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鸡与人类卵巢癌的比较转录组学研究。

Comparative transcriptomic study on the ovarian cancer between chicken and human.

机构信息

Key laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China; Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Sciences, Sichuan University, Chengdu, China.

Division of Vascular Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.

出版信息

Poult Sci. 2024 Sep;103(9):104021. doi: 10.1016/j.psj.2024.104021. Epub 2024 Jun 24.

Abstract

The laying hen is the spontaneous model of ovarian tumor. A comprehensive comparison based on RNA-seq from hens and women may shed light on the molecular mechanisms of ovarian cancer. We performed next-generation sequencing of microRNA and mRNA expression profiles in 9 chicken ovarian cancers and 4 normal ovaries, which has been deposited in GSE246604. Together with 6 public datasets (GSE21706, GSE40376, GSE18520, GSE27651, GSE66957, TCGA-OV), we conducted a comparative transcriptomics study between chicken and human. In the present study, miR-451, miR-2188-5p, and miR-10b-5p were differentially expressed in normal ovaries, early- and late-stage ovarian cancers. We also disclosed 499 up-regulated genes and 1,061 down-regulated genes in chicken ovarian cancer. The molecular signals from 9 cancer hallmarks, 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 369 Gene Ontology (GO) pathways exhibited abnormalities in ovarian cancer compared to normal ovaries via Gene Set Enrichment Analysis (GSEA). In the comparative analysis across species, we have uncovered the conservation of 5 KEGG and 76 GO pathways between chicken and human including the mismatch repair and ECM receptor interaction pathways. Moreover, a total of 174 genes contributed to the core enrichment for these KEGG and GO pathways were identified. Among these genes, the 22 genes were found to be associated with overall survival in patients with ovarian cancer. In general, we revealed the microRNA profiles of ovarian cancers in hens and updated the mRNA profiles previously derived from microarrays. And we also disclosed the molecular pathways and core genes of ovarian cancer shared between hens and women, which informs model animal studies and gene-targeted drug development.

摘要

产蛋鸡是卵巢肿瘤的自发模型。基于 RNA-seq 对鸡和女性的全面比较,可能会揭示卵巢癌的分子机制。我们对 9 例鸡卵巢癌和 4 例正常卵巢进行了 microRNA 和 mRNA 表达谱的下一代测序,这些数据已存入 GSE246604。结合 6 个公共数据集(GSE21706、GSE40376、GSE18520、GSE27651、GSE66957、TCGA-OV),我们对鸡和人之间的转录组进行了比较研究。在本研究中,miR-451、miR-2188-5p 和 miR-10b-5p 在正常卵巢、早期和晚期卵巢癌中表达不同。我们还揭示了鸡卵巢癌中 499 个上调基因和 1061 个下调基因。通过基因集富集分析(GSEA),9 个癌症标志、25 个京都基因与基因组百科全书(KEGG)途径和 369 个基因本体论(GO)途径的分子信号在卵巢癌中与正常卵巢相比表现异常。在跨物种的比较分析中,我们发现鸡和人类之间有 5 个 KEGG 和 76 个 GO 途径的保守性,包括错配修复和 ECM 受体相互作用途径。此外,还确定了 174 个基因对这些 KEGG 和 GO 途径的核心富集有贡献。在这些基因中,有 22 个基因与卵巢癌患者的总生存有关。总的来说,我们揭示了母鸡卵巢癌的 microRNA 谱,并更新了以前从微阵列中获得的 mRNA 谱。我们还揭示了母鸡和女性之间卵巢癌的分子途径和核心基因,这为模型动物研究和基因靶向药物开发提供了信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d86/11298922/f47e4c808acf/gr2.jpg

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