Potential Role of microRNA 410 and BIRC7 Pathways in Recurrent Spontaneous Miscarriage

Overview

The definition of recurrent spontaneous abortion (RSA) has changed over the years, and most societies now advocate defining RSA as two or three consecutive or discontinuous miscarriages with the same sexual partner before 24 weeks gestation In recent years, the incidence of this disease has been on the rise, occurring in about 1%- 5% of pregnancy in women at childbearing age, and the success rate of second pregnancy in RSA females has been significantly reduced The etiology of RSA is extremely complex, including anatomical factors, genetic factors, endocrine factors, infectious and immune factors, and pre-thrombosis etiology. However, the cause of the disease is unclear in half of patients and known as unexplained recurrent spontaneous abortion (URSA)

* MicroRNA (miRNA) is a kind of non-coding single-stranded RNA molecule encoded by endogenous genes with a length of about 22 nucleotides . MiRNA negatively regulates gene expression mainly by binding to the 3 'untranslated region (3' UTR) of target mRNA to degrade the target mRNA or inhibit its translation . In recent years, there have been numerous reports about miRNA's involvement in the pathogenesis of RSA, and many of them have focused on how miRNA regulates trophoblast function. * Additionally, microRNA (miR)-410-5p has been discovered to serve as oncogenes and tumor suppressors altering cell functions in numerous ways including proliferation, apoptosis, biochemistry metabolism, and inflammatory responses in different human malignancies, such as liver cancer, pancreatic cancer, colon cancer, and non-small cell lung cancer. Recent studies showed that miR-410-5p may be involved in the non-cancerous disorder processes such as RSA . Overexpression of miR-410-5p in trophoblast cells inhibited the polarization of M2 macrophages, while knockdown of miR-410-5p was beneficial to recruitment of trophoblast cell and promoted the polarization of M2 macrophages. Furthermore, MicroRNA (miR)-410-5p was discovered to bind with 3'-UTR of ITGA6 . * The adhesion molecule integrin alpha-6 (ITGA6, CD49f), a member of the integrin family, is overexpressed in many cancers and enhances cell movement and signal output . * Down-regulation of ITGA6 changed the biological function of trophoblast cells, inhibited cell proliferation, invasion and migration, and induced apoptosis. ITGA6 may affect the biological functions of trophoblast cells by regulating PI3K/AKT and MAPK signaling pathways. MAPK signaling promote apoptosis through inducing releasing of cytochrome c, which in turn induces further caspase activation (caspase-9 and the effector caspases-3, -6, and -7) . * Baculoviral IAP Repeat Containing 7(BIRC7) encodes the protein Livin which is a member of the inhibitor of apoptosis protein (IAP) family. Livin consists of a single baculoviral IAP repeat domain (BIR) and a RING domian at the C-terminus. The protein inhibits apoptosis by inhibiting proteolytic activation of capsases. * Currently, the interaction of BIRC7 and NK cells in endometrium/decidual remains unknown. BIRC7 in decidua cell may possess the ability to prevent NK cells from killing embryonic and extraembryonic cells, decreased level of BIRC7 and increased number of NK cells in the RM group attribute to the occurrence of miscarriage