Circular RNA hsa_circ_0026552 inhibits the proliferation, migration and invasion of trophoblast cells via the miR‑331‑3p/TGF‑βR1 axis in pre‑eclampsia

Abstract

Globally, pre-eclampsia (PE) is a gestational disorder that causes increased morbidity of the fetus and mortality induced by pregnancy. Despite various studies, the understanding of the causes or mechanism of the development of PE remains elusive. Thus, the present study aimed to investigate the role of circular (circ)RNA hsa_circ_0026552 (hsa_circ_0026552) in the development of PE and its mechanism of regulation. hsa_circ_0026552 differential expression in PE tissue data and clinical samples were analyzed and it was observed that hsa_circ_0026552 is highly upregulated in PE samples. Furthermore, miR-331-3p was detected as an hsa_circ_0026552 target miRNA and TGF-βR1 gene as a target of miR-331-3p. These results were confirmed using various assays, including dual-luciferase reporter, reverse transcription-quantitative PCR and RNA pull-down assay. It was observed that miR-331-3p expression was negatively correlated to hsa_circ_0026552 relative expression, while TGF-βR1 expression was positively correlated to hsa_circ_0026552 expression evaluated by Pearson's correlation test. The functional experiments, including Cell Counting Kit-8, colony formation and Transwell assay, showed that silencing hsa_circ_0026552 could significantly strengthen the proliferation, migration and invasion of the trophoblastic HTR-8/SVneo cells, but the subsequent overexpression of hsa_circ_0026552 reversed this. Mechanistically, it was concluded that hsa_circ_0026552 acts as a miR-331-3p sponge to upregulate TGF-βR1 expression in trophoblasts and is involved significantly in PE development and progression in pregnant women. The circRNA hsa_circ_0026552 could be a novel therapeutic target and prognostic biomarker for PE.

N6‐methyladenosine modification in trophoblasts promotes circSETD2 expression, inhibits miR‐181a‐5p, and elevates MCL1 transcription to reduce apoptosis of trophoblasts

“…CircRNAs are more abundant and specific compared with other RNAs and researchers have suggested that circRNAs could be strong biomarkers for PE 24 . For example, elevated circRNA hsa_circ_0008726 and hsa_circ_0026552 in PE placenta tissues could be potential biomarkers and therapeutic targets for PE 25,26 . Our results elicited that circSETD2 expression was both under‐expressed in chorionic trophoblasts of PE rats and PE HTR8/SVneo cells.…”

“…24 For example, elevated circRNA hsa_circ_0008726 and hsa_circ_0026552 in PE placenta tissues could be potential biomarkers and therapeutic targets for PE. 25,26 Our results elicited that circSETD2 expression was both under-expressed in chorionic trophoblasts of PE rats and PE HTR8/SVneo cells. PE is associated with extensive apoptosis of trophoblast cells invading the uterus.…”

Circular RNAs in the Origin of Developmental Lung Disease: Promising Diagnostic and Therapeutic Biomarkers

“…Remarkedly, the GEO databases GSE102897 and GSE96985 show different expression profiles of circRNAs in human preeclampsia and normal placentas. It has been shown that increased circRNAs such as circ_0001687, circLRRK1, circ_0008726, circ_0085296, circ_0011460, circ_0026552 and decreased circRNAs such as circ_0001513 play a role in trophoblast proliferation, migration, and angiogenesis during preeclampsia development [ 83 , 84 , 85 , 86 , 87 , 88 ].…”

Circ_0001861 facilitates trophoblast cell proliferation, migration, invasion and epithelial-mesenchymal transition via the miR-296-5p/forkhead box protein 1 pathway in preeclampsia

“…Growing evidence suggested that circRNAs functioned as miRNA sponges in PE progression [17,18]. We analyzed the location of circ_0001861 in trophoblast cells.…”