Abstract

Long noncoding RNAs (lncRNAs) are a large class of regulatory RNAs with diverse roles in cellular processes. Thousands of lncRNAs have been discovered; however, their roles in the regulation of muscle differentiation are unclear because no comprehensive analysis of lncRNAs during this process has been performed. In the present study, by combining diverse RNA sequencing datasets obtained from public database, we discovered lncRNAs that could behave as regulators in the differentiation of smooth or skeletal muscle cells. These analyses confirmed the roles of previously reported lncRNAs in this process. Moreover, we discovered dozens of novel lncRNAs whose expression patterns suggested their possible involvement in the phenotypic switch of vascular smooth muscle cells. The comparison of lncRNA expression change suggested that many lncRNAs have common roles during the differentiation of smooth and skeletal muscles, while some lncRNAs may have opposite roles in this process. The expression change of lncRNAs was highly correlated with that of their neighboring genes, suggesting that they may function as cis-acting lncRNAs. Furthermore, within the lncRNA sequences, there were binding sites for miRNAs with expression levels inversely correlated with the expression of corresponding lncRNAs during differentiation, suggesting a possible role of these lncRNAs as competing endogenous RNAs. The lncRNAs identified in this study will be a useful resource for future studies of gene regulation during muscle differentiation.

Highlights

  • The major type of smooth muscle cells, vascular smooth muscle cells (VSMCs), are capable of converting between synthetic and contractile phenotypes [1, 2]

  • RNA sequencing (RNA-seq) data was obtained from VSMCs treated with platelet-derived growth factor (PDGF) and their untreated controls (GSE69637) [11]

  • PDGF induces the synthetic phenotype of VSMCs (Fig 1A) [1]

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Summary

Introduction

The major type of smooth muscle cells, vascular smooth muscle cells (VSMCs), are capable of converting between synthetic and contractile phenotypes [1, 2]. VSMCs exist as the differentiated and contractile type. In response to injury, VSMCs become de-differentiated into a more proliferative and synthetic phenotype.

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