Regulatory network analysis of genes and microRNAs in human hepatoblastoma

Abstract

Hepatoblastoma (HB) is a common type of primary tumor in children. Previous studies have examined the expression of genes, including transcription factors (TFs), target genes, host genes and microRNAs (miRNAs or miRs) associated with HB. However, the regulatory pathways of miRNAs and genes remain unclear. In the present study, a novel perspective is proposed, which focuses on HB and the associated regulatory pathways, to construct three networks at various levels, including a differentially expressed network, an associated network and a global network. Genes and miRNAs are considered as key factors in the network. In the three networks, the associations between each pair of factors, including TFs that regulate miRNAs, miRNAs that interact with target genes and miRNAs that are located at host genes, were analyzed. The differentially expressed network is considered to be the most crucial of the three networks. All factors in the differentially expressed network were mutated or differentially expressed, which indicated that the majority of the factors were cancerogenic factors that may lead to HB. In addition, the network contained numerous abnormal linkages that may trigger HB. If the expression of each factor was corrected to a normal level, HB may be successfully treated. The associated network included more HB-associated genes and miRNAs, and was useful for analyzing the pathogenesis of HB. By analyzing these close associations, the first and the last factor of the regulatory pathways were revealed to have important roles in HB. For example, v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) was observed to regulateHomo sapiens (hsa)-miR-221, hsa-miR-18a and hsa-miR-17-5p, but no miRNAs targeted MYCN. In conclusion, the pathways and mechanisms underlying HB were expounded in the present study, which proposed a fundamental hypothesis for additional studies.