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分析 miR-497/195 簇鉴定宫颈癌的新治疗靶点。

Analysis of miR-497/195 cluster identifies new therapeutic targets in cervical cancer.

机构信息

Department of Molecular Biology, Yuvaraja's College, University of Mysore, Mysuru, Karnataka, 570005, India.

Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.

出版信息

BMC Res Notes. 2024 Aug 2;17(1):217. doi: 10.1186/s13104-024-06876-8.

DOI:10.1186/s13104-024-06876-8
PMID:39095857
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11297691/
Abstract

OBJECTIVE

miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets.

RESULTS

In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.

摘要

目的

miR-497/195 位于 17p13.1,是一个高度保守的 miRNA 簇,其异常表达是致癌作用的关键调节因子。我们使用公共数据集对 miR-497/195 簇进行了全面分析,以确定其在宫颈癌(CC)中的预后效用和作用。

结果

计算机分析和验证表明,该簇在 CC 中下调。总共鉴定出 miR-497/195 簇的 60 个靶基因在正常和 CC 样本之间表达差异。ShinyGO、STRING、CytoHubba、Timer 2.0、HPA 和 HCMBD 用于功能富集、PPIN 网络构建、枢纽基因鉴定、免疫浸润相关性、组织病理学表达以及 miR-497/195 簇及其靶基因的转移潜能的确定。PPIN 分析确定 CCNE1、CCNE2、ANLN、RACGAP1、KIF23、CHEK1、CDC25A、E2F7、CDK1 和 CEP55 为前 10 个枢纽基因(HGs)。此外,RECK、ATD5 和 BCL2 的上调以及 OSBPL3、RCAN3 和 HIST1H3H 的下调影响 CC 患者的总生存率。我们确定了 6 个 miR-497/195 簇的靶标(TFAP2A、CLSPN、RASEF、HIST1H3H、AKT3 和 ITPR1)来影响转移。此外,还确定了 8 个可药用基因和 38 种潜在药物。我们的研究确定了 miR-497/195 簇的靶基因和途径,可用于 CC 的预后和治疗应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/7e271b60441f/13104_2024_6876_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/3b1d6e7025a2/13104_2024_6876_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/87103015d9b1/13104_2024_6876_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/c783b9fcfdc6/13104_2024_6876_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/6e059d118638/13104_2024_6876_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/7e271b60441f/13104_2024_6876_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/3b1d6e7025a2/13104_2024_6876_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/87103015d9b1/13104_2024_6876_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/c783b9fcfdc6/13104_2024_6876_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/6e059d118638/13104_2024_6876_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f02/11297691/7e271b60441f/13104_2024_6876_Fig5_HTML.jpg

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