研究动态
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通过体外和体内方法,基因组学和转录组学分析了与乳腺癌调节关联的miRNA和mRNA的差异表达。

Identification of differentially expressed miRNAs and mRNAs associated with the regulation of breast cancer via in silico and in vitro methods.

发表日期:2023 Oct
作者: Pelin Telkoparan-Akillilar, Dilek Cevik
来源: GENES & DEVELOPMENT

摘要:

BC发展过程中,miRNA的表达发生改变。本研究的目的是鉴定与癌症相关的新miRNAs和通路,以了解BC亚型的机制。从基因表达纲目数据库(GEO)中下载了GSE59247数据集,并使用GEO2R软件进行了分析。通过miRNome PCR阵列评估了BC细胞中差异miRNA的表达。采用Venn图揭示GSE59247数据集和miRNome阵列之间的共同差异表达的miRNAs。通过Kaplan-Meier曲线评估所选miRNAs的临床预后意义。进行KEGG通路富集分析,以找到miRNA靶点,结果通过TNM图分析和q-RT-PCR进行验证。使用TargetScan数据库预测miRNAs与靶基因3'-非翻译区的关联,并使用人类蛋白质图谱数据库可视化其表达。Venn图分析显示了基于计算和基于体外实验的11个miRNAs的重叠。KEGG分析显示“赖氨酸降解通路”是最显著富集的靶向通路。q-RT-PCR结果证实,赖氨酸降解通路相关基因SETD7、SETDB2、EHHADH、SETMAR、KMT2A和SUV39H2在BC细胞中表达差异。靶位预测分析确定miR-1323-5p与SETD7的3'-UTR、miR-129-5p与EHHADH的3'-UTR、miR-628-5p与SETDB2的3'-UTR的结合位点。值得注意的是,miR-1323-5p、miR-129-5p和miR-628-5p在BC中表达差异,并结合了赖氨酸降解通路的关键基因SETD7、SETDB2和EHHADH的3'UTR。这些miRNAs可能作为BC进展的潜在诊断和预后生物标志物。[版权信息] © The Author(s),独家授权给Springer Nature B.V. 2023。Springer Nature或其许可方(例如协会或其他合作伙伴)根据与作者或其他权利持有人的出版协议完全拥有本文章的专有权利;文章的接受稿版本的作者自行存档仅受此类出版协议和适用法律的约束。
miRNA expressions are altered during development of breast cancer (BC). The aim of this study is to identify novel cancer-related miRNAs and pathways to understand the mechanisms of BC subtypes. GSE59247 dataset was downloaded from gene expression omnibus (GEO) database and analyzed with GEO2R software. The differential miRNA expressions in BC cells were evaluated by miRNome PCR array. Venn diagram was used to reveal co-differentially expressed miRNAs between GSE59247 dataset and miRNome array. Clinical prognostic significance of selected miRNAs was evaluated via Kaplan Meier curve. KEGG pathway enrichment analysis was performed to find miRNA targets and results were validated by TNM plot analysis and q-RT-PCR. TargetScan database was used to predict the association of miRNAs and 3'-untranslated regions of target genes and their expressions were visualized by human protein atlas database. Venn diagram analysis showed overlap of 11 miRNAs from in silico and in vitro analysis. KEGG analysis revealed 'Lysine Degradation Pathway' as the most significantly enriched targeted pathway. q-RT-PCR results confirmed that Lysine degradation pathway related genes SETD7, SETDB2, EHHADH, SETMAR, KMT2A and SUV39H2 were differentially expressed in BC cells. Target prediction analysis identified binding sites between miR-1323-5p and 3'-UTR of SETD7, miR-129-5p and 3'-UTR of EHHADH and miR-628-5p and 3'-UTR of SETDB2 mRNA. Notably, miR-1323-5p, miR-129-5p, and miR-628-5p are differentially expressed in BC and they bind to 3'UTR of critical genes of Lysine degradation pathway, namely SETD7, SETDB2 and EHHADH. These miRNAs might serve as potential diagnostic and prognostic biomarkers for progression.© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.