The Potential Regulatory Mechanism of lncRNA 122K13.12 and lncRNA 326C3.7 in Ankylosing Spondylitis

Abstract

This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation [area under the ROC curve (AUC) = 0.739 (0.609–0.870) and p = 0.003], and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation [AUC = 0.870 (0.780–0.959) and p < 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737)]. In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.

Expression of long non‑coding RNA NONHSAT227927.1 and its effect on the JAK2/STAT3 signaling pathway and inflammation in patients with ankylosing spondylitis

“…They primarily participate in the manipulation of gene expression after gene transcription and post-transcription, and also are implicated in the progression of AS. Li et al ( 34 ) found that MEG3 was downregulated in patients with AS, and Wang et al ( 21 ) observed that lncRNA H19 was also related to the pathogenesis of inflammatory diseases. The data obtained by Gong et al ( 35 ) documented that lncRNAs (326C3.7 and 122K13.12) elevated considerably in AS patients with osseous bridges.…”

“…LncRNAs have attracted increasing attention in the field of AS. Previously ( 21 ), lncRNA NONHSAT227927.1 was identified by the authors as a key lncRNA involved in the immune-inflammation of AS through high-throughput sequencing and bioinformatics analysis. Despite intensive studies on lncRNAs, their functional and pathological significance remains largely unknown.…”

Screening Key lncRNAs of Ankylosing Spondylitis Using Bioinformatics Analysis

“…One recent study showed that peripheral blood lncRNA NONHSAT118801.2 and NONHSAT183847.1 levels were reduced in patients with AS and negatively correlated with CRP and ESR levels in these individuals, suggesting a potential protective role of lncRNAs in this pathological context. 21 RNA-sequencing data revealed that lncRNA contributed to disease progression of AS, 22 as lncRNA–mRNA interaction was common. This study identified three upregulated DElncRNAs (linc00304, linc00926, and MIAT) in three AS GEO databases and validated the differential expression of those lncRNAs by qRT-PCR with 44 samples.…”

A review of long non-coding RNAs in ankylosing spondylitis: pathogenesis, clinical assessment, and therapeutic targets

“…In an earlier study, the researchers used high-throughput sequencing and bioinformatics analysis to identify the lncRNA NONHSAT227927.1 as a significant player in the inflammatory processes of AS through the application of ( Wang et al, 2021 ). Subsequent experiments revealed that the levels of IL-17 and IL-23 notably increased and the IL-10 level decreased with the overexpression of NONHSAT227927.1.…”

“…Similar to ESR and CRP, linc00304 was identified as independent risk factors for AS activity. They also found that lncRNA 326C3.7 was independently correlated with bone bridge formation, with an AUC of 0.739, which can aid in predicting the occurrence of bone bridge formation ( Wang et al, 2021 ).…”