PMID- 38062819 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240220 IS - 2768-6698 (Electronic) IS - 2768-6698 (Linking) VI - 28 IP - 11 DP - 2023 Nov 28 TI - Unveiling Circular RNA-Mediated Regulatory Mechanisms in Necroptosis in Premature Ovarian Failure. PG - 314 LID - 10.31083/j.fbl2811314 [doi] AB - 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. CI - (c) 2023 The Author(s). Published by IMR Press. FAU - Jin, Xin AU - Jin X AD - Department of Tuina, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006 Hangzhou, Zhejiang, China. FAU - Chen, Wenjun AU - Chen W AD - School of Nursing, Hangzhou Medical College, 311399 Hangzhou, Zhejiang, China. AD - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006 Hangzhou, Zhejiang, China. FAU - Wang, Jiaxi AU - Wang J AD - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006 Hangzhou, Zhejiang, China. FAU - Xu, Xianli AU - Xu X AD - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006 Hangzhou, Zhejiang, China. FAU - Zhang, Ting AU - Zhang T AD - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006 Hangzhou, Zhejiang, China. FAU - Wang, Lu AU - Wang L AD - Department of Lung Disease, Jining Hospital of Traditional Chinese Medicine, 272037 Jining, Shandong, China. FAU - Feng, Xuehua AU - Feng X AD - Center of Reproductive Medicine, The Second Hospital Affiliated to Shandong University of Traditional Chinese Medicine, 250001 Jinan, Shandong, China. LA - eng GR - 82004405/National Natural Science Foundation of China/ GR - LQ20H270005/Exploration Project of Natural Science Foundation of Zhejiang Province/ GR - 2023ZL366/Zhejiang Province Traditional Chinese Medicine Science and technology Project/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Singapore TA - Front Biosci (Landmark Ed) JT - Frontiers in bioscience (Landmark edition) JID - 101612996 RN - 0 (RNA, Circular) RN - 0 (HMGB1 Protein) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - EC 2.7.1.19 (PHKA2 protein, human) RN - EC 2.7.1.19 (Phosphorylase Kinase) RN - 0 (MIRN1224 microRNA, human) RN - 0 (MIRN711 microRNA, rat) SB - IM MH - Female MH - Humans MH - Rats MH - Animals MH - RNA, Circular/genetics MH - *HMGB1 Protein MH - *Primary Ovarian Insufficiency/genetics MH - Necroptosis/genetics MH - *MicroRNAs/genetics/metabolism MH - RNA, Messenger/genetics MH - Phosphorylase Kinase OTO - NOTNLM OT - circRNA OT - circRNA-miRNA-mRNA network OT - immunity OT - necroptosis OT - premature ovarian failure OT - protein-protein interaction COIS- The authors declare no conflict of interest. EDAT- 2023/12/08 06:42 MHDA- 2023/12/17 13:19 CRDT- 2023/12/08 03:42 PHST- 2023/02/24 00:00 [received] PHST- 2023/06/15 00:00 [revised] PHST- 2023/07/07 00:00 [accepted] PHST- 2023/12/17 13:19 [medline] PHST- 2023/12/08 06:42 [pubmed] PHST- 2023/12/08 03:42 [entrez] AID - S2768-6701(23)00956-5 [pii] AID - 10.31083/j.fbl2811314 [doi] PST - ppublish SO - Front Biosci (Landmark Ed). 2023 Nov 28;28(11):314. doi: 10.31083/j.fbl2811314.