Identification of LncRNA Linc00513 Containing Lupus-Associated Genetic Variants as a Novel Regulator of Interferon Signaling Pathway

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by augmented type I interferon signaling. High-throughput technologies have identified plenty of SLE susceptibility single-nucleotide polymorphisms (SNPs) yet the exact roles of most of them are still unknown. Functional studies are principally focused on SNPs in the coding regions, with limited attention paid to the SNPs in non-coding regions. Long non-coding RNAs (lncRNAs) are important players in shaping the immune response and show relationship to autoimmune diseases. In order to reveal the role of SNPs located near SLE related lncRNAs, we performed a transcriptome profiling of SLE patients and identified linc00513 as a significantly over expressed lncRNA containing functional SLE susceptibility loci in the promoter region. The risk-associated G allele of rs205764 and A allele of rs547311 enhanced linc00513 promoter activity and related to increased expression of linc00513 in SLE. We also identified linc00513 to be a novel positive regulator of type I interferon pathway by promoting the phosphorylation of STAT1 and STAT2. Elevated linc00513 expression positively correlated with IFN score in SLE patients. Linc00513 expression was higher in active disease patients than those inactive ones. In conclusion, our data identify two functional promoter variants of linc00513 that contribute to increased level of linc00513 and confer susceptibility on SLE. The study provides new insights into the genetics of SLE and extends the role of lncRNAs in the pathogenesis of SLE.

Prognostic and Predictive Values of the Autophagy Signature in Colon Cancer

“…For instance, AP006621.2 and STAG3L5P-PVRIG2P-PILRB were found to be associated with the expression of VEGFA in COAD. VEGFA is known to be a pivotal oncogene in various cancers [43]. PCAT6 was found to be associated with expression of FAS, and FAS is found to be an initiator of in ammation for cancers [44].…”

“…lncRNAs dominate the upstream portion of the RNA network and function as primary effectors of mRNAs, and several lncRNAs are identi ed as potential prognostic factors in COAD [20,30]. Among these 14 lncRNAs in the model, PCAT6, CASC9, MIR4435-2HG, SNHG16, and LINC00513 have been reported to play a role in the pathogenesis and prognosis of various cancer types (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). For example, CASC9 has been reported to be upregulated and conferred an oncogenic function in human hepatocellular carcinoma, oral carcinoma, gastric cancer, colorectal cancer, and esophageal cancer [28,[31][32][33].…”

A prognostic five immune-related long noncoding RNA signature for patients with colon cancer

“…Our results are consistent with their ndings that ELFN1-AS1 played tumor promoting role in COAD. LINC00513 is intergenic lncRNA and played important roles in lupus pathogenesis by promoting IFN signaling pathway [17]. However, little is known about the role of LINC00513 in cancer.…”

Exploring the Role of Non-Coding RNAs in the Pathophysiology of Systemic Lupus Erythematosus

“…The role of this SNP in the regulation of apoptosis has also been verified in clinical samples [ 28 ]. The assessment of transcript signatures in SLA patients identified the lcnRNA linc00513 as significantly upregulated relative to healthy controls [ 32 ]. Interestingly, linc00513, which has also been recognized as a regulator of the type I interferon pathway [ 32 ], encompasses a functional risk locus for SLE in its promoter region.…”

“…The assessment of transcript signatures in SLA patients identified the lcnRNA linc00513 as significantly upregulated relative to healthy controls [ 32 ]. Interestingly, linc00513, which has also been recognized as a regulator of the type I interferon pathway [ 32 ], encompasses a functional risk locus for SLE in its promoter region. Notably, the risk alleles of the rs205764 and rs547311 SNPs increase the promoter activity of linc00513, resulting in the over-expression of this lncRNA in SLA patients.…”