Roles of microRNAs in Regulating Apoptosis in the Pathogenesis of Endometriosis

Abstract

Endometriosis is a gynecologic disorder characterized by the presence of endometrial tissues outside the uterine cavity affecting reproductive-aged women. Previous studies have shown that microRNAs and their target mRNAs are expressed differently in endometriosis, suggesting that this molecule may play a role in the development and persistence of endometriotic lesions. microRNA (miRNA), a small non-coding RNA fragment, regulates cellular functions such as cell proliferation, differentiation, and apoptosis by the post-transcriptional modulation of gene expression. In this review, we focused on the dysregulated miRNAs in women with endometriosis and their roles in the regulation of apoptosis. The dysregulated miRNAs and their target genes in this pathophysiology were highlighted. Circulating miRNAs as potential biomarkers for the diagnosis of endometriosis have also been identified. As shown by various studies, miRNAs were reported to be a potent regulator of gene expression in endometriosis; thus, identifying the dysregulated miRNAs and their target genes could help discover new therapeutic targets for treating this disease. The goal of this review is to draw attention to the functions that miRNAs play in the pathophysiology of endometriosis, particularly those that govern cell death.

Keywords: apoptosis; dysregulated; endometriosis; microRNA; modulation.

Figure 1

Biogenesis mechanism of microRNA. (1) Transcription of the miRNA precursor under the influence of RNA Polymerase II into primary miRNA (pri-miRNA). (2) Maturation processing of pri-miRNA utilizes nuclear cleavage by Drosha and cofactor DCGR8 into pre-miRNA. (3) The pre-miRNA is transported from the nucleus into the cytoplasm by Exportin-5. (4) The pre-miRNA in the cytoplasm undergoes further maturation by Dicer cleaving one end of the miRNA to form a mature miRNA duplex. (5) The mature miRNA duplex transforms into single-stranded transcripts by helicase. (6) The single-stranded transcript miRNA incorporated with a ribonucleoprotein complex known as the RNA-induced silencing effector complex (RISC) and guide to complementary mRNA sequences that result in mRNA degradation, translational repression, or inhibition.

Figure 2

The list of downregulated miRNAs, and their target mRNAs involved in apoptosis in endometriosis [71,85,100,101,102,103,104,105,106,107].