Identification of miRNA-mRNA associations in hepatocellular carcinoma using hierarchical integrative model

作者：Rency S. Varghese, Yuan Zhou, Megan E. Barefoot, Yifan Chen, Cristina Di Poto, Abdalla Kara Balla, Everett Oliver, Zaki A. Sherif, Deepak Kumar, Alexander Kroemer, Mahlet G. Tadesse, Habtom W. Ressom · 发表于：Research Square · 年份：2020 · DOI：10.21203/rs.2.16175/v4 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Cancer-related molecular mechanisms research

Abstract Background: The established role miRNA-mRNA regulation of gene expression has in oncogenesis highlights the importance of integrating miRNA with downstream mRNA targets. These findings call for investigations aimed at identifying disease-associated miRNA-mRNA pairs. Hierarchical integrative models (HIM) offer the opportunity to uncover the relationships between disease and the levels of different molecules measured in multiple omic studies. Methods: The HIM model we formulated for analysis of mRNA-seq and miRNA-seq data can be specified with two levels: (1) a mechanistic submodel relating mRNAs to miRNAs, and (2) a clinical submodel relating disease status to mRNA and miRNA, while accounting for the mechanistic relationships in the first level. Results: mRNA-seq and miRNA-seq data were acquired by analysis of tumor and normal liver tissues from 30 patients with hepatocellular carcinoma (HCC). We analyzed the data using HIM and identified 157 significant miRNA-mRNA pairs in HCC. The majority of these molecules have already been independently identified as being either diagnostic, prognostic, or therapeutic biomarker candidates for HCC. These pairs appear to be involved in processes contributing to the pathogenesis of HCC involving inflammation, regulation of cell cycle, apoptosis, and metabolism. For further evaluation of our method, we analyzed miRNA-seq and mRNA-seq data from TCGA network. While some of the miRNA-mRNA pairs we identified by analyzing both our and TC...