circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion

Abstract

Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were detected in human pre-implantation embryos, indicating that circRNAs potentially have important regulatory functions. However, the roles of circRNAs in URSA remain largely unknown. In this study, we elucidated deregulated circRNA expression and distinct competing endogenous RNA (ceRNA) networks by comparing URSA placental villus with that of patients with normal pregnancy using microarrays. We characterized a distinct circRNA, circRNA-0050703, which is downregulated in URSA placental villus (thus we named it circRNA-DURSA). Silencing of circRNA-DURSA results in trophoblast cell apoptosis in vitro. Furthermore, mechanistic dissection revealed that circRNA-DURSA exerts its effects by competitively binding to miR-760, which post-transcriptionally targets HIST1H2BE. Additionally, after circRNA-DURSA silencing in vivo, the numbers of implanted embryos decreased significantly. These results reveal the regulatory roles of circRNA-DURSA in trophoblasts and identified a distinct circRNA-DURSA/miR-760/ HIST1H2BE axis as potentially important diagnostic and therapeutic targets for URSA treatment.

Immune Dysfunction Mediated by the ceRNA Regulatory Network in Human Placenta Tissue of Intrahepatic Cholestasis Pregnancy

“…In polycystic ovary syndrome (PCOS), lncRNA MALAT1 reduction could suppress TGFb signaling through sponging miR-125b and miR-203a in granulosa cells (41). In unexplained recurrent spontaneous abortion, circRNA-DURSA/ miR-760/HIST1H2BE axis, lncRNA-HZ04/miR-hz04/BPDE axis, and lncHZ05/miR-hz05/BPDE axis were proved to affect human trophoblast cell proliferation and apoptosis (42)(43)(44). In preeclampsia, lnc00511 was functioned as a molecular sponge for miR-29b-3p, antagonizing its ability to repress Cyr61 protein translation (45).…”

circEPSTI1 promotes tumor progression and cisplatin resistance via upregulating MSH2 in cervical cancer

“…Overwhelming evidence illustrates that circRNAs have pivotal roles in the onset and progress of various disease, including cancer [ 23 ], dilated cardiomyopathy [ 24 ], heart failure [ 25 ], and unexplained recurrent spontaneous abortion [ 26 ]. CircRNAs can modulate the expression of many key genes via diverse mechanisms, consisting of cross talking with miRNAs, binding proteins, and encoding small molecule polypeptides [ 27 ].…”

Expression Profiling of Circular RNAs in Early Pregnant Jianghuai Buffaloes

“…Some studies have found that changes in circRNA expression patterns are also observed in the endometrium of patients with recurrent miscarriages. Zhu [ 44 ] reported that circRNA-DURSA regulates the apoptosis of embryonic trophectoderm cells in recurrent spontaneous abortion via the miRNA-760-HIST1H2BE axis. This suggests that specific circRNAs are likely to be candidate biomarkers or molecular targets for unexplained recurrent spontaneous abortion.…”