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一项综合生物信息学分析鉴定 miR-375 为恶性乳腺癌的候选关键调控因子。

An integrative bioinformatics analysis identified miR-375 as a candidate key regulator of malignant breast cancer.

机构信息

Queen Mary School, Nanchang University, Nanchang, 330006, Jiangxi, China.

Department of Pathology, The Affiliated Infectious Diseases Hospital, Nanchang University, Nanchang, 330002, Jiangxi, China.

出版信息

J Appl Genet. 2019 Nov;60(3-4):335-346. doi: 10.1007/s13353-019-00507-w. Epub 2019 Aug 1.

DOI:10.1007/s13353-019-00507-w
PMID:31372832
Abstract

MicroRNAs (miRNAs) are key regulators that play important biological roles in carcinogenesis and are promising biomarkers for cancer diagnosis and therapy. hsa-miR-375-3p (miR-375) has been suggested to serve as a tumor suppressor or oncogene in various tumor types; however, its specific expression and potential regulatory role in malignant breast cancer remain unclear. In this study, the results from noncoding RNA microarray analysis indicated that the miR-375 expression level is significantly decreased in malignant basal-like breast cancer compared with luminal-like breast cancer. A total of 1895 co-downregulated and 1645 co-upregulated genes were identified in miR-375 mimic-transfected basal-like breast cancer cell lines. Predicted miR-375 targets were obtained from the online databases TargetScan and DIANA-microT-CDS. Combined KEGG enrichment analysis for coregulated genes and predicted miR-375 targets provided information and revealed differences in potential dynamic signaling pathways regulated by miR-375 and also indicated specific regulatory pathways, such as RNA transport and processing, in basal-like breast cancer. Additionally, gene expression microarray analysis accompanied by UALCAN analysis was performed to screen upregulated genes in the basal-like subtype. Four potential key genes, including LDHB, CPNE8, QKI, and EIF5A2, were identified as candidate target genes of miR-375. Therefore, the present study demonstrated that miR-375 may be a potential key regulator and provide a promising direction for diagnostic and therapeutic developments for malignant breast cancer.

摘要

微小 RNA(miRNA)是关键的调控因子,在致癌作用中发挥着重要的生物学作用,是癌症诊断和治疗有前途的生物标志物。hsa-miR-375-3p(miR-375)已被认为在各种肿瘤类型中作为肿瘤抑制因子或癌基因发挥作用;然而,其在恶性乳腺癌中的具体表达和潜在调节作用尚不清楚。在这项研究中,非编码 RNA 微阵列分析的结果表明,miR-375 的表达水平在恶性基底样乳腺癌中明显低于腔样乳腺癌。在 miR-375 模拟转染的基底样乳腺癌细胞系中,共鉴定到 1895 个下调和 1645 个上调的基因。从在线数据库 TargetScan 和 DIANA-microT-CDS 获得预测的 miR-375 靶基因。对核心调控基因和预测的 miR-375 靶基因进行联合 KEGG 富集分析,提供了信息并揭示了 miR-375 调节的潜在动态信号通路的差异,也表明了特定的调节通路,如 RNA 运输和加工,在基底样乳腺癌中。此外,还进行了基因表达微阵列分析并结合 UALCAN 分析,以筛选基底样亚型中上调的基因。鉴定到四个潜在的关键基因,包括 LDHB、CPNE8、QKI 和 EIF5A2,作为 miR-375 的候选靶基因。因此,本研究表明 miR-375 可能是一个潜在的关键调节因子,并为恶性乳腺癌的诊断和治疗发展提供了有前途的方向。

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