Pan Wen-Ya, Zeng Jiang-Hui, Wen Dong-Yue, Wang Jie-Yu, Wang Peng-Peng, Chen Gang, Feng Zhen-Bo
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Oncol Lett. 2019 Feb;17(2):1695-1713. doi: 10.3892/ol.2018.9748. Epub 2018 Nov 22.
miR-15b-5p has frequently been reported to function as a biomarker in some malignancies; however, the function of miR-15b-5p in hepatocellular carcinoma (HCC) and its molecular mechanism are still not well understood. The present study was designed to confirm the clinical value of miR-15b-5p and further explore its underlying molecular mechanism. A comprehensive investigation of the clinical value of miR-15b-5p in HCC was investigated by data mining The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets as well as literature. In addition, intersected target genes of miR-15b-5p were predicted using the miRWalk database and differentially expressed genes of HCC from TCGA. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. Then, a protein-protein interaction network (PPI) was constructed to reveal the interactions between some hub target genes of miR-15b-5p. The miR-15b-5p expression level in HCC was predominantly overexpressed compared with non-HCC tissues samples (SMD=0.618, 95% CI: 0.207, 1.029; P<0.0001) based on 991 HCC and 456 adjacent non-HCC tissue samples. The pooled summary receiver operator characteristic (SROC) of miR-15b-5p was 0.81 (Q*=0.74), and the pooled sensitivity and specificity of miR-15b-5p in HCC were 72% (95% CI: 69-75%) and 68% (95% CI: 65-72%), respectively. Bioinformatically, 225 overlapping genes were selected as prospective target genes of miR-15b-5p in HCC, and profoundly enriched GO terms and KEGG pathway investigation in silico demonstrated that the target genes were associated with prostate cancer, proximal tubule bicarbonate reclamation, heart trabecula formation, extracellular space, and interleukin-1 receptor activity. Five genes (ACACB, RIPK4, MAP2K1, TLR4 and IGF1) were defined as hub genes from the PPI network. The high expression of miR-15b-5p could play an essential part in hepatocarcinogenesis through diverse regulation approaches.
miR-15b-5p常被报道在某些恶性肿瘤中作为生物标志物发挥作用；然而，miR-15b-5p在肝细胞癌（HCC）中的功能及其分子机制仍未完全明确。本研究旨在确认miR-15b-5p的临床价值，并进一步探究其潜在的分子机制。通过挖掘癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据集以及相关文献，对miR-15b-5p在HCC中的临床价值进行了全面调查。此外，利用miRWalk数据库和来自TCGA的HCC差异表达基因预测了miR-15b-5p的交集靶基因。进一步进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。然后，构建了蛋白质-蛋白质相互作用网络（PPI）以揭示miR-15b-5p的一些核心靶基因之间的相互作用。基于991例HCC组织样本和456例相邻非HCC组织样本，HCC中miR-15b-5p的表达水平与非HCC组织样本相比主要呈过表达（标准化均数差=0.618，95%置信区间：0.207，1.029；P<0.0001）。miR-15b-5p的汇总综合受试者工作特征曲线（SROC）为0.81（Q*=0.74），miR-15b-5p在HCC中的汇总敏感性和特异性分别为72%（95%置信区间：69-75%）和68%（95%置信区间：65-72%）。从生物信息学角度来看，225个重叠基因被选为HCC中miR-15b-5p的潜在靶基因，计算机模拟中深度富集的GO术语和KEGG通路研究表明，这些靶基因与前列腺癌肾小管近端碳酸氢盐重吸收、心脏小梁形成、细胞外空间和白细胞介素-1受体活性相关。五个基因（ACACB、RIPK4、MAP2K1、TLR4和IGF1）被定义为PPI网络中的核心基因。miR-15b-5p的高表达可能通过多种调控途径在肝癌发生过程中发挥重要作用。
