Analysis of microarrays of miR-34a and its identification of prospective target gene signature in hepatocellular carcinoma

Abstract

Background: 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. Methods: 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. Results: 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; Pheterogeneity = 0.08 I2 = 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. Conclusion: 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.