Identification of circular RNAs as regulators and noninvasive biomarkers for placenta accreta spectrum

in Reproduction
Authors:
Junfang ShiDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

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Mengtian YangDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

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Xin CaoDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

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Qitao HuangDepartment of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, Guangdong, China
Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China

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Fang HeDepartment of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Engineering and Technology Research Center of Maternal-Fetal Medicine, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

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You PengDivision of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China

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Jinru CuiDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

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Wenqian ChenDivision of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China

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Yiming XuDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

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Wenyan GengDepartment of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Engineering and Technology Research Center of Maternal-Fetal Medicine, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

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Laixin XiaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

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Dunjin ChenDepartment of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Engineering and Technology Research Center of Maternal-Fetal Medicine, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

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Shan XiaoDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

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https://orcid.org/0000-0002-4012-7650
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Correspondence should be addressed to S Xiao or D Chen or L Xia; Email: asdfg@smu.edu.cn or gzdrchen@gzhmc.edu.cn or xialx@smu.edu.cn

*(J Shi, M Yang, X Cao and Q Huang contributed equally to this work)

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In brief

Placenta accreta spectrum (PAS) has an urgent need for reliable prenatal biomarkers. This study profiled the circular RNAs (circRNAs) in PAS placenta and maternal blood and identified two circRNAs can regulate trophoblast cells invasion and serve as noninvasive prenatal biomarkers for PAS prediction.

Abstract

PAS is one of the most alarming obstetric diseases with high mortality rates. The regulating mechanism underlying PAS remains to be investigated, and reliable blood biomarkers for PAS have not emerged. Circular RNAs (circRNAs) have become important regulators and biomarkers for disparate human diseases. However, the circRNA profiles of PAS were not reported, and the regulatory role and predictive value of circRNAs in PAS were unknown. Here, we comprehensively profiled the circRNAs in the placenta of PAS by transcriptome sequencing and analysis and uncovered 217 abnormally expressed circRNAs. Through competing endogenous RNA network analysis, we found that the target genes of upregulated circRNAs in PAS were enriched in placenta development-related pathways and further uncovered two circRNAs, circPHACTR4 and circZMYM4, that could regulate trophoblast cells invasion and migration in vitro. Finally, we verified that circPHACTR4 and circZMYM4 were also upregulated in the maternal peripheral blood of PAS women before delivery using transcriptome sequencing and RT-qPCR and evaluated their predictive value by ROC curves. We found that circPHACTR4 and circZMYM4 could serve as effective predicting biomarkers for PAS (area under the curve (AUC): 0.86 and 0.85) and propose an improved model for PAS prenatal prediction by combining the conventional ultrasound diagnosis with the new circRNA predictive factors (AUC: 0.91, specificity: 0.89, sensitivity: 0.82).Altogether, this work provides new resources for deciphering the biological roles of circRNAs in PAS, identified two circRNAs that could regulate trophoblast cells invasion during placentation, and revealed two noninvasive diagnostic markers for PAS.

 

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