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Published on: January 30, 2017
Competing endogenous RNA expression profiling in pre-eclampsia identifies hsa_circ_0036877 as a potential novel blood
Xiaopeng Hu1,2,3, Junping Ao4, Xinyue Li2
11International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, No. 910. Hengshan Road, Xuhui District, Shanghai, 200030 China.
Insights
This study identifies novel circular RNAs (circRNAs) as potential biomarkers for predicting pre-eclampsia (PE). Researchers discovered specific circRNAs in placental tissue and validated one, hsa_circ_0036877, as a promising blood biomarker for early PE detection.
Area of Science:
- Reproductive biology
- Molecular pathology
- Biomarker discovery
Background:
- The exact causes and mechanisms of pre-eclampsia (PE) remain unknown, and effective early diagnostic markers are lacking.
- The competing endogenous RNA (ceRNA) hypothesis offers a novel framework for investigating PE's molecular underpinnings.
- Circular RNAs (circRNAs), known for their structural stability, are explored as potential biomarkers.
Purpose of the Study:
- To profile messenger RNA, long non-coding RNA, and circRNA expression in normal and severe pre-eclampsia (SPE) placentas.
- To identify differentially expressed circRNAs in PE placentas for potential use as early clinical biomarkers in blood.
- To investigate the role of circRNAs within the ceRNA network in PE pathogenesis.
Main Methods:
- Microarray analysis was employed to compare ceRNA expression profiles in normal versus SPE placentas.
- Bioinformatic analyses, including gene ontology and KEGG pathway analysis, were used to interpret microarray data and construct ceRNA networks.
- Quantitative real-time PCR (qRT-PCR) and RNA immunoprecipitation (RIP) were utilized for validation of specific circRNAs and their ceRNA function.
Main Results:
- Microarray analysis identified differentially expressed ceRNAs between normal and SPE placentas.
- Several RNAs, including specific circRNAs (e.g., hsa_circ_0036877) and long non-coding RNAs, were validated using qRT-PCR.
- hsa_circ_0036877 was confirmed to function as a ceRNA and showed potential as a novel blood biomarker for early PE detection.
Conclusions:
- This study presents the first systematic profiling of ceRNAs in PE placentas, revealing the integrated ceRNA network in the condition.
- The circRNA hsa_circ_0036877 demonstrates potential as a novel biomarker for the early detection of pre-eclampsia.
- These findings contribute to understanding PE's molecular mechanisms and offer a promising avenue for developing early diagnostic tools.
Background:
The etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE. The competing endogenous RNA (ceRNA) hypothesis is a new approach to uncover the molecular pathology of PE. The first aim of this study was to perform messenger RNA, long non-coding RNA, and circular RNA (circRNA) expression profiling of human normal and severe pre-eclampsia (SPE) placentas. circRNA, which has a stable structure, is a more suitable biomarker than other types of RNA. Therefore, the second aim of our study was to select some differentially expressed circRNAs in PE placentas as early clinical biomarkers of PE in blood circulation.
Results:
Using microarray analysis, we investigated differentially expressed ceRNAs in human normal and SPE placentas. Bioinformatics, such as gene ontology, KEGG pathway, and ceRNA network analyses, were performed to evaluate the microarray data and gain further insights into the biological processes. RNAs (Chd5, Furin, lnc-ELAVL4-9:1, lnc-RAP1GAP2-5:2, hsa_circ_0036877, hsa_circ_0036878, hsa_circ_0055724, hsa_circ_0049730, and hsa_circ_0036474) were validated by quantitative real-time PCR (qRT-PCR). RNA immunoprecipitation (RIP) of AGO2 in htra-8 cells and qRT-PCR analysis of hsa_circ_0036877 expression in maternal whole peripheral blood samples of participants were then conducted to confirm that hsa_circ_0036877 is a ceRNA and potential novel blood biomarker for early PE, respectively.
Conclusion:
Our study is the first systematic profiling of ceRNAs in placentas of PE patients and revealed the global ceRNA network integration in PE. Moreover, hsa_circ_0036877 can function as a ceRNA and serve as a potential novel blood biomarker for early PE.
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