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整合竞争内源性 RNA 网络分析鉴定出新型 lncRNA 和基因参与转移性乳腺癌。

Integrative competing endogenous RNA network analyses identify novel lncRNA and genes implicated in metastatic breast cancer.

机构信息

Centre for Genomics and Personalised Health, School of Chemistry and Physics, Queensland University of Technology, 2 George Street, Brisbane, QLD, 4000, Australia.

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

出版信息

Sci Rep. 2023 Feb 10;13(1):2423. doi: 10.1038/s41598-023-29585-x.

Abstract

Competing endogenous RNAs (ceRNAs) have gained attention in cancer research owing to their involvement in microRNA-mediated gene regulation. Previous studies have identified ceRNA networks of individual cancers. Nevertheless, none of these studies has investigated different cancer stages. We identify stage-specific ceRNAs in breast cancer using the cancer genome atlas data. Moreover, we investigate the molecular functions and prognostic ability of ceRNAs involved in stage I-IV networks. We identified differentially expressed candidate ceRNAs using edgeR and limma R packages. A three-step analysis was used to identify statistically significant ceRNAs of each stage. Survival analysis and functional enrichment analysis were conducted to identify molecular functions and prognostic ability. We found five genes and one long non-coding RNA unique to the stage IV ceRNA network. These genes have been described in previous breast cancer studies. Genes acted as ceRNAs are enriched in cancer-associated pathways. Two, three, and three microRNAs from stages I, II, and III were prognostic from the Kaplan-Meier survival analysis. Our results reveal a set of unique ceRNAs in metastatic breast cancer. Further experimental work is required to evaluate their role in metastasis. Moreover, identifying stage-specific ceRNAs will improve the understanding of personalised therapeutics in breast cancer.

摘要

竞争内源性 RNA(ceRNA)在癌症研究中受到关注,因为它们参与了 microRNA 介导的基因调控。先前的研究已经确定了个别癌症的 ceRNA 网络。然而,这些研究中没有一个研究过不同的癌症阶段。我们使用癌症基因组图谱数据在乳腺癌中鉴定了特定于阶段的 ceRNA。此外,我们研究了参与 I-IV 期网络的 ceRNA 的分子功能和预后能力。我们使用 edgeR 和 limma R 包识别差异表达的候选 ceRNA。使用三步分析来识别每个阶段的统计学显著 ceRNA。进行生存分析和功能富集分析以识别分子功能和预后能力。我们发现了五个基因和一个长非编码 RNA 是 IV 期 ceRNA 网络所特有的。这些基因在以前的乳腺癌研究中已有描述。作为 ceRNA 的基因富集在癌症相关途径中。来自 I、II 和 III 期的两个、三个和三个 microRNA 来自 Kaplan-Meier 生存分析是预后的。我们的结果揭示了一组转移性乳腺癌中独特的 ceRNA。需要进一步的实验工作来评估它们在转移中的作用。此外,鉴定特定于阶段的 ceRNA 将提高对乳腺癌个体化治疗的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/596e/9918521/06b12fe951fa/41598_2023_29585_Fig1_HTML.jpg

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