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通过微阵列数据集的综合分析鉴定管腔型乳腺癌中的环状RNA-微小RNA-信使核糖核酸网络

Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets.

作者信息

Huang Yixiang, Qian Mingping, Chu Juhang, Chen Lei, Jian Wei, Wang Gang

机构信息

Department of Thyroid and Breast Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Front Mol Biosci. 2023 Apr 28;10:1162259. doi: 10.3389/fmolb.2023.1162259. eCollection 2023.

DOI:10.3389/fmolb.2023.1162259
PMID:37187897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10175596/
Abstract

Circular RNAs (circRNAs) regulatory network is important in human cancer. We, therefore, mapped the regulatory networks driven by circRNA in luminal-subtype breast cancer. Breast cancer-related microarray datasets from GEO database were analyzed for the differentially expressed circRNAs, miRNAs, and mRNAs. The potential downstream RNAs were collected using Circular RNA Interactome or Targetscan database. Protein-protein interaction (PPI) analysis was performed for the filtered genes to identify hub genes. The functions were annotated by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. CircRNA-miRNA-mRNA networks were mapped using Cytoscape software. Hsa_circ_0086735-miR-1296-5p-STAT1 axis was used for verification. The expression levels of hsa_circ_0086735, miR-1296-5p, and STAT1 mRNA were confirmed by qRT-PCR in luminal-subtype tissues and cell lines. The interactions among them were verified by Luciferase reporter assay and RNA pull-down assay. Cell proliferation and apoptosis were assayed. Overall and distant metastasis-free survival was analyzed. A total of 70 genes were finally targeted and enriched in multi-process and multi-pathway. Networks containing 96 circRNA-miRNA-mRNA axes were constructed. Hsa_circ_0086735 and STAT1 mRNA was upregulated in luminal breast cancer, while miR-1296-5p was downregulated. Hsa_circ_0086735-miR-1296-5p-STAT1 axis promotes breast cancer progression and contributes to tamoxifen resistance. High hsa_circ_0086735 was associated with poor overall and distant metastasis-free survival. This study identified the hsa_circ_0086735-miR-1296-5p-STAT1 as an important regulatory axis in luminal-subtype breast cancer, aiding to determine potential therapeutic targets.

摘要

环状RNA（circRNAs）调控网络在人类癌症中具有重要意义。因此，我们绘制了管腔亚型乳腺癌中由circRNA驱动的调控网络。对来自基因表达综合数据库（GEO数据库）的乳腺癌相关微阵列数据集进行分析，以找出差异表达的circRNAs、miRNAs和mRNAs。使用Circular RNA Interactome或Targetscan数据库收集潜在的下游RNA。对筛选出的基因进行蛋白质-蛋白质相互作用（PPI）分析，以识别枢纽基因。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析对功能进行注释。使用Cytoscape软件绘制circRNA-miRNA-mRNA网络。采用hsa_circ_0086735-miR-1296-5p-STAT1轴进行验证。通过qRT-PCR在管腔亚型组织和细胞系中确认hsa_circ_0086735、miR-1296-5p和STAT1 mRNA的表达水平。通过荧光素酶报告基因检测和RNA下拉检测验证它们之间的相互作用。检测细胞增殖和凋亡情况。分析总生存期和无远处转移生存期。最终共确定了70个基因，这些基因在多个过程和多条途径中富集。构建了包含96个circRNA-miRNA-mRNA轴的网络。hsa_circ_0086735和STAT1 mRNA在管腔型乳腺癌中上调，而miR-1296-5p下调。hsa_circ_0086735-miR-1296-5p-STAT1轴促进乳腺癌进展并导致他莫昔芬耐药。高表达的hsa_circ_0086735与较差的总生存期和无远处转移生存期相关。本研究确定hsa_circ_0086735-miR-1296-5p-STAT1是管腔亚型乳腺癌中的一个重要调控轴，有助于确定潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/52c7b88b9a00/fmolb-10-1162259-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/ca4cbc171c20/fmolb-10-1162259-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/47864b374523/fmolb-10-1162259-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/048a0dcc96bc/fmolb-10-1162259-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/69452b225fec/fmolb-10-1162259-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/b38c41e52514/fmolb-10-1162259-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/1a1a21de85c2/fmolb-10-1162259-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/d478a8d78f78/fmolb-10-1162259-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/52c7b88b9a00/fmolb-10-1162259-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/ca4cbc171c20/fmolb-10-1162259-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/47864b374523/fmolb-10-1162259-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/0a4ef2ab04a5/fmolb-10-1162259-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/048a0dcc96bc/fmolb-10-1162259-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/69452b225fec/fmolb-10-1162259-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/b38c41e52514/fmolb-10-1162259-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/1a1a21de85c2/fmolb-10-1162259-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/d478a8d78f78/fmolb-10-1162259-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fff/10175596/52c7b88b9a00/fmolb-10-1162259-g009.jpg

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