lincRNA RP24-315D19.10 promotes endometrial decidualization via upregulation of hnRNPA2B1

Decidualization is a critical process for successful pregnancy. Disorders in this process are tightly associated with adverse pregnancy outcomes including spontaneous abortion. However, the potential molecular mechanisms of lncRNAs underlying this process are yet to be fully elucidated. In this study, we utilized RNA sequencing (RNA-seq) to identify differentially expressed lncRNAs during endometrial decidualization with a pregnant mouse model. Based on RNA-seq analysis, weighted gene co-expression network analysis (WGCNA) was performed to construct the lncRNA-mRNA co-expression network and to identify decidualization-associated hub lncRNAs. Through comprehensive screening and validation, we identified a novel lncRNA, RP24-315D19.10 and studied its function in primary mouse endometrial stromal cells (mESCs). lncRNA RP24-315D19.10 was highly expressed during decidualization. Knockdown of RP24-315D19.10 significantly inhibited mESCs decidualization in vitro. Mechanistically, RNA pull-down and RNA immunoprecipitation assays indicated that cytoplasmic RP24-315D19.10 could bind to hnRNPA2B1, thereby upregulating hnRNPA2B1 expression. Site-directed mutagenesis followed by biolayer interferometry analysis additionally illustrated that hnRNPA2B1 protein specifically bound to the ~-142ccccc~-167 region of the RP24-315D19.10 sequence. hnRPA2B1 deficiency impairs mESCs decidualization in vitro and we found that the inhibition in decidualization caused by RP24-315D19.10 knockdown was rescued by hnRNPA2B1 overexpression. Moreover, the expression of hnRNPA2B1 in spontaneous abortion women with deficient decidualization was significantly lower than that in healthy individuals, suggesting that hnRNPA2B1 may be involved in the development and progression of spontaneous abortion caused by decidualization failure. Collectively, our study indicates RP24-315D19.10 is a critical regulator for endometrial decidualization and RP24-315D19.10-regulated hnRNPA2B1 might be a new mark of decidualization-related spontaneous abortion.