Long non-coding RNA366.2 controls endometrial epithelial cell proliferation and migration by upregulating WNT6 as a ceRNA of miR-1576 in sheep uterus.

Long non-coding RNAs (lncRNAs) play an important regulatory role in mammalian fecundity. Currently, most studies are primarily concentrated on ovarian lncRNAs, ignoring the influence of uterine lncRNAs on the fecundity of female sheep. In this study, we found a higher density of uterine glands and endometrial microvessel density (MVD) in high prolificacy group of Hu sheep compared to low prolificacy groups (p < 0.05) as well as an increased level of serum placental growth factor (PLGF). Hundreds of differentially expressed (DE) lncRNAs were identified in Hu sheep with different fecundity by RNA sequencing (RNA-seq), and their targets were enriched in some signaling pathways involved in endometrial functions, such as the estrogen signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, oxytocin signaling pathway, and Wnt signaling pathway. Furthermore, the underlying mechanisms of competitive endogenous RNA (ceRNA) of lncRNA366.2-miR-1576- WNT6 were determined by bioinformatics analysis. Functionally, our results indicated that lncRNA366.2 promoted endometrial epithelial cell (EEC) proliferation, migration, and growth factor expression by sponging miR-1576 to upregulate WNT6 expression and activate the Wnt/β-catenin pathway. Taken together, our research indicated the regulatory mechanism of the lncRNA366.2-miR-1576-WNT6 in EEC proliferation and migration. Furthermore, this study provides a new theoretical reference for the identification of candidate genes related to fecundity.