Circulating miRNAs in Murine Experimental Endometriosis: Decreased Abundance of let-7a

Abstract

Endometriosis is a chronic disease that commonly affects women of reproductive age; however, diagnosis is often delayed due to lack of appreciation of early signs and symptoms. Development of a noninvasive biomarker would significantly reduce delays in diagnosis and treatment. Circulating microRNAs (miRNAs) have been implicated as biomarkers for several diseases including endometriosis. Here, we use an miRNA array to investigate differential miRNA abundance in the serum of mice after induction of experimental endometriosis. let-7a-5p was decreased in the serum of mice with endometriosis. let-7b-5p, c-5p, and e-5p also showed a trend toward downregulation. Serum let-7 family miRNA shows similar dysregulation in endometriosis in both humans and mice. Diminished circulating let-7 implies a complex regulation that potentially involves multiple organs. Further investigation is necessary to determine the functional roles of let-7 miRNAs in this disease.

Extracellular vesicles from endometriosis patients are characterized by a unique miRNA-lncRNA signature

“…Previous work in endometriosis has also corroborated our findings, with a report indicating that let-7a is downregulated in serum in a mouse model of endometriosis (28), miR-23a is upregulated in ectopic compared with eutopic tissues (29), and differential expression of miR-143 and -320a in endometriomas is shown compared with endometrium (24). Our qPCR-based validation studies involved additional DE miRNAs from Supplemental Table 1 of commonly grouped DE miRNAs such as miR-29c, which has been reported to be downregulated in ectopic endometrium (30), as well as miR-451, which is elevated in endometriotic tissue compared with paired eutopic endometrium from women with disease in the patient cohort from (29) (Ectopic > Normal and Eutopic > Normal tissues as detected in the small RNA-seq data).…”

The Systemic Effects of Endometriosis

“…75 In 2008, miRNA analysis by Ohlsson Teague et al demonstrated that 22 miRNAs were differentially expressed in human endometriosis lesions compared with eutopic endometrium. 76 Since then, miRNAs in endometriosis have been investigated as endometriosis biomarkers analysis 8,77,78 and for insight into disease proliferation and pathogenesis. 76,[79][80][81][82][83][84][85] In addition to affecting the endometriosis lesion microenvironment, miRNAs are secreted into the vasculature near the lesion and alter systemic serum miRNA concentrations.…”

“…76,[79][80][81][82][83][84][85] In addition to affecting the endometriosis lesion microenvironment, miRNAs are secreted into the vasculature near the lesion and alter systemic serum miRNA concentrations. 8,77,78 In 2016, miRNA microarray and qPCR analysis of patient serum samples demonstrated that 10 microRNAs were more than 10-fold aberrantly regulated, Mir-125b-5p, miR-150-5p, miR342-3p, miR-145-5p, miR-143-3p, miR-500a-3p, miR-451a, miR18a-5p, miR-3613-5p, and miR-6755-3p. 8 Several of these circulating miRNAs have been correlated with chemoresistant breast cancer, breast cancer development, and suppression of the differentiation of mesenchymal stem cells, a possible source of endometriosis lesions.…”

microRNA Let‐7b: A Novel treatment for endometriosis

“…Distinct miRNA expression profiles have been identified in microarray studies of eutopic and ectopic endometrial tissue samples . We previously reported that circulating microRNAs, including Let‐7b‐5p, were significantly decreased in the serum of patients with endometriosis as well as animal models of the disease . Further, we have reported decreased Let‐7 family members in endometriosis tissue where they are involved in the regulation of genes such as KRAS and aromatase .…”