miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor

Abstract

Labor is initiated as a result of hormonal changes that are induced by the activation of the inflammatory response and a series of biochemical events. The amnion, which is the primary source of prostaglandin E2 (PGE2), plays an important role in the process of labor. In the present study, we uncovered a pathway in which c-fos, cyclooxygenase-2 (COX2) and miR-144 function as hormonal modulators in the amnions of pregnant mice and humans. miR-144 down-regulated the synthesis of PGE2 during pregnancy by directly and indirectly inhibiting COX2 expression and by directly inhibiting the expression of c-fos, a transcriptional activator of COX2 and miR-144. Estrogen (E2) activated c-fos, thus promoting the expression of miR-144 and COX2 during labor. However, the increase in COX2 resulted in the partial inhibition of COX2 expression by miR-144, thereby slightly reducing the secretion of PGE2. These observations suggest that miR-144 inhibits PGE2 secretion by section to prevent the initiation of premature labor. Up-regulated expression of miR-144, c-fos and COX2 was also observed both in preterm mice and in mice undergoing normal labor. In summary, miR-144, c-fos and COX2 play important roles in regulating PGE2 secretion in the amnion during pregnancy and labor.

Prevention of lipopolysaccharide-induced preterm labor by the lack of CX3CL1-CX3CR1 interaction in mice

“…In both term labor and PTL, PGs play essential roles in the processes of uterine contractility, membrane rupture, and cervical ripening [ 64 – 66 ]. PGs are generated by the enzymatic action of PTGS, known as COX.…”

MicroRNA-144-3p targets relaxin/insulin-like family peptide receptor 1 (RXFP1) expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis

“…Previously, it has been shown that the AP-1 complex is one of the key regulators of miR-144 locus (25,26). Furthermore, to determine whether AP-1 may be involved in regulation of miR-144-3p in lung fibroblasts, we silenced c-Jun or c-Fos by siRNA (Fig.…”

Suppression of MicroRNA-144 Promotes CXCR4 and CXCL12 Expression and Downregulates Apoptosis in Ovarian Cancer Cells

“…In this study, we used CLX as a positive control to show COX-2 inhibition. It has been shown that miR-144 down-regulated the synthesis of PGE2 during pregnancy by directly and indirectly inhibiting COX-2 expression in human and mice (Li et al, 2016). In this study, suppression of miR-144 triggered COX-2 protein and gene expression and induced COX-2 promoter activity in ovarian cancer cells.…”