Regulatory Network of MicroRNAs, Target Genes, Transcription Factors and Host Genes in Endometrial Cancer

Abstract

Genes and microRNAs (miRNAs) have important roles in human oncology. However, most of the biological factors are reported in disperse form which makes it hard to discover the pathology. In this study, genes and miRNAs involved in human endometrial cancer(EC) were collected and formed into regulatory networks following their interactive relations, including miRNAs targeting genes, transcription factors (TFs) regulating miRNAs and miRNAs included in their host genes. Networks are constructed hierarchically at three levels: differentially expressed, related and global. Among the three, the differentially expressed network is the most important and fundamental network that contains the key genes and miRNAs in EC. The target genes, TFs and miRNAs are differentially expressed in EC so that any mutation in them may impact on EC development. Some key pathways in networks were highlighted to analyze how they interactively influence other factors and carcinogenesis. Upstream and downstream pathways of the differentially expressed genes and miRNAs were compared and analyzed. The purpose of this study was to partially reveal the deep regulatory mechanisms in EC using a new method that combines comprehensive genes and miRNAs together with their relationships. It may contribute to cancer prevention and gene therapy of EC. The relations between miRNAs and target genes are studied. MiRNAs regulate a variety of cellular processes via the regulation of multiple target genes. They control the cellular expression machinery and have a profound impact on the regulation of signaling pathways (Lv et al., 2012).Host genes are genes where certain miRNAs locate. It is indicated that miRNAs are transcribed in parallel with their host transcripts and two different transcription classes of miRNAs, exonic and intronic, were identified (Rodriguez et al., 2004). Intronic miRNA and its host gene have a close relation (Baskerville et al., 2005).Numerous experimental data suggest that the differentially expressed genes and miRNAs contribute to the pathogenesis of EC, while related genes and miRNAs also play a part. However, the data can be found in scattered form, which makes it difficult to analyze the mechanism of EC systematically. In this study, genes and miRNAs are used to construct three networks including differentially expressed network, related network and global network. Each network is combined with three relationships of miRNAs targeting at genes, TFs regulating miRNAs and miRNAs locating on their host genes. Then contrast tables about upstream and downstream of genes and miRNAs are extracted to find the similarities and figure out differences. Crucial genes and miRNAs in the 476networks are focused on to reveal the pathogeneses of EC. Our teammates have successfully analyzed retinoblastoma using the same method . This study provides a new point of view to investigate EC.

The mechanism of miR-410-3p and miR-34c in nasopharyngeal carcinoma development and progression

“…Limited by the experimental level, the target of Mir-34c and Mir-410-3p on nasopharyngeal carcinoma cells has not yet been explored (42)(43)(44)(45)(46)(47). Therefore, further exploration and verification will be conducted in the future for the clinical use of Mir-34c and Mir-410-3p as markers of nasopharyngeal carcinoma.…”