Long Non-Coding RNA TUG1 Gene Polymorphism and TUG1 Expression Level as Molecular Biomarkers of Systemic Lupus Erythematosus and Lupus Nephritis.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2023-09-19 DOI:10.3390/ncrna9050056
Gehan Abd-Elfatah Tawfeek, Heba Kasem, Eman Ali Abdallah, Mohammed Almulhim, Abdullah Almulhim, Mohammed Albarqi, Khaled Mohamed Amin Elzorkany
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Abstract

Long non-coding RNA (lncRNA) TUG1 acts as a proto-oncogene, allowing the proliferation of tumor cells, and it has been related to inflammation. Therefore, we aimed in this study to investigate for the first time the role of TUG1 gene polymorphism and the TUG1 level as biomarkers in systemic lupus erythematosus (SLE) and their link to lupus nephritis 145 SLE. A total of 145 healthy controls were subjected to clinical and laboratory evaluation. The disease activity was assessed by the SLE disease activity index (SLEDAI) score. SLE patients were divided into two subgroups according to the presence of lupus nephritis. The TUG1 gene polymorphisms rs5749201 and rs886471 were determined by Sanger sequencing, and TUG1 expression was assessed by qRT-PCR. There was a significant increase in the risk of SLE AA, TA, dominant genotypes, and the A allele of rs5749201 (p < 0.001) by 4.9-, 10.1-, 6.5-, and 2.5-fold in comparison to the relative control. GG and TG, dominant genotypes and the G allele of rs886471 (p < 0.01) increased the risk by 5.09-, 11.9-, 6.5-, and 2.6-fold. AA, A allele, dominant and recessive rs5749201genotypes increased the risk of lupus nephritis by 16.6-, 7.4-, 7.1-, and 12.2-fold, respectively (p < 0.05). GG, dominant and recessive genotypes, and the G allele of rs886471 increased the risk of lupus nephritis by 17.04-, 7.8-, 9.4-, and 6.08-fold, respectively (p < 0.05). Additionally, the AG haplotype increased the risk of SLE and lupus nephritis by 2.7- and 7.8-fold, respectively. The AA rs5749201 and GG rs886471 variants are significantly associated with more severe disease (p < 0.001). TUG1 expression was significantly higher in SLE than in the control and in the lupus nephritis than in non-lupus nephritis cases (p < 0.05). Interestingly, AA rs5749201 and GG rs886471 were significantly associated with higher TUG1 levels (p < 0.001). It was also found that AA rs5749201 and high SLEDAI were predictors of lupus nephritis. Overall, our findings illustrated for the first time that TUG1 gene rs5749201 and rs886471 variants were associated with increased risk of SLE, more severe disease, and lupus nephritis, and the TUG1 level could be used as a diagnostic biomarker of SLE and lupus nephritis.

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作为系统性红斑狼疮和狼疮性肾炎分子生物标志物的长非编码RNA TUG1基因多态性和TUG1表达水平。
长非编码RNA(lncRNA)TUG1作为原癌基因,允许肿瘤细胞增殖,它与炎症有关。因此,我们在本研究中首次探讨了TUG1基因多态性和TUG1水平作为系统性红斑狼疮(SLE)生物标志物的作用及其与狼疮性肾炎145 SLE的关系。共对145名健康对照进行了临床和实验室评估。疾病活动性通过SLE疾病活动性指数(SLEDAI)评分进行评估。根据狼疮性肾炎的存在,将SLE患者分为两个亚组。通过Sanger测序测定TUG1基因多态性rs5749201和rs886471,并通过qRT-PCR评估TUG1的表达。与相对对照相比,SLE AA、TA、显性基因型和rs5749201的a等位基因的风险显著增加了4.9-、10.1-、6.5-和2.5倍(p<0.001)。GG和TG、rs886471的显性基因型和G等位基因(p<0.01)使患狼疮性肾炎的风险增加了5.09、11.9、6.5和2.6倍。AA、A等位基因、显性和隐性rs5749201基因型使患狼疮肾炎的风险分别增加了16.6、7.4、7.1和12.2倍(p<0.05),此外,AG单倍型使SLE和狼疮性肾炎的风险分别增加2.7倍和7.8倍。AA rs5749201和GG rs886471变异体与更严重的疾病显著相关(p<0.001)。TUG1在SLE中的表达显著高于对照组,在狼疮性肾炎中的表达明显高于非狼疮性肾炎(p<0.05)。有趣的是,AA rs5749201和GG rs886471与较高的TUG1水平显著相关(p<0.001)。还发现AA rs574920 1和高SLEDAI是狼疮性肾炎的预测因素。总体而言,我们的研究结果首次表明,TUG1基因rs5749201和rs886471变异与SLE、更严重疾病和狼疮性肾炎的风险增加有关,TUG1水平可作为SLE和狼疮性肾小球肾炎的诊断生物标志物。
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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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