The TCONS_00046732/chi-miR-135b-5p/PRLR regulatory axis promotes endometrial epithelial cells growth through the PI3K-Akt signaling pathway.

Abstract

Non-coding RNAs are considered key regulatory factors in biological and reproductive physiological processes in mammals. However, the molecular functions of long noncoding RNAs (lncRNAs) in regulating dynamic uterine development and reproductive capacity during sexual maturation remain unclear. This study analyzed the expression characteristics and molecular functions of lncRNAs in uterine tissues from 20 goats at four specific time points during sexual maturation: day 1 after birth (D1), 2 months (M2), 4 months (M4), and 6 months (M6), finding that stage-specific DE lncRNAs may regulate cell proliferation, apoptosis, hormone secretion, metabolism, and immune response through multiple action modes. Within the lncRNA-miRNA-mRNA network, a novel lncRNA, TCONS_00046732, associated with uterine development, exhibited significantly higher expression during sexual maturity compared to the prepubertal stage, correlating positively with PRLR and negatively with chi-miR-135b-5p. FISH and IF analyses revealed significant co-localization and distinct expression patterns of TCONS_00046732, chi-miR-135b-5p, and PRLR in the endometrial epithelium. Further experiments confirmed that TCONS_00046732 competitively binds to chi-miR-135b-5p to upregulate PRLR, thereby activating the PI3K-Akt signaling pathway, promoting primary endometrial epithelial cell proliferation, G1-to-S phase transition, and inhibiting apoptosis. These findings enhance our understanding of uterine molecular regulation and provide key insights into the molecular basis of goat sexual development.