Functional prediction of long non-coding RNAs using transcriptome data in cancer-associated cachexia

Abstract

Cancer-associated cachexia is a syndrome characterized by involuntary weight loss, mainly due to loss of muscle mass. It is a multifactorial metabolic syndrome associated with specific tumor types, but the variation causes in the prevalence and severity of cachexia are still unknown. RNA sequencing (RNA-Seq) revolutionized transcriptomic studies and allowed a better understanding of the mechanisms associated with muscle loss in this condition. However, the muscle atrophy etiology in cancer cachexia involves complex cellular and molecular mechanisms that still need to be fully elucidated. Long non-coding RNAs (lncRNAs) constitute a class of RNAs that act by different mechanisms in transcriptional and post-transcriptional regulation. In this context, lncRNAs are potential candidates for regulating pathways related to muscle atrophy, due to their wide action in muscle cells. Thus, this project aims to identify, characterize and predict the function of lncRNAs potentially associated with muscle atrophy in cancer-associated cachexia. Initially, public transcriptome (RNA-Seq) data from muscle tissue in mice and humans with cancer-associated cachexia will be selected from GEO (https://www.ncbi.nlm.nih.gov/geo/) and ENA (https://www.ebi.ac.uk/ena/). Subsequently, the transcriptional lncRNA profile for each RNA-Seq dataset will be analyzed, and the potential action mechanisms of selected lncRNAs will be identified with LncRNA-mRNA co-expression, LncRNA-Protein and LncRNA-DNA analysis. Finally, lncRNAs expressed in skeletal muscle cells will be selected using data available from the Single-Cell Muscle Project (http://scmuscle.bme.cornell.edu/) in order to perform functional studies using C2C12 cells. Our study aims to identify lncRNAs in regulatory networks and molecular pathways involved in muscle wasting. Additionally, our results may indicate potential targets for the development of future therapeutic strategies aimed at minimizing muscle wasting in patients with cancer-associated cachexia.