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circRNA N6-methyladenosine methylation in preeclampsia and the potential role of N6-methyladenosine-modified circPAPPA2 in trophoblast invasion.
- Source :
-
Scientific reports [Sci Rep] 2021 Dec 21; Vol. 11 (1), pp. 24357. Date of Electronic Publication: 2021 Dec 21. - Publication Year :
- 2021
-
Abstract
- Here, we performed N6-methyladenosine (m6A) RNA sequencing to determine the circRNA m6A methylation changes in the placentas during the pathogenesis of preeclampsia (PE). We verified the expression of the circRNA circPAPPA2 using quantitative reverse transcription-PCR. An invasion assay was carried out to identify the role of circPAPPA2 in the development of PE. Mechanistically, we investigated the cause of the altered m6A modification of circPAPPA2 through overexpression and knockdown cell experiments, RNA immunoprecipitation, fluorescence in situ hybridization and RNA stability experiments. We found that increases in m6A-modified circRNAs are prevalent in PE placentas and that the main changes in methylation occur in the 3'UTR and near the start codon, implicating the involvement of these changes in PE development. We also found that the levels of circPAPPA2 are decreased but that m6A modification is augmented. Furthermore, we discovered that methyltransferase‑like 14 (METTL14) increases the level of circPAPPA2 m6A methylation and that insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) maintains circPAPPA2 stability. Decreases in IGF2BP3 levels lead to declines in circPAPPA2 levels. In summary, we provide a new vision and strategy for the study of PE pathology and report that placental circRNA m6A modification appears to be an important regulatory mechanism.<br /> (© 2021. The Author(s).)
- Subjects :
- Adenosine chemistry
Case-Control Studies
Female
Humans
Methyltransferases genetics
Methyltransferases metabolism
Placenta metabolism
Pre-Eclampsia genetics
Pre-Eclampsia metabolism
Pregnancy
RNA, Circular chemistry
RNA-Binding Proteins genetics
RNA-Binding Proteins metabolism
Trophoblasts metabolism
Adenosine analogs & derivatives
Gene Expression Regulation
Placenta pathology
Pre-Eclampsia pathology
Pregnancy-Associated Plasma Protein-A genetics
RNA, Circular genetics
Trophoblasts pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 34934095
- Full Text :
- https://doi.org/10.1038/s41598-021-03662-5