The Relationship and Expression of miR-451a, miR-25-3p and PTEN in Early Peritoneal Endometriotic Lesions and Their Modulation In Vitro

Abstract

Background: miR-451a can function as a tumor suppresser and has been shown to be elevated in both endometriotic lesion tissue and serum from women with endometriosis. To further explore the role of miR-451a in the pathophysiology of endometriosis, specifically, further evaluating its association with the tumor suppressor, phosphatase and tensin homolog (PTEN), we examined their expression in individual endometriotic lesion tissue to gain insight into their relationship and further explore if miR-451a regulates PTEN expression. Methods: A total of 55 red, peritoneal endometriotic lesions and matched eutopic endometrial specimens were obtained from 46 patients with endometriosis. miR-451a, miR-25-3p and PTEN mRNA levels were assessed by qRT-PCR and reported for each matched eutopic and ectopic sample. To evaluate miR-451a and miR-25-3p expression of miR-25-3p and PTEN, respectively, 12Z cells (endometriotic epithelial cell line) were transfected and miR-25-3p expression was assessed by qRT-PCR, while PTEN protein expression was assessed by Western blotting. Results: PTEN and miR-25-3p expression exhibited an inverse relationship, as did miR-25-3p and miR-451a in individual lesions. Over-expression of miR-451a in 12Z cells resulted in down-regulation of miR-25-3p, while up-regulation of miR-25-3p resulted in down-regulation of PTEN protein expression. Conclusions: By assessing individual endometriotic lesion expression, we discovered an inverse relationship between miR-451a, miR-25-3p and PTEN, while in vitro cell transfection studies suggest that miR-451a may regulate PTEN expression via modulating miR-25-3p.

Dissecting the miR-451a-Mif Pathway in Endometriosis Pathophysiology Using a Syngeneic Mouse Model: Temporal Expression of Lesion Mif Receptors, Cd74 and Cxcr4

“…It is tempting to speculate that the elevated expression of Cd74 may occur in response to the reduced levels of Mif ligand [ 20 ] in an attempt to maintain lesion survival. Accumulating data from our lab [ 18 , 20 , 44 , 45 ] support the notion that increased levels of endometriotic lesion miR-451a function to curtail lesion survival by at least impart reducing Mif expression but other indirect targets of miR-451a which impact lesion survival [ 44 ] may come into play as well. Alternatively, loss of miR-451a may lead to changes in other miRNAs which could lead to enhanced Cd74 transcript expression.…”

“…Alternatively, loss of miR-451a may lead to changes in other miRNAs which could lead to enhanced Cd74 transcript expression. We recently reported that miR-451a decreases expression of a miRNA ( miR-25-3p ) in vitro which is a bonafide regulator of PTEN expression [ 45 ]. Thus, it may be likely that expression levels of miR-451a (either absence at the time of lesion establishment or elevation which occurs as lesions age) may influence the expression of other miRNAs which could impact Cd74 expression.…”