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基于生物信息学的 miR-92a-3p 与他莫昔芬耐药乳腺癌细胞中关键基因相互作用分析。

Bioinformatics-based interaction analysis of miR-92a-3p and key genes in tamoxifen-resistant breast cancer cells.

机构信息

Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, 250012, PR China.

Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, 250012, PR China; Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, 250012, PR China.

出版信息

Biomed Pharmacother. 2018 Nov;107:117-128. doi: 10.1016/j.biopha.2018.07.158. Epub 2018 Aug 4.

DOI:10.1016/j.biopha.2018.07.158
PMID:30086458
Abstract

The abnormal expression of miR-92a-3p was detected in multiple cancers. However, the biological role and underlying mechanism of miR-92a-3p in tamoxifen-resistant cells are still unknown. The main objective of our study was to find potential miR-92a-3p regulating pathways involved in tamoxifen resistance and to construct their regulatory network using bioinformatics. Four gene expression profiles were retrieved from GEO database and the GEO2R tool was used for analysis. GSE41922 and GSE42072 were applied to investigate aberrant miR-92a-3p expression in breast cancer serum and tissue. We found that miR-92a-3p expression was higher in breast cancer serum or tissue than in healthy volunteer serum or adjacent normal tissue, and high expression of miR-92a-3p could predict poor prognosis of breast cancer patients. In our qRT-PCR validation, we found that miR-92a-3p was upregulated in tamoxifen-resistant cells. MiR-92a-3p might play a role in tamoxifen resistance. In order to find the relationship between miR-92a-3p and some key genes and their potential molecular mechanisms in tamoxifen-resistant cells. The microarray data GSE26459 and GSE28267 were analyzed to determine the differentially expressed genes (DEGs) or miRNAs (DEMs). Furthermore, the related long non-coding RNAs (lncRNAs) were screened with starBase v2.0. Finally,microRNA.org,miRDB, targetminer and targetscan were applied to predict the targets of miR-92a-3p. Through analysis, we find that miR-92a-3p may be used as a potential biomarker for early detection of cancer and monitoring the efficacy of endocrine therapy.

摘要

miR-92a-3p 的异常表达在多种癌症中被检测到。然而,miR-92a-3p 在他莫昔芬耐药细胞中的生物学作用和潜在机制尚不清楚。本研究的主要目的是寻找潜在的 miR-92a-3p 调节途径,参与他莫昔芬耐药,并使用生物信息学构建它们的调节网络。从 GEO 数据库中检索了四个基因表达谱,并使用 GEO2R 工具进行分析。GSE41922 和 GSE42072 用于研究乳腺癌血清和组织中异常的 miR-92a-3p 表达。我们发现,miR-92a-3p 在乳腺癌血清或组织中的表达高于健康志愿者血清或相邻正常组织,并且 miR-92a-3p 的高表达可以预测乳腺癌患者的不良预后。在我们的 qRT-PCR 验证中,我们发现 miR-92a-3p 在他莫昔芬耐药细胞中上调。miR-92a-3p 可能在他莫昔芬耐药中发挥作用。为了寻找 miR-92a-3p 与一些关键基因之间的关系及其在他莫昔芬耐药细胞中的潜在分子机制。对微阵列数据 GSE26459 和 GSE28267 进行了分析,以确定差异表达基因 (DEGs) 或 microRNAs (DEMs)。此外,利用 starBase v2.0 筛选相关的长链非编码 RNA (lncRNAs)。最后,应用 microRNA.org、miRDB、targetminer 和 targetscan 预测 miR-92a-3p 的靶标。通过分析,我们发现 miR-92a-3p 可能作为癌症早期检测和监测内分泌治疗效果的潜在生物标志物。

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