Expression analysis of Wnt signaling pathway related lncRNAs in periodontitis: A pilot case-control study

Abstract

LncRNAs are involved in the modulation of several signaling pathways which have a crucial effect in the differentiation of periodontal ligament cells and the induction of cementum regeneration. Autophagy and Wnt signaling are two important pathways with a wide range of interrelationships associated with periodontitis. We chose four lncRNAs based on their potential interaction with these two pathways. We examined the expression of FOXD2-AS1, NNT-AS1, GAS8-AS1, and CCAT1 lncRNAs in tissues and blood specimens of patients with periodontitis and unaffected controls using qRT-PCR. Expression amounts of FOXD2-AS1 were lower in blood of cases compared with controls (relative expression (RE) = 0.08, P value<0.001). Tissue expression of FOXD2-AS1 was similar between cases and controls. Difference in blood levels of FOXD2-AS1 was significant among female subjects (RE = 0.07, P-value = 0.01), but not among male subjects. In addition, we reported lower levels of NNT-AS1 in blood samples of cases versus controls (RE = 0.25, P value = 0.05). But such a pattern was not seen in tissue samples. Expression of GAS8-AS1 was lower in both tissue and blood specimens of patients compared with control (RE = 0.49, P value = 0.02 and RE = 0.32, P value = 0.03 for tissue and blood specimens, respectively). Moreover, the differences in blood expression of GAS8-AS1 were significant in female patients compared with female controls (RE = 0.25, P-value = 0.04). Expression of CCAT1 was significantly lower in both gingival tissue and blood samples of patients compared with control (RE for tissue samples = 0.36, P-value = 0.02 and RE for blood samples = 0.33, P-value = 0.02). This pattern of expression was also detected in tissue specimens obtained from male persons (RE = 0.23, P value = 0.02) and blood samples acquired from female patients compared with corresponding control samples (RE = 0.21, P value<0.001). FOXD2-AS1 showed the best AUC values for distinguishing periodontitis in blood samples (AUC = 0.78). Combination of transcript levels of all four lncRNAs increased the diagnostic power to 0.81 and 0.74 in the gingival tissues and blood specimens, respectively. Our study demonstrates dysregulation of several lncRNAs in the periodontitis. These transcripts might partake in the pathogenesis of periodontitis and could have a possible correlation with autophagy and Wnt signaling pathways.