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基于 RNA-seq 数据和实验的新型 miRNA 预测胆管癌的生存和预后。

Novel miRNA Predicts Survival and Prognosis of Cholangiocarcinoma Based on RNA-seq Data and Experiments.

机构信息

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China.

Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052 Henan, China.

出版信息

Biomed Res Int. 2020 Dec 9;2020:5976127. doi: 10.1155/2020/5976127. eCollection 2020.

Abstract

Accumulating evidence has demonstrated that microRNAs (miRNAs or miRs) play an important role in the diagnosis and prognosis of tumors. In the case of cholangiocarcinoma (CCA), miRNAs may serve as potential tumor biomarkers and therapeutic targets. Based on The Cancer Genome Atlas (TCGA) database, fold change >2 was used to screen out miRNAs with differential expression in patients with CCA. Univariate and multivariate Cox regression analyses identified miR-3913-5p as an independent prognostic factor in patients with CCA. Overall survival and progression-free survival of patients with CCA were analyzed based on clinical data from TCGA database. In addition, four datasets were combined to identify 21 possible target genes of miR-3913, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to predict potential pathways and functions of the molecular target genes. Subsequently, the miRNAs associated with survival were selected to build the miRNA-mRNA expression network. Furthermore, the differential expression of miR-3913-5p in CCA cells and normal bile duct epithelial cells was confirmed through experiments. The possible target genes (RNF24 and SIGLEC) were further screened by reverse transcription-quantitative PCR. In addition, functional experiments showed that miR-3913-5p might be an oncogene that affects the proliferation and migration of CCA cells by inhibiting and mimicking miR-3913-5p. Therefore, miR-3913 may serve as a biomarker for the diagnosis and prognosis of patients with CCA.

摘要

越来越多的证据表明,microRNAs(miRNAs 或 miRs)在肿瘤的诊断和预后中发挥着重要作用。在胆管癌(CCA)的情况下,miRNAs 可能作为潜在的肿瘤生物标志物和治疗靶点。基于癌症基因组图谱(TCGA)数据库,使用 fold change >2 筛选出 CCA 患者中差异表达的 miRNAs。单变量和多变量 Cox 回归分析确定 miR-3913-5p 是 CCA 患者的独立预后因素。根据 TCGA 数据库的临床数据分析 CCA 患者的总生存率和无进展生存率。此外,合并了四个数据集来鉴定 miR-3913 的 21 个可能的靶基因,并进行了基因本体论和京都基因与基因组百科全书分析,以预测分子靶基因的潜在途径和功能。随后,选择与生存相关的 miRNAs 构建 miRNA-mRNA 表达网络。此外,通过实验验证了 miR-3913-5p 在 CCA 细胞和正常胆管上皮细胞中的差异表达。通过逆转录定量 PCR 进一步筛选可能的靶基因(RNF24 和 SIGLEC)。此外,功能实验表明,miR-3913-5p 可能是一种通过抑制和模拟 miR-3913-5p 来影响 CCA 细胞增殖和迁移的癌基因。因此,miR-3913 可能作为 CCA 患者诊断和预后的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ee8/7787740/ddfa115bff0d/BMRI2020-5976127.002.jpg

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