Queen Mary School, Nanchang University, Nanchang, 330006, Jiangxi, China.
Department of Pathology, The Affiliated Infectious Diseases Hospital, Nanchang University, Nanchang, 330002, Jiangxi, China.
J Appl Genet. 2019 Nov;60(3-4):335-346. doi: 10.1007/s13353-019-00507-w. Epub 2019 Aug 1.
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.
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。