Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: The results suggests that miR-223 and its targets, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3, might be reliable potential prognostic biomarkers in BRCA patients.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: The results suggests that miR-223 and its targets, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3, might be reliable potential prognostic biomarkers in BRCA patients.
摘要：
背景：乳腺癌（BRCA）是女性癌症相关死亡的最常见和主要原因。MicroRNAs（miRNA）是短的非编码RNA片段，在调节基因表达（包括癌症相关途径）中起作用。尽管在最近的研究中已经证明miR-223的失调在各种癌症中具有预后价值，其在BRCA中的诊断和预后作用尚不清楚.
方法：使用TCGA数据评估miR-223的表达和预后价值，并通过qRT-PCR验证。随后，通过使用三种不同的miRNA靶标预测工具和GEPIA数据库鉴定了miR-223的潜在致癌靶标。除了这些数据库，蛋白质-蛋白质相互作用网络，分子功能，预后价值，通过使用其他几种生物信息学工具和数据库，包括miR-223靶标的表达水平；例如，UALCAN,遗传和Metascape。
结果：生物信息学结果表明miR-223在BRCA中下调，并与患者的不良预后相关。体外实验证实miR-223在BRCA细胞中显著下调,MCF-7，SK-BR3，MDA-MB-231和HCC1500，与正常乳腺细胞系hTERT-HME1相比。此外，ANLN,DYNLT1、LRRC59、SLC12A8和TPM3基因基于其在BRCA中的表达和预后被鉴定为miR-223的潜在致癌靶基因。此外,这些靶基因的蛋白-蛋白相互作用网络主要富集在动力蛋白中间链结合,细胞分裂,细胞周期过程的调节，和细胞成分生物合成的正向调节。
结论：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。
方法：使用TCGA数据评估miR-223的表达和预后价值，并通过qRT-PCR验证。随后，通过使用三种不同的miRNA靶标预测工具和GEPIA数据库鉴定了miR-223的潜在致癌靶标。除了这些数据库，蛋白质-蛋白质相互作用网络，分子功能，预后价值，通过使用其他几种生物信息学工具和数据库，包括miR-223靶标的表达水平；例如，UALCAN,遗传和Metascape。
结果：生物信息学结果表明miR-223在BRCA中下调，并与患者的不良预后相关。体外实验证实miR-223在BRCA细胞中显著下调,MCF-7，SK-BR3，MDA-MB-231和HCC1500，与正常乳腺细胞系hTERT-HME1相比。此外，ANLN,DYNLT1、LRRC59、SLC12A8和TPM3基因基于其在BRCA中的表达和预后被鉴定为miR-223的潜在致癌靶基因。此外,这些靶基因的蛋白-蛋白相互作用网络主要富集在动力蛋白中间链结合,细胞分裂,细胞周期过程的调节，和细胞成分生物合成的正向调节。
结论：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。
