Circulating Micro-RNAs as Diagnostic Biomarkers for Endometriosis: Privation and Promise

Abstract

Endometriosis represents a major medical concern in women of reproductive age. One of the remaining major hurdles for successful treatment of endometriosis is the limitation of the process of timely disease diagnosis. A simple blood test for endometriosis-specific biomarkers would offer a more timely accurate diagnosis for the disease, thus allowing for earlier treatment intervention. Although there have been considerable efforts to identify such biomarkers, no clear choice for such noninvasive diagnostic tools has been identified. Micro-RNAs are small noncoding RNAs that have been evaluated intensively as biomarkers for several diseases, and they may hold promise for a diagnosis of endometriosis. In this review, we highlight the need for noninvasive testing for endometriosis, discuss the potential use of micro-RNAs as diagnostic tools for this disease, and consider potential limitations in the use of these small RNA molecules as diagnostic markers for endometriosis.

Keywords: Diagnostic biomarker; Endometriosis; microRNA.

Figure 1

Biogenesis, mechanism of action and extracellular secretion of microRNA (miRNA). Pri-miRNA are transcribed by polymerase II (POL II) in the nucleus and processed by Drosha into pre-miRNA. An alternative non-canonical pathway is generated by certain debranched introns, called ‘mirtrons’, which undergo splicing and mimic the structural features of pre-miRNA, entering the miRNA-processing pathway without Drosha-mediated cleavage. Exportin transports pre-miRNA molecules to the cytoplasm, where DICER generates miRNA–miRNA* duplexes. These are converted into single-strand mature miRNA and incorporated into the RNA-induced silencing complex (RISC), which sequence-specifically binds to miRNA target sites on mRNA transcripts, effecting mRNA cleavage and degradation or, if the alignment if imperfect, repression of gene translation. Pre-miRNA are exported from cells via two mechanisms: (i) in multivesicular bodies (MVB), which release miRNA into the circulation via fusion with the cell membrane; and (ii) in association with RNA-binding proteins such as nucleophosmin 1 (NPM1), argonaute 2 (Ago2) or high-density lipoprotein (HDL). Circulating miRNA are taken up by the recipient cells either by endocytosis or, if protein bound, by receptor-mediated interactions at the cell surface. miRNA internalized by recipient cells can inhibit the expression of target protein-coding genes.