Global identification of miR-155 targets in skeletal muscle cells

Abstract

Muscular diseases are changes in skeletal muscle tissue caused by various defective structural proteins, deregulated molecular pathways and other mechanisms. Several research groups study these muscular alterations in order to clarify all the processes responsible for this condition that modify the skeletal muscles and leads to a progressive lethal degeneration of this tissue. The complexity of gene expression mechanisms that control this process suggests the involvement of additional regulatory molecules, such as microRNAs; these small RNA molecules encoded by the genome regulate various cellular processes of skeletal muscle, molecularly remodeling the global proteomic profile, through direct regulation of the mRNA target and/or epitranscriptional changes via transcription factors, kinases, phosphatases and so on. The microRNAs work in an orchestrated way to control a common biological function; this unique feature of microRNAs make them efficient tools for determining specific pathways involved in different conditions, including muscle diseases. Studies that analyzed the global expression of microRNAs in muscle tissue identified the dysregulated miR-155 in several muscular diseases, being suggested as a potential microRNA involved in the molecular alterations that affect the skeletal muscles of these patients. Therefore, the hypothesis of the present study is that miR-155 has direct targets and regulates transcription factors that molecularly change skeletal muscle cells. The objective of this work will be to identify the direct and indirect targets (targets altered by epitranscriptional regulation), using RNA-seq data and prediction tools such as miRWalk and miRTarBase, and to analyze the morphological alteration of these cells by immunofluorescence. The characterization of mRNAs regulated by miR-155 may reveal biological signaling pathways, and will contribute to the identification of possible therapeutic targets and treatments for patients with such muscular disorders.