miR-223在乳腺癌中的作用;综合分析。
The role of miR-223 in breast cancer; an integrated analysis.
发表日期:2023 Nov 04
作者:
Yunus Sahin, Zekiye Altan, Aydın Karabulut, Khandakar A S M Saadat, Ahmet Arslan
来源:
Cell Death & Disease
摘要:
乳腺癌(BRCA)是女性癌症相关死亡的最常见和主要原因。 MicroRNA (miRNA) 是短的非编码 RNA 片段,在调节基因表达(包括癌症相关通路)中发挥作用。尽管最近的研究已证明miR-223的失调在多种癌症中具有预后价值,但其在BRCA中的诊断和预后作用仍不清楚。使用TCGA数据评估miR-223的表达和预后价值,并通过qRT进行验证-PCR。随后,通过使用三种不同的 miRNA 靶点预测工具和 GEPIA 数据库,鉴定了 miR-223 的潜在致癌靶点。除了这些数据库之外,还使用其他几种生物信息学工具和数据库包括了蛋白质-蛋白质相互作用网络、分子功能、预后价值和 miR-223 靶标的表达水平;生物信息学结果表明,miR-223在BRCA中表达下调,并与患者不良预后相关。体外实验证实,与正常乳腺细胞系 hTERT-HME1 相比,miR-223 在 BRCA 细胞、MCF-7、SK-BR3、MDA-MB-231 和 HCC1500 中显着下调。此外,根据 ANLN、DYNLT1、LRRC59、SLC12A8 和 TPM3 基因在 BRCA 中的表达和预后,这些基因被确定为 miR-223 的潜在致癌靶基因。此外,这些靶基因的蛋白质-蛋白质相互作用网络主要富集于动力蛋白中间链结合、细胞分裂、细胞周期过程的调节以及细胞成分生物合成的正向调节。结果表明,miR-223及其靶标ANLN、 DYNLT1、LRRC59、SLC12A8 和 TPM3 可能是 BRCA 患者可靠的潜在预后生物标志物。© 2023。作者获得 Springer Nature B.V. 的独家许可。
Breast cancer (BRCA) is the most common and leading cause of cancer-related death in women. MicroRNAs (miRNAs) are short non-coding RNA fragments that play a role in regulating gene expression including the cancer-related pathways. Although dysregulation of miR-223 has been demonstrated in recent studies to have prognostic value in various cancers, its diagnostic and prognostic role in BRCA remains unknown.The expression and the prognostic value of miR-223 were evaluated using the TCGA data and verified by qRT-PCR. Subsequently, potential oncogenic targets of miR-223 were identified by using three different miRNA target prediction tools and the GEPIA database. In addition to these databases, protein-protein interaction network, molecular functions, prognostic value, and the expression level of miR-223 targets were included by using several other bioinformatics tools and databases; such as, UALCAN, GeneMANIA and Metascape.The bioinformatic results demonstrated that miR-223 downregulated in BRCA and associated with poor prognosis of patients. In vitro experiments validated that miR-223 significantly downregulated in BRCA cells, MCF-7, SK-BR3, MDA-MB-231 and HCC1500, compared to normal breast cell line hTERT-HME1. Furthermore, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3 genes were identified as the potential oncogenic target genes of miR-223 based on their expression and prognosis in BRCA. Additionally, protein-protein interaction network of these target genes was mainly enriched in dynein intermediate chain binding, cell division, regulation of cell cycle process, and positive regulation of cellular component biogenesis.The results suggests that miR-223 and its targets, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3, might be reliable potential prognostic biomarkers in BRCA patients.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.