mRNA-miRNA-lncRNA Regulatory Network in Nonalcoholic Fatty Liver Disease

• Main Authors: Marwa Matboli, Shaimaa H. Gadallah, Wafaa M. Rashed, Amany Helmy Hasanin, Nada Essawy, Hala M. Ghanem, Sanaa Eissa
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: NAFLD; Non-Alcoholic SteatoHepatitis (NASH); Hippo signaling; miRNAs; lncRNAs; ncRNAs network
• Online Access: https://www.mdpi.com/1422-0067/22/13/6770

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 (<i>YAP1, FOXA2, AMOTL2, TEAD2, SMAD4</i> and <i>NF2</i>), two miRNAs (<i>miR-650</i> and <i>miR-1205</i>), and two lncRNAs (RPARP-AS1 and <i>SRD5A3-AS1</i>) 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.