IMR Press / FBL / Volume 28 / Issue 11 / DOI: 10.31083/j.fbl2811314
Open Access Original Research
Unveiling Circular RNA-Mediated Regulatory Mechanisms in Necroptosis in Premature Ovarian Failure
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1 Department of Tuina, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006 Hangzhou, Zhejiang, China
2 School of Nursing, Hangzhou Medical College, 311399 Hangzhou, Zhejiang, China
3 Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006 Hangzhou, Zhejiang, China
4 Department of Lung Disease, Jining Hospital of Traditional Chinese Medicine, 272037 Jining, Shandong, China
5 Center of Reproductive Medicine, The Second Hospital Affiliated to Shandong University of Traditional Chinese Medicine, 250001 Jinan, Shandong, China
*Correspondence: 20163354@zcmu.edu.cn (Wenjun Chen)
Front. Biosci. (Landmark Ed) 2023, 28(11), 314; https://doi.org/10.31083/j.fbl2811314
Submitted: 24 February 2023 | Revised: 15 June 2023 | Accepted: 7 July 2023 | Published: 28 November 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Necroptosis is a programmed necrotic cell death, in which dying cells rupture and release intracellular components that trigger a proinflammatory response. The current study aimed at probing the circular RNA (circRNA)-mediated regulatory mechanisms in necroptosis in premature ovarian failure (POF). Methods: CircRNA sequencing analysis was conducted in ovarian tissues of control and POF rats and transcriptome microarrays were acquired from the GSE33423 dataset. Differential expression analysis of circRNAs and mRNAs was executed between the POF and control data. Both a necroptosis-based circRNA–microRNA (miRNA)–mRNA network and a protein–protein interaction (PPI) network were established. Then, the functional annotation and immunological traits were analyzed. Results: Totally, 1266 upregulated and 1283 downregulated circRNAs as well as 1101 upregulated and 1168 downregulated mRNAs were determined in the POF rats versus the controls. The differentially expressed mRNAs predominantly correlated with necroptosis. The circRNA–miRNA–mRNA networks of downregulated necroptosis genes (comprising rno_circRNA_004995-rno-miR-148b-5p-H2afy2, rno_circRNA_016998-rno-miR-29a-5p-Hmgb1, and rno_circRNA_017593-rno-miR-29a-5p-Hmgb1) and upregulated necroptosis genes (comprising rno_circRNA_015900-rno-miR-935-Stat1, rno_circRNA_007946-rno-miR-328a-3p-Stat5a, rno_circRNA_007947-rno-miR-328a-3p-Stat5a, rno_circRNA_005064-rno-miR-18a-5p-Stat1, rno_circRNA_005064-rno-miR-18a-5p-Stat5a, rno_circRNA_005115-rno-miR-22-3p-Stat1, rno_circRNA_009028-rno-miR-342-5p-Stat1, rno_circRNA_011240-rno-miR-1224-Stat5a, rno_circRNA_016078-rno-miR-711-Stat5a) were built. POF-specific necroptosis genes (STAT1, STAT5A, PLA2G4A, HMG1L1, HMGB1, AGER, EGFR, HDAC7, IFNA1, IL10RB, IL27RA, PYGL, SOCS1, TRADD, CXCL10, DDX5, EZH2, FADS2, FER, H2AFY2, HIST1H2AF, IFI44L, IL27, IRGM, MX1, NFKB2, PAFAH2, PEMT, PGM2L1, PGR, PHKA2, and PLB1) were selected since they displayed notable associations with most immune cells, immune checkpoints, chemokines, human leukocyte antigen (HLA) molecules, and immune receptors. Conclusions: Altogether, we proposed the presence of widespread regulatory mechanisms of circRNAs in necroptosis and demonstrated that altered circRNA biogenesis might contribute to POF by affecting necroptosis.

Keywords
premature ovarian failure
circRNA
necroptosis
circRNA–miRNA–mRNA network
protein–protein interaction
immunity
Funding
82004405/National Natural Science Foundation of China
LQ20H270005/Exploration Project of Natural Science Foundation of Zhejiang Province
2023ZL366/Zhejiang Province Traditional Chinese Medicine Science and technology Project
Figures
Fig. 1.
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