Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Reprod Biol. 2021 Mar;21(1):100482. doi: 10.1016/j.repbio.2021.100482. Epub 2021 Feb 3.
The miR-15a/16-1 cluster is abnormally expressed in cervical cancer (CC) tissues and plays a vital role in cervical carcinogenesis. We aimed to evaluate the miR-15a/16-1 expression in healthy and cancerous cervical tissues, identify the associated networks, and to test its prognostic significance. miR-15a/16-1-MC expressions were analyzed in TCGA-CESC datasets by UALCAN, GEPIA2, and Datasetviewer. miR-15a/16-1 validated targets were extracted from mirTarBase and in silico functional analysis of the target genes were performed using WebGestalt. The interaction networks were constructed by the miRNet, STRING, and NetworkAnalyst tools. The prognostic significance and metastatic potential of the target genes were predicted using UALCAN and HCMDB. The FDA approved drugs to target miR-15a/16-1 and target gene network in CC were performed using DGIdb, STITCH and PanDrugs. TCGA-CESC and GEO data analysis suggested significant overexpression of miR-15a/16-1 in CC samples. The Kaplan-Meier survival analysis showed that miR-15a and its four target genes (BCL2, CCNE1, NUP50, and RBPJ) influence the overall survival of CC patients. Among the 66 differentially expressed target genes, 12 of them are linked to head, neck, or lung metastasis. Functional enrichment analysis predicted the association of this cluster with p53 signaling, human papillomavirus infection, PI3-AKT signaling pathway, and pathways in cancer. Drug-gene interaction analysis showed 52 potential FDA approved drugs to interact with the miR-15a/16-1 target genes. Nine of the 52 drugs are currently used as a chemotherapeutic agent for the treatment of CC patients. The present study shows that miR-15a/16-1 expression can be used as a clinical marker and target for therapy in CC.
miR-15a/16-1 簇在宫颈癌 (CC) 组织中异常表达，在宫颈癌的发生中起着至关重要的作用。本研究旨在评估 miR-15a/16-1 在健康和癌变宫颈组织中的表达，鉴定相关网络，并检验其预后意义。通过 UALCAN、GEPIA2 和 Datasetviewer 分析 TCGA-CEC 数据集的 miR-15a/16-1-MC 表达。从 mirTarBase 中提取 miR-15a/16-1 的验证靶标，并使用 WebGestalt 对靶基因进行功能分析。通过 miRNet、STRING 和 NetworkAnalyst 工具构建互作网络。使用 UALCAN 和 HCMDB 预测靶基因的预后意义和转移潜能。使用 DGIdb、STITCH 和 PanDrugs 分析 FDA 批准用于靶向 miR-15a/16-1 和靶基因网络的药物。TCGA-CEC 和 GEO 数据分析表明，CC 样本中 miR-15a/16-1 表达显著上调。Kaplan-Meier 生存分析表明，miR-15a 及其四个靶基因（BCL2、CCNE1、NUP50 和 RBPJ）影响 CC 患者的总生存率。在 66 个差异表达的靶基因中，有 12 个与头颈部或肺部转移有关。功能富集分析预测该簇与 p53 信号、人乳头瘤病毒感染、PI3-AKT 信号通路和癌症途径有关。药物-基因相互作用分析显示，有 52 种潜在的 FDA 批准药物与 miR-15a/16-1 靶基因相互作用。这 52 种药物中有 9 种目前被用作治疗 CC 患者的化疗药物。本研究表明，miR-15a/16-1 的表达可以作为 CC 的临床标志物和治疗靶点。
