Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, People's Republic of China.
Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, People's Republic of China.
BMC Cancer. 2018 Jan 3;18(1):12. doi: 10.1186/s12885-017-3941-x.
Currently, some studies have demonstrated that miR-34a could serve as a suppressor of several cancers including hepatocellular carcinoma (HCC). Previously, we discovered that miR-34a was downregulated in HCC and involved in the tumorigenesis and progression of HCC; however, the mechanism remains unclear. The purpose of this study was to estimate the expression of miR-34a in HCC by applying the microarray profiles and analyzing the predicted targets of miR-34a and their related biological pathways of HCC.
Gene expression omnibus (GEO) datasets were conducted to identify the difference of miR-34a expression between HCC and corresponding normal tissues and to explore its relationship with HCC clinicopathologic features. The natural language processing (NLP), gene ontology (GO), pathway and network analyses were performed to analyze the genes associated with the carcinogenesis and progression of HCC and the targets of miR-34a predicted in silico. In addition, the integrative analysis was performed to explore the targets of miR-34a which were also relevant to HCC.
The analysis of GEO datasets demonstrated that miR-34a was downregulated in HCC tissues, and no heterogeneity was observed (Std. Mean Difference(SMD) = 0.63, 95% confidence intervals(95%CI):[0.38, 0.88], P < 0.00001; P = 0.08 I = 41%). However, no association was found between the expression value of miR-34a and any clinicopathologic characteristics. In the NLP analysis of HCC, we obtained 25 significant HCC-associated signaling pathways. Besides, we explored 1000 miR-34a-related genes and 5 significant signaling pathways in which CCND1 and Bcl-2 served as necessary hub genes. In the integrative analysis, we found 61 hub genes and 5 significant pathways, including cell cycle, cytokine-cytokine receptor interaction, notching pathway, p53 pathway and focal adhesion, which proposed the relevant functions of miR-34a in HCC.
Our results may lead researchers to understand the molecular mechanism of miR-34a in the diagnosis, prognosis and therapy of HCC. Therefore, the interaction between miR-34a and its targets may promise better prediction and treatment for HCC. And the experiments in vivo and vitro will be conducted by our group to identify the specific mechanism of miR-34a in the progress and deterioration of HCC.
目前，一些研究表明 miR-34a 可以作为包括肝细胞癌（HCC）在内的几种癌症的抑制剂。先前，我们发现 miR-34a 在 HCC 中下调，并参与 HCC 的发生和进展；然而，其机制尚不清楚。本研究旨在通过应用微阵列图谱来评估 HCC 中 miR-34a 的表达，并分析 miR-34a 的预测靶标及其与 HCC 相关的生物学途径。
通过基因表达综合 (GEO) 数据集来确定 HCC 与相应正常组织之间 miR-34a 表达的差异，并探讨其与 HCC 临床病理特征的关系。采用自然语言处理 (NLP)、基因本体论 (GO)、途径和网络分析来分析与 HCC 发生和进展相关的基因及其预测的 miR-34a 靶标。此外，还进行了综合分析，以探讨与 HCC 相关的 miR-34a 靶标。
GEO 数据集的分析表明，miR-34a 在 HCC 组织中下调，且无异质性（标准均数差 (SMD) = 0.63，95%置信区间 (95%CI)：[0.38, 0.88]，P < 0.00001；P = 0.08 I = 41%）。然而，miR-34a 的表达值与任何临床病理特征之间均无关联。在 HCC 的 NLP 分析中，我们获得了 25 个与 HCC 相关的显著信号通路。此外，我们还研究了 1000 个与 miR-34a 相关的基因和 5 个显著信号通路，其中 CCND1 和 Bcl-2 是必需的枢纽基因。在综合分析中，我们发现了 61 个枢纽基因和 5 个显著的通路，包括细胞周期、细胞因子-细胞因子受体相互作用、Notch 途径、p53 途径和焦点粘附，这表明 miR-34a 在 HCC 中的相关功能。
我们的结果可能使研究人员了解 miR-34a 在 HCC 的诊断、预后和治疗中的分子机制。因此，miR-34a 与其靶标的相互作用可能为 HCC 的预测和治疗提供更好的依据。我们小组将进行体内和体外实验，以确定 miR-34a 在 HCC 进展和恶化中的具体机制。
