Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University,Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University,Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Oncol Rep. 2018 Dec;40(6):3171-3188. doi: 10.3892/or.2018.6766. Epub 2018 Oct 3.
The function of the expression of microRNA (miR)‑224‑5p in prostate adenocarcinoma (PCa) remains to be elucidated, therefore, the present study aimed to investigate the clinical significance and potential molecular mechanism of miR‑224‑5p in PCa. Data on the expression of miR‑224‑5p in PCa were extracted from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), ArrayExpress and previous literature, and meta‑analyses with standardized mean difference (SMD) and summary receiver operating characteristic (sROC) methods were performed for statistical analyses. The prospective target genes of miR‑224‑5p were collected by overlapping the differentially expressed mRNAs in TCGA and GEO, and target genes predicted by miRWalk2.0. Subsequently, in silico analysis was performed to examine the associated pathways of miR‑224‑5p in PCa. The expression of miR‑224‑5p was markedly lower in PCa; the overall SMD was ‑0.562, and overall sROC area under the curve was 0.80. In addition, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the prospective target genes of miR‑224‑5p were largely enriched in the amino sugar and nucleotide sugar metabolism signaling pathway, and three genes [UDP‑N‑acetylglucosamine pyrophosphorylase 1 (UAP1), hexokinase 2 (HK2) and chitinase 1 (CHIT1)] enriched in this pathway showed higher expression (P<0.05). In addition, key genes in the protein‑protein interaction network analysis [DNA topoisomerase 2‑α (TOP2A), ATP citrate lyase (ACLY) and ribonucleotide reductase regulatory subunit M2 (RRM2)] exhibited significantly increased expression (P<0.05). The results suggested that the downregulated expression of miR‑224‑5p may be associated with the clinical progression and prognosis of PCa. Furthermore, miR‑224‑5p likely exerts its effects by targeting genes, including UAP1, HK2, CHIT1, TOP2A, ACLY and RRM2. However, in vivo and in vitro experiments are required to confirm these findings.
微小 RNA（miR）-224-5p 在前列腺腺癌（PCa）中的表达功能尚不清楚，因此，本研究旨在探讨 miR-224-5p 在 PCa 中的临床意义和潜在分子机制。从癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）、ArrayExpress 和先前的文献中提取 miR-224-5p 在 PCa 中的表达数据，并采用标准化均数差（SMD）和综合受试者工作特征（sROC）方法进行荟萃分析进行统计分析。通过重叠 TCGA 和 GEO 中差异表达的 mRNAs 以及 miRWalk2.0 预测的靶基因，收集 miR-224-5p 的潜在靶基因。随后，通过京都基因与基因组百科全书分析（KEGG）对 miR-224-5p 在 PCa 中的相关通路进行了分析。结果显示，PCa 中 miR-224-5p 的表达明显降低；总 SMD 为-0.562，总 sROC 曲线下面积为 0.80。此外，KEGG 分析表明，miR-224-5p 的潜在靶基因主要富集在氨基糖和核苷酸糖代谢信号通路中，该通路中 3 个基因（UDP-N-乙酰氨基葡萄糖磷酸化酶 1（UAP1）、己糖激酶 2（HK2）和几丁质酶 1（CHIT1））表达上调（P<0.05）。此外，蛋白质-蛋白质相互作用网络分析中的关键基因[拓扑异构酶 2-α（TOP2A）、三磷酸柠檬酸裂解酶（ACLY）和核苷酸还原酶调节亚基 M2（RRM2）]表达显著增加（P<0.05）。这些结果表明，miR-224-5p 的下调表达可能与 PCa 的临床进展和预后有关。此外，miR-224-5p 可能通过靶向 UAP1、HK2、CHIT1、TOP2A、ACLY 和 RRM2 等基因发挥作用。然而，需要进行体内和体外实验来验证这些发现。
Zotero 插件
