Expression Profile of New Gene Markers and Signaling Pathways Involved in Immunological Processes in Human Cumulus-Oophorus Cells

Chermuła, Błażej; Hutchings, Greg; Kranc, Wiesława; Józkowiak, Małgorzata; Jopek, Karol; Stelmach, Boguslawa A.; Mozdziak, Paul; Pawełczyk, Leszek; Piotrowska‐Kempisty, Hanna; Spaczyński, Robert; Kempisty, Bartosz

doi:10.3390/genes12091369

Cited by 3 publications

(3 citation statements)

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“…However, TUBA1B, a critical gene in postmenopausal osteoporosis, has also been linked to BMI in children's muscles and the overall survival of colorectal cancer patients (39)(40)(41). The expression level of MX1 in cumulus-oophorus cells was related to the immunological defense processes (42). Regarding the 3′UTR RNA editing, NUP43:chr6:149725375, PHLDA1:chr12:76027474, and RBBP4:chr1:32680141 were the top three significant editing sites.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS

Kong

Zhou

et al. 2023

Front. Endocrinol.

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BackgroundPolycystic ovary syndrome (PCOS) is a complex, multifactor disorder in women of reproductive age worldwide. Although RNA editing may contribute to a variety of diseases, its role in PCOS remains unclear.MethodsA discovery RNA-Seq dataset was obtained from the NCBI Gene Expression Omnibus database of granulosa cells from women with PCOS and women without PCOS (controls). A validation RNA-Seq dataset downloaded from the European Nucleotide Archive Databank was used to validate differential editing. Transcriptome-wide investigation was conducted to analyze adenosine-to-inosine (A-to-I) RNA editing in PCOS and control samples.ResultsA total of 17,395 high-confidence A-to-I RNA editing sites were identified in 3,644 genes in all GC samples. As for differential RNA editing, there were 545 differential RNA editing (DRE) sites in 259 genes with Nucleoporin 43 (NUP43), Retinoblastoma Binding Protein 4 (RBBP4), and leckstrin homology-like domain family A member 1 (PHLDA) showing the most significant three 3′-untranslated region (3′UTR) editing. Furthermore, we identified 20 DRE sites that demonstrated a significant correlation between editing levels and gene expression levels. Notably, MIR193b-365a Host Gene (MIR193BHG) and Hook Microtubule Tethering Protein 3 (HOOK3) exhibited significant differential expression between PCOS and controls. Functional enrichment analysis showed that these 259 differentially edited genes were mainly related to apoptosis and necroptosis pathways. RNA binding protein (RBP) analysis revealed that RNA Binding Motif Protein 45 (RBM45) was predicted as the most frequent RBP binding with RNA editing sites. Additionally, we observed a correlation between editing levels of differential editing sites and the expression level of the RNA editing enzyme Adenosine Deaminase RNA Specific B1 (ADARB1). Moreover, the existence of 55 common differentially edited genes and nine differential editing sites were confirmed in the validation dataset.ConclusionOur current study highlighted the potential role of RNA editing in the pathophysiology of PCOS as an epigenetic process. These findings could provide valuable insights into the development of more targeted and effective treatment options for PCOS.

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Section: Discussionmentioning

confidence: 99%

Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS

Kong

Zhou

et al. 2023

Front. Endocrinol.

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“…Pathwayfold enrichment for six transcripts (i.e., KRT8, KRT18, DSG, PDGFRA, AKAP12 and CSRP3) stood apart from the rest (Supplementary Table 2). The first five of these six transcripts are known to be expressed within the ovarian follicle and are linked to cell proliferation and apoptosis (108)(109)(110)(111). Their downregulation, therefore, could tentatively be associated with more 'viable' and 'mature' COCs.…”

Section: Melatonin and Complex Proteins Interact During Ivm To Impact...mentioning

confidence: 99%

Developmental, cytogenetic and epigenetic consequences of removing complex proteins and adding melatonin during in vitro maturation of bovine oocytes

Tutt,

Guven-Ates,

Kwong

et al. 2023

Front. Endocrinol.

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BackgroundIn vitro maturation (IVM) of germinal vesicle intact oocytes prior to in vitro fertilization (IVF) is practiced widely in animals. In human assisted reproduction it is generally reserved for fertility preservation or where ovarian stimulation is contraindicated. Standard practice incorporates complex proteins (CP), in the form of serum and/or albumin, into IVM media to mimic the ovarian follicle environment. However, the undefined nature of CP, together with batch variation and ethical concerns regarding their origin, necessitate the development of more defined formulations. A known component of follicular fluid, melatonin, has multifaceted roles including that of a metabolic regulator and antioxidant. In certain circumstances it can enhance oocyte maturation. At this stage in development, the germinal-vesicle intact oocyte is prone to aneuploidy and epigenetic dysregulation.ObjectivesTo determine the developmental, cytogenetic and epigenetic consequences of removing CP and including melatonin during bovine IVM.Materials and methodsThe study comprised a 2 x 2 factorial arrangement comparing (i) the inclusion or exclusion of CP, and (ii) the addition (100 nM) or omission of melatonin, during IVM. Cumulus-oocyte complexes (COCs) were retrieved from stimulated cycles. Following IVM and IVF, putative zygotes were cultured to Day 8 in standard media. RNAseq was performed on isolated cumulus cells, cytogenetic analyses (SNP-based algorithms) on isolated trophectoderm cells, and DNA methylation analysis (reduced representation bisulfite sequencing) on isolated cells of the inner-cell mass.ResultsRemoval of CP during IVM led to modest reductions in blastocyst development, whilst added melatonin was beneficial in the presence but detrimental in the absence of CP. The composition of IVM media did not affect the nature or incidence of chromosomal abnormalities but cumulus-cell transcript expression indicated altered metabolism (primarily lipid) in COCs. These effects preceded the establishment of distinct metabolic and epigenetic signatures several days later in expanded and hatching blastocysts.ConclusionsThese findings highlight the importance of lipid, particularly sterol, metabolism by the COC during IVM. They lay the foundation for future studies that seek to develop chemically defined systems of IVM for the generation of transferrable embryos that are both cytogenetically and epigenetically normal.

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“…ANXA3 is a member of the annexin family of proteins and has 36-kDa and 33-kDa isoforms and closely related calcium (Ca 2+ )- and lipid-binding proteins. These are found at various intra- and extracellular locations, including human cumulus oophorus cells ( 11 ), and interact with a broad range of membrane lipids and proteins. Upregulation of ANXA3 expression in tumor tissues has been found to be closely associated with cell proliferation, migration, and apoptosis ( 12 ) via the phosphatidylinositol-3 kinase/protein kinase B ( 13 ), nuclear factor-κB ( 14 ), c-Jun ( 15 ), extracellular signal-regulated kinase, and hypoxia-inducible factor-1 signaling ( 16 ) pathways.…”

Section: Introductionmentioning

confidence: 99%

High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses

Li¹,

Lin²,

Abdelrahman³

2022

Ann Transl Med

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Expression Profile of New Gene Markers and Signaling Pathways Involved in Immunological Processes in Human Cumulus-Oophorus Cells

Cited by 3 publications

References 53 publications

Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS

Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS

Developmental, cytogenetic and epigenetic consequences of removing complex proteins and adding melatonin during in vitro maturation of bovine oocytes

High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses

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