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通过生物信息学分析揭示miR-27b-3p作为马来女性乳腺癌潜在生物标志物的作用

Unraveling Roles of miR-27b-3p as a Potential Biomarker for Breast Cancer in Malay Women via Bioinformatics Analysis.

作者信息

Jusoh Ab Rashid, Al-Astani Bin Tengku Din Tengku Ahmad Damitri, Abdullah-Zawawi Muhammad-Redha, Abdul Rahman Wan Faiziah Wan, Nafi Siti Norasikin Mohd, Romli Roslaini Che, Hashim Ezzeddin Kamil Mohamed, Ab Patar Mohd Nor Azim, Yahya Maya Mazuwin

机构信息

Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.

Department of Biomedicine, School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia.

出版信息

Int J Mol Cell Med. 2023;12(3):257-274. doi: 10.22088/IJMCM.BUMS.12.3.257.

Abstract

Abnormal miRNA expression has been associated with breast cancer. Knowing miRNA and its target genes gives a better understanding of the biological mechanism behind the development of breast cancer. Here, we evaluated the potential prognostic and predictive values of miRNAs in breast cancer development by analyzing Malay women with breast cancer expression profiles. Seven differentially expressed miRNAs (DEMs) were subjected to miRNA‒target interaction network analysis (MTIN). A comprehensive MTIN was developed by integrating the information on miRNA and target gene interactions from five independent databases, including DIANA-TarBase, miRTarBase, miRNet, miRDB, and DIANA-microT. To understand the role of miRNAs in the progress of breast cancer, functional enrichment analysis of the miRNA target genes was conducted, followed by survival analysis to assess the prognostic values of the miRNAs and their target genes. In total, 1416 interactions were discovered among seven DEMs and 1274 target genes with a confidence score (CS) > 0.8. The overall survival analysis of the three most DEMs revealed a significant association of miR-27b-3p with poor prognosis in the TCGA breast cancer patient cohort. Further functional analysis of 606 miR-27b-3p target genes revealed their involvement in cancer-related processes and pathways, including the progesterone receptor signaling pathway, PI3K-Akt pathway, and EGFR transactivation. Notably, six high-confidence target genes (BTG2, DNAJC13, GRB2, GSK3B, KRAS, and UBR5) were discovered to be associated with worse overall survival in breast cancer patients, underscoring their essential roles in breast cancer development. Thus, we suggest that miR-27b-3p has significant potential as a biomarker for detecting breast cancer and can provide valuable understanding regarding the molecular mechanisms of the disease.

摘要

异常的miRNA表达与乳腺癌相关。了解miRNA及其靶基因有助于更好地理解乳腺癌发生背后的生物学机制。在此,我们通过分析患有乳腺癌的马来女性的表达谱,评估了miRNA在乳腺癌发生中的潜在预后和预测价值。对7个差异表达的miRNA(DEM)进行了miRNA-靶标相互作用网络分析(MTIN)。通过整合来自5个独立数据库(包括DIANA-TarBase、miRTarBase、miRNet、miRDB和DIANA-microT)的miRNA与靶基因相互作用信息,构建了一个全面的MTIN。为了了解miRNA在乳腺癌进展中的作用,对miRNA靶基因进行了功能富集分析,随后进行生存分析以评估miRNA及其靶基因的预后价值。在7个DEM和1274个靶基因之间共发现了1416个相互作用,置信度得分(CS)>0.8。对三个最显著的DEM进行的总生存分析显示,在TCGA乳腺癌患者队列中,miR-27b-3p与不良预后显著相关。对606个miR-27b-3p靶基因的进一步功能分析表明,它们参与了癌症相关的过程和途径,包括孕激素受体信号通路、PI3K-Akt通路和EGFR反式激活。值得注意的是,发现6个高置信度靶基因(BTG2、DNAJC13、GRB2、GSK3B、KRAS和UBR5)与乳腺癌患者较差的总生存相关,突出了它们在乳腺癌发生中的重要作用。因此,我们认为miR-27b-3p作为检测乳腺癌的生物标志物具有显著潜力,并可为该疾病的分子机制提供有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29fc/11092903/19d7dc87e3c5/ijmcm-12-257-g001.jpg

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