It has recently come to light that the epigenetic alteration of adenosine to inosine (A-to-I) RNA editing is a critical carcinogenic process in human malignancies. Its clinical importance and functional involvement in endometrial carcinoma (EC), however, are not well understood. Adenosine Deaminase family Acting on RNA1 (ADAR1) expression and Antizyme inhibitor 1 (AZIN1) RNA expression were analyzed to better understand their relationship to clinicopathological variables and patient outcomes in EC. The JHUCS-1 and the TU-ECS-1 EC cell lines were used to examine the biological and inhibitory effects of ADAR1 knockdown. There was a statistically significant correlation between ADAR1 and worse histology in EC (P=0.006) and lymph vascular space involvement (P=0.049). Poorer histology was also correlated with higher levels of AZIN1 RNA editing (P=0.012). AZIN1 RNA editing level was substantially linked with ADAR1 expression (R=0.729, R2=0.547, P<0.001). According to multivariate analysis, an independent predictor of prognosis in EC patients is a combination of high ADAR1 expression and AZIN1 RNA editing (P=0.015). A rise in Bak and apoptosis was observed in EC cells following ADAR1 knockdown. This was due to an uptick in the expression of MDA-5, RIG-I, PKR, and IRF-7. A poorer prognosis may be predicted by the presence of high ADAR1 expression in conjunction with AZIN1 RNA editing in EC. ADAR1 had therapeutic promise for those with EC.

Source: sciencedirect.com/science/article/pii/S0090825822003377