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利用生物信息学方法研究卡波西肉瘤中的关键微小RNA和靶标信使核糖核酸

Investigation of key miRNAs and Target-mRNA in Kaposi's sarcoma using bioinformatic methods.

作者信息

Wang Tianye, Zheng Jun, Pan Yangyang, Zhuang Zhaowei, Zeng Yan

机构信息

Precision Clinical Laboratory, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, Guangdong, China.

Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.

出版信息

Heliyon. 2024 Apr 16;10(8):e29502. doi: 10.1016/j.heliyon.2024.e29502. eCollection 2024 Apr 30.

Abstract

Kaposi's sarcoma (KS) is the second most common tumor in human immunodeficiency virus (HIV) infected patients worldwide. While many miRNAs have been confirmed to be involved in KS biological processes, no relevant studies have combined miRNA and mRNA expression profiles using KS patient tissue biopsies. In this study, we performed transcriptome sequencing on tumor and normal tissues from four KS patients and identified differentially expressed mRNA and miRNA, further performed target gene prediction and enrichment analysis. 19,551 target-mRNAs were identified by predicting 106 miRNAs, with 553 overlapping with 571 significantly differentially expressed mRNAs. Enrichment analysis showed significant involvement of the Ubiquitin-mediated proteolysis pathway. Additionally, the miRNA-mRNA interaction network was established, and the topological score of Cytohubba's algorithm was calculated for comparison with three other datasets. The Mutual Clustering Coefficient (MCC) scoring ranking placed ZBTB34, NFIB, and RORA as the top three mRNAs, while hsa-miR-16-5p, hsa-miR-27a-3p, hsa-miR-340-5p, hsa-miR-182-5p, and hsa-miR-186-5p ranked as the top five miRNAs. Hsa-miR-101-3p is the only miRNA that appears both in the top 10 MCC scores and at the intersection of the other two datasets. Finally, qRT-PCR was used to validate the findings at the cellular level. In summary, the miRNA analysis results indicated that hsa-miR-101-3p could be used as a potential diagnostic or therapeutic marker in future studies. Moreover, the mRNA analysis results suggested that the histone binding pathways involved in mRNAs and ubiquitin-related biological processes were closely associated with KS and could serve as promising biomarkers for the diagnosis and treatment of this disease.

摘要

卡波西肉瘤(KS)是全球感染人类免疫缺陷病毒(HIV)患者中第二常见的肿瘤。虽然许多微小RNA(miRNA)已被证实参与KS的生物学过程,但尚无相关研究使用KS患者组织活检将miRNA和信使核糖核酸(mRNA)表达谱结合起来。在本研究中,我们对4例KS患者的肿瘤组织和正常组织进行了转录组测序,鉴定出差异表达的mRNA和miRNA,进一步进行了靶基因预测和富集分析。通过预测106个miRNA鉴定出19,551个靶mRNA,其中553个与571个显著差异表达的mRNA重叠。富集分析表明泛素介导的蛋白水解途径显著参与其中。此外,建立了miRNA-mRNA相互作用网络,并计算了Cytohubba算法的拓扑分数以与其他三个数据集进行比较。相互聚类系数(MCC)评分排名中,锌指蛋白34(ZBTB34)、核纤维蛋白(NFIB)和维甲酸相关孤儿受体A(RORA)位列mRNA的前三名,而hsa-miR-16-5p、hsa-miR-27a-3p、hsa-miR-340-5p、hsa-miR-182-5p和hsa-miR-186-5p位列miRNA的前五名。Hsa-miR-101-3p是唯一同时出现在前10名MCC分数中以及其他两个数据集交集处的miRNA。最后,采用定量逆转录聚合酶链反应(qRT-PCR)在细胞水平验证了这些发现。总之,miRNA分析结果表明hsa-miR-101-3p在未来研究中可作为潜在的诊断或治疗标志物。此外,mRNA分析结果表明,mRNA中涉及的组蛋白结合途径和泛素相关生物学过程与KS密切相关,可作为该疾病诊断和治疗的有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/11041027/9054b5ce1143/gr1.jpg

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