New Therapeutics in Endometriosis: A Review of Hormonal, Non-Hormonal, and Non-Coding RNA Treatments

Abstract

Endometriosis is defined as endometrial-like tissue outside the uterine cavity. It is a chronic inflammatory estrogen-dependent disease causing pain and infertility in about 10% of women of reproductive age. Treatment nowadays consists of medical and surgical therapies. Medical treatments are based on painkillers and hormonal treatments. To date, none of the medical treatments have been able to cure the disease and symptoms recur as soon as the medication is stopped. The development of new biomedical targets, aiming at the cellular and molecular mechanisms responsible for endometriosis, is needed. This article summarizes the most recent medications under investigation in endometriosis treatment with an emphasis on non-coding RNAs that are emerging as key players in several human diseases, including cancer and endometriosis.

Keywords: angiogenesis; apoptosis; cell migration; cell proliferation; endometriosis; fibrosis; inflammation; non-coding RNA; stem cells.

Figure 1

Schematic illustration of the complexity of ncRNA gene networks. In this example, only two splice variants of Gene 1 are translated into proteins. These protein products can be regulated by ncRNAs encoded by Genes 2, 3, and 4, which interact with Gene 1 at the RNA/protein level. Gene 2 encodes miRNAs interacting with mRNAs (mRNA 1.1 and mRNA 1.2). Gene 3 encodes for lncRNAs interacting with the protein products of Gene 1 and acts as a miRNA sponge. Gene 4 encodes for circRNAs serving as a sponge or as a decoy for any RNA-binding event that indirectly regulates Gene 1 products, such as lncRNA or miRNA interactions.

Figure 2

The aberrant expression of several ncRNAs in endometriosis promotes angiogenesis, apoptosis, cell proliferation, cell invasion, cell migration, including the epithelial–mesenchymal transition (EMT), inflammation, and estrogen and progesterone dysregulation. MiRNAs exert their function through modulation of parental gene expression; lncRNAs and circRNAs act as miRNA sponges or RNA decoys, while lncRNAs interact with the protein products of genes and/or act as miRNA sponges.