Regulation And Expression Of The Circular RNA In Decidualization

Implantation is a dynamic and highly coordinated process accompanied by the differential and overlapping expression of many genes.With the interaction between active blastocyst and receptive uterus,successful implantation is accomplished by the process of apposition,adhesion and penetration.After implantation,the embryo gradually invades into the endometrium.In order to maintain healthy growth of embryo,stromal cells proliferate and differentiate extensively,which is named decidualization.In the 1970 s,RNA with ring structure has already been found.However,this circular RNA has not been explored for long time.Until recently,with the development of high-throughput sequencing and bioinformatics technologies,circular RNA attracts people's attentions again.Unlike conventional linear RNAs(including 5'and 3' ends),the structure of circular RNA molecules is blocked,which means it cannot be degraded easily by exonuclease RNaseR and is more stable than linear RNA.The circular RNA is ubiquitous in eukaryotes with high cell-specificity and conservation.It is widely existed in human cells,even exceeding 10 times of their linear isomers.Many studies have found that a variety of RNA-binding proteins(RBP)can be combined with the circular RNA to form RNA-protein complex(RPC)and regulate the formation of circular RNA.Among them,Muscleblind(MBL or MBNL1)involves in the regulation of loop RNA synthesis by forming a "bridge" between intron pairs.The circular RNA has a variety of functions,and studies have reported the role of circular RNA in recurrent miscarriage and endometrial cancer,suggested that the circular RNA has a certain role in the uterus,but its function in implantation and decidualization has not been reported yet.In this study,we detected the expression of MBNL1 and MBNL2 in vitro and in vitro decidualization models,suggesting that MBNL1 and MBNL2 are associated with decidualization.MBNL1 and MBNL2 were specifically expressed in the decidual region on days 5 and 8 of pregnancy,indicating that MBNL may regulate decidualization by regulating RNA generation;furthermore,this experiment determined the expression and distribution of the circular RNA during decidualization through circular RNA sequencing and idnetified many the circular RNAs that change dramatically during decidualization.The confirmation of ciSKIL2 and ciLPAP1 expression in decidualization suggests that the circular RNA is related with decidualization and that circular RNA expression profile would be a marker for decidualization.In summary,our results suggest the potential role of circular RNA during of the process of decidualization,MBNL1 and MBNL2 may be involved in the formation of the circular RNA.Our study provides a new perspective for the study of implantation mechanism and identifies a previously unknown singling pathway during decidualization.The results may serve as theoretical basis for clinical applications and therapeutic strategies.