Reconstruction and analysis of the lncRNA–miRNA–mRNA network based on competitive endogenous RNA reveal functional lncRNAs in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease with an unknown etiology, occurring in approximately 1.0% of general population. More and more studies have suggested that long non-coding RNAs (lncRNAs) could play important roles in various biological processes and be associated with the pathogenesis of different kinds of diseases including RA. Although a large number of lncRNAs have been found, our knowledge of their function and physiological/pathological significance is still in its infancy. In order to reveal functional lncRNAs and identify the key lncRNAs in RA, we reconstructed a global triple network based on the competitive endogenous RNA (ceRNA) theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and our previous paper. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using Cytoscape plug-in BinGO and Database for Annotation, Visualization, and Integration Discovery (DAVID), respectively. We found that the lncRNA-miRNA-mRNA network was composed of 7 lncRNA nodes, 90 mRNA nodes, 24 miRNA nodes, and 301 edges. The functional assay showed that 147 GO terms and 23 pathways were enriched. In addition, three lncRNAs (S5645.1, XR_006437.1, J01878) were highly related to RA, and therefore, were selected as key lncRNAs. This study suggests that specific lncRNAs are associated with the development of RA, and three lncRNAs (S5645.1, XR_006437.1, J01878) could be used as potential diagnostic biomarkers and therapeutic targets.

Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR‐125b with MCL‐1 by regulating mitochondrial apoptosis pathways in ovarian cancer

“…Furthermore, miR‐125b‐mediated mitochondrial apoptosis pathways also play important roles in chemotherapy drug‐induced apoptosis . The competitive endogenous RNA (ceRNA) theory for miRNA and lncRNA is currently widely accepted . To date, the role of LINC00152 in ovarian cancer is unclear, and whether LINC00152 achieves its role in cancer through the miR‐125b‐mediated mitochondrial pathway remains unclear.…”

Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

“…Under this ceRNA network, the lncRNAs and mRNAs are connected by their common target miRNAs [30]. In recent years, several studies have explored the underlying molecular mechanisms based on the ceRNA network in some diseases, such as breast cancer [32], ischemic stroke [33], and rheumatoid arthritis [34]. To identify lncRNAs significantly associated with POAG, in this study, the mRNA and lncRNA expression profiles of POAG patients were first used and combined with miRNA-target interactions to create a ceRNA network and to investigate the potential implications of these lncRNAs in the development of POAG.…”

Peer Review #2 of "Coordinative control of G2/M phase of the cell cycle by non-coding RNAs in hepatocellular carcinoma (v0.1)"

“…Non-coding RNAs such as lncRNAs and miRNAs have been proven to participate in the regulation of gene expression through competition for endogenous RNA networks with mRNA (Kartha & Subbaya 2014). The interaction between these two ncRNAs plays an important role in tumor development (Jiang et al 2017;Wu et al 2016). At present, the specific molecular mechanism of the interaction between lncRNA and miRNA is speculated to be one of two possibilities:1. because lncRNAs and mRNAs have a similar structure, a miRNA can specifically bind to its 3' UTR and down-regulate lncRNA expression through a mechanism similar to that of mRNA regulation (Shi et al 2013); or 2. studies have confirmed that lncRNAs can competitively target miRNAs to inhibit the expression of miRNAs, thereby reducing their inhibitory effect on target genes (Salmena et al 2011).…”