FUNCTIONAL DISSECTION OF LONG NON-CODING RNA NETWORKS IN CELLULAR DIFFERENTIATION PATHWAYS

Abstract

Long non-coding RNAs (lncRNAs) are important regulators of gene expression, which play important roles in lineage specification and differentiation of cells. Although there are considerable progresses in the identification of single lncRNAs in developmental processes, little is known about how these regulatory networks interact to guide the various developmental pathways. This paper will use a multi-level analysis system to functionally deconstruct lncRNA-mediated regulatory processes with an integrated approach to transcriptomic profiling, network modeling, and pathway enrichment analysis. RNA-sequencing data publicly accessible were processed to reveal differentially expressed lncRNAs in cellular differentiation and then lncRNA-mRNA and competing endogenous RNA (ceRNA) networks were constructed to understand the key regulatory interactions. Pathway and functional enrichment analyses indicated a highly complex role of lncRNAs in central signaling pathways (TGF-B/SMAD, WNT/-catenin, and BMP) and their functions as key regulators of transcriptional and post-transcriptional regulation. Topology analysis of the network revealed various hub lncRNAs which might have functional relevance in the lineage commitment and dynamics of differentiation. These results indicate that cellular differentiation is regulated by complicated, multi-layered lncRNA regulatory networks and not individual gene-specific processes. The research offers a systems-level view of the lncRNA role which offers important understanding of developmental biology as well as provides potential regenerative medicine and disease modelling targets.