An integrative bioinformatics analysis identified miR-375 as a candidate key regulator of malignant breast cancer
An integrative bioinformatics analysis identified miR-375 as a candidate key regulator of malignant breast cancer
复制标题
综合生物信息学分析确定 miR-375 是恶性乳腺癌的候选关键调节因子
DOI：
10.1007/s13353-019-00507-w
复制
发表时间：
2019-11-01
影响因子：
2.4
通讯作者：
Luo, Daya
中科院分区：
文献类型：
--
作者：
Liu, Jiaxuan;Wang, Ping;Luo, Daya
microRNAs（miRNAs）是在肿瘤发生过程中发挥重要生物学作用的关键调控因子，是肿瘤诊断和治疗的重要生物标志物。hsa-miR-375- 3 p（miR-375）在多种肿瘤类型中被认为是肿瘤抑制基因或癌基因，但其在恶性乳腺癌中的特异性表达和潜在调控作用尚不清楚。在这项研究中，来自非编码RNA微阵列分析的结果表明，与管腔样乳腺癌相比，miR-375在恶性基底样乳腺癌中的表达水平显著降低。在miR-375模拟转染的基底样乳腺癌细胞系中，共鉴定了1895个共下调和1645个共上调的基因。从在线数据库TargetScan和DIANA-microT-CDS获得预测的miR-375靶标。对共调节基因和预测的miR-375靶点的组合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，还表明了基底样乳腺癌中的特定调节通路，如RNA转运和加工。此外，进行基因表达微阵列分析伴随UALCAN分析以筛选基底样亚型中上调的基因。其中LDHB、CPNE 8、QKI和EIF 5A 2等4个潜在的关键基因被确定为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控因子，并为恶性乳腺癌的诊断和治疗发展提供了一个有前途的方向。
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, includingLDHB,CPNE8,QKI, andEIF5A2, 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.