to 14 transcription factors (TFs) were identified in the TF-lncRNA binary network. Our findings on the lncRNA expression profiles and functional networks may help to interpret the possible molecular mechanisms implied in the pathogenesis of CKD; the results demonstrated that lncRNAs could potentially to be used as diagnostic biomarkers in CKD.
慢性肾脏病（CKD）是一种高死亡率疾病，在早期通常无症状。长链非编码 RNA（lncRNA）被定义为长度超过 200 个核苷酸的非蛋白编码转录本，参与许多生物过程，并已被确定为许多疾病的新型诊断标志物。循环 lncRNA 的检测是分子诊断的一个迅速发展的新领域。我们的研究目的是鉴定 CKD 相关的循环 lncRNA 表达谱和可能的分子机制。从 CKD 患者和健康志愿者中采集血液样本，并进行高通量测序以鉴定差异表达（DE）的 lncRNA 和 mRNA。通过定量逆转录聚合酶链反应（qRT-PCR）验证 PBMCs 中 DE lncRNA 和 mRNA 的表达，以确保 RNA-seq 数据的可靠性和有效性。利用生物信息学分析获得与 CKD 发病机制相关的生物学功能和关键途径。还构建了 DE lncRNA 和 mRNA 的相互作用和共表达功能网络。我们的数据显示，在检测到的 425 个 DE lncRNA 中，有 196 个 lncRNA 上调，而 229 个 lncRNA 下调。与健康个体相比，CKD 患者中共有 433 个 DE mRNA。GO 分析表明，DE lncRNA 与结合和途径调节高度相关。KEGG 分析表明，DE lncRNA 在调控途径中明显富集，如抗原加工和呈递。我们成功构建了一个潜在的 DE lncRNA-mRNA 共表达网络，并分析了 DE lncRNA 的靶基因，以预测 CKD 中的顺式和反式调控。在 TF-lncRNA 二值网络中，共鉴定出 100 个与 14 个转录因子（TF）相对应的 lncRNA。我们关于 lncRNA 表达谱和功能网络的研究结果可能有助于解释 CKD 发病机制中隐含的可能分子机制；结果表明，lncRNA 可能作为 CKD 的诊断生物标志物。
