Abstract
Aim: we aimed to construct a bioinformatics-based co-regulatory network of mRNAs and non coding RNAs (ncRNAs), which is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), followed by its validation in a NAFLD animal model. Materials and Methods: The mRNAs–miRNAs–lncRNAs regulatory network involved in NAFLD was retrieved and constructed utilizing bioinformatics tools. Then, we validated this network using an NAFLD animal model, high sucrose and high fat diet (HSHF)-fed rats. Finally, the expression level of the network players was assessed in the liver tissues using reverse transcriptase real-time polymerase chain reaction. Results: in-silico constructed network revealed six mRNAs (YAP1, FOXA2, AMOTL2, TEAD2, SMAD4 and NF2), two miRNAs (miR-650 and miR-1205), and two lncRNAs (RPARP-AS1 and SRD5A3-AS1) that play important roles as a co-regulatory network in NAFLD pathogenesis. Moreover, the expression level of these constructed network–players was significantly different between NAFLD and normal control. Conclusion and future perspectives: this study provides new insight into the molecular mechanism of NAFLD pathogenesis and valuable clues for the potential use of the constructed RNA network in effective diagnostic or management strategies of NAFLD.
Highlights
We aimed to construct “mRNAs—miRNAs—lncRNAs” regulatory network implicated in non-alcoholic fatty liver disease (NAFLD) pathogenesis based on in-silico analysis of microarray databases followed by its experimental validation in an NAFLD animal model
Analysis of the differentially expressed genes (DEGs) led to the identification of 1650 mRNAs between normal control and steatosis groups, 2814 mRNAs between steatosis and non-alcoholic steatohepatitis (NASH)
A number of studies have found that the NAFLD pathogenesis is related to a variety of signaling pathways including Hippo pathway [11] with the potential role of miRNAs and lncRNAs, which are crucial in disease development and progression [1]
Summary
Non-alcoholic fatty liver disease (NAFLD) is one of the common chronic liver diseases [1] with a global prevalence of ~25% [2]. In Egypt, it was reported in a cross-sectional study that NAFLD prevalence among children and adolescents was 15.8% [3]. NAFLD includes a spectrum of disorders ranging from liver simple steatosis (SS) to non-alcoholic steatohepatitis (NASH) that further increases the risk of developing cirrhosis and hepatocellular carcinoma [4]. NAFLD coexists with metabolic disorders, including obesity, type 2 diabetes (T2DM) and cardiovascular disease (CVD). The presence of NAFLD increases the incidence of T2DM while diabetes aggravates NAFLD to more severe disorders [5]. NAFLD patients with concomitant T2DM are at highest risk for CVD [6]
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