miR-29c is downregulated in the ectopic endometrium and exerts its effects on endometrial cell proliferation, apoptosis and invasion by targeting c-Jun

Abstract

Abstract. Endometriosis is a prevalent and complex gynecological disease which affects 10% of women of reproductive age. Certain studies have suggested that a substantial number of microRNAs (miRNAs or miRs) are aberrantly or differentially expressed in the ectopic endometrium. To date, to the best of our knowlewdge, there is no report available on the role of miR-29 in the endometrium. In this study, we investigated the expression of the miR-29 family in the endometrium samples from women without endometriosis, as well as in paired ectopic and eutopic endometrium samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results revealed that miR-29c was differentially expressed in the paired eutopic and ectopic endometrium samples. In addition, c-Jun was differentially expressed in the ectopic and eutopic endometrial tissues as determined by western blot analysis. Furthermore, the role of miR-29c in endometrial cell proliferation, invasion and apoptosis was examined in vitro. The results revealed that miR-29c exerted its effects on endometrial cells by suppressing cell proliferation and invasion, as well as promoting cell apoptosis. Furthermore, it was found that c-Jun was a novel target of miR-29c, and c-Jun reversed the effects of miR-29c on the proliferation, invasion and apoptosis of endometrial cells. To the best of our knowledge, this study is the first to identify miR-29c as a suppressor of endometriosis. Taken together, our results suggest that miR-29c exerts its effects on endometrial cell proliferation, apoptosis and invasion by inhibiting the expression of c-Jun. Our data may provide a novel potential therapeutic target for the treatment of endometriosis.

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). These findings corroborate with the literature and point toward the potential role of EVs in modulating disease pathophysiology.…”

Redox regulation of microRNAs in endometriosis-associated pain

“…The majority of these miRNAs are located in the genomically unstable sites, lending to their targeting of oncogenes, tumor suppressor genes, angiogenesis, and genes associated with inflammation or immune function [62], [76]. Functional pathway analyses of miRNA targets showed alterations in genes such as aromatase ( CYP-19 ) and COX-2 as well as those involved in apoptosis and cell-signaling to be differentially expressed in endometriosis [60], [61], [77], [78], [79]. For example, the downregulation of migration inhibitory factor (MIF) in ectopic endometriotic lesions compared to eutopic endometrium has been attributed to the upregulation of miR-451 [80].…”

MicroRNAs and Endometriosis: Distinguishing Drivers from Passengers in Disease Pathogenesis

“…More recently, Long et al 25 also investigated the expression of the miR-29 family in the endometrium samples from women without endometriosis, as well as in paired ectopic and eutopic endometrium samples. As opposed to earlier studies, 22–24 these authors observed a decrease in lesion expression of miR-29c .…”