Overexpression of androgen receptor signalling transactivator lncRNAs PRNCR1 and PCGEM1 are associated with the increased risk of PCOS

PCOS, a common disorder in reproductive aged women, characterized by hyperandrogenism. Hyperandrogenism can be attributed to the hyperactive androgen receptor (AR). Androgen receptor mediated signalling involves the association of multiple coregulators and any aberrant activity of these factors may disrupt the normal transcriptional activity of AR and hence may act as contributing factors in pathophysiology of hyperandrogenic disorders. LncRNAs PRNCR1 and PCGEM1 act as AR coactivators. The study was aimed at determining the association of these lncRNAs with PCOS. A total of 178 participants including 105 PCOS cases and 73 controls were recruited. The Anthropometric, Metabolic and hormonal characteristics of the participants were determined. Total RNA was isolated and reverse transcribed into cDNA. Quantitative real-time PCR was done to study the expression pattern of lncRNAs. The association between different parameters with the expression of PRNCR1 and PCGEM1 was determined by correlation analysis. The expression levels of PRNCR1 (PRNCR1, 5.28 (1.29-9.14) versus 1.07 (0.05-3.18); P < 0.001) (PCGEM1, 3.08 (0.29-8.79) versus 1.70 (0.116-3.73); P < 0.001) were significantly higher in Women with PCOS compared to controls. Furthermore, lncRNA PRNCR1 showed a positive correlation with testosterone (P < 0.001). ROC analysis showed a strong diagnostic performance of lncRNA PRNCR1 Optimal Cut off (Youden's Index) = 3.23, AUC = 0.988 (95% CI = 0.976-0.99) and Sensitivity = 0.91, Specificity = 1.00 and for PCGEM1 Optimal Cut off (Youden's Index) = 2.02, AUC = 0.86 (95% CI = 0.81-0.92) and Sensitivity = 0.82, Specificity: 0.90. Our results demonstrated that overexpression of AR coactivator lncRNAs PRNCR1 and PCGEM1 are associated with an increased risk of PCOS in Kashmiri women. These lncRNAs may act as important factors for the hyperactivation of AR and subsequent overexpression of AR regulated genes and thus may contribute towards the pathogenesis of PCOS and its clinical manifestations.