Emerging role of m6A methylation modification in ovarian cancer

Chang, Ling‐Sai; Xu, Xiaqing; Liu, Xueling; Guo, Qianqian; Fan, Yannan; Zhang, Wenzhou

doi:10.1186/s12935-021-02371-3

Cited by 14 publications

(14 citation statements)

References 166 publications

(308 reference statements)

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“…Abnormal m6A modi cations have been associated with proliferation, drug resistance, and prognosis of ovarian and other cancers [22][23][24]. The global m6A pro le has previously been screened in several cancers, such as endometrioid ovarian cancer [25], invasive malignant pleomorphic adenoma [26], and colorectal cancer [27].…”

Section: Discussionmentioning

confidence: 99%

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Synchronous profiling of mRNA N6-methyladenosine modifications and mRNA expression in high-grade serous ovarian cancer

Yang

Liu

Jin

et al. 2023

Preprint

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Objective To synchronously determine epitranscriptome-wide RNA N6-methyladenosine (m6A) modifications and mRNA expression profile in high grade serous ovarian cancer (HGSOC).Methods The methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to comprehensively examine the m6A modification and the RNA-sequencing (RNA-seq) was performed to analyze the mRNA expression profile in HGSOC and normal fallopian tube (FT) tissues. Go and KEGG analyses were carried out in the enrichment of those differentially methylated and expressed genes.Results MeRIP-seq data showed 53,794 m6A methylated peaks related to 19,938 genes in the HGSOC group and 51,818 m6A peaks representing 19,681 genes in the FT group. RNA-seq results revealed 2,321 upregulated and 2,486 downregulated genes in HGSOC. Conjoint analysis of MeRIP-seq and RNA-seq data identified differentially expressed genes in which 659 were hypermethylated and 897 were hypomethylated. The expression of the m6A eraser (FTO) was significantly lower, but the m6A readers (IGF2BP2 and IGF2BP3) were higher in HGSOC, which was validated by the subsequent real-time PCR assay. Functional enrichment analysis indicated that these differentially modulated genes are involved in pathways related to cancer development.Conclusions For the first time, our study screens the epitranscriptome-wide m6A modification and expression profiles of their modulated genes and signaling pathways in HGSOC. Our findings provide an alternative direction in exploring the molecular mechanisms of ovarian pathogenesis.

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Section: Discussionmentioning

confidence: 99%

“…In this study, we applied MeRIP-seq to investigate the global m6A modi cation and RNA-sequencing (RNA-seq) to determine gene expression pro le in HGSOC and normal fallopian tube (FT) tissues. Our ndings would assist in exploring the molecular mechanism, diagnostic markers, and therapeutic targets for ovarian cancer [22].…”

Section: Introductionmentioning

confidence: 92%

Synchronous profiling of mRNA N6-methyladenosine modifications and mRNA expression in high-grade serous ovarian cancer

Yang

Liu

Jin

et al. 2023

Preprint

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“…The ectopic expression of m6A methylation regulators is involved in OC progression. Specifically, YTHDF1, YTHDF2, IGF2BP1, METTL3, ALKBH5, WTAP, and FZD10 were upregulated, whereas FTO was downregulated [ 58 ]. Taken together, these results suggest that OGN might regulate m6A methylation or ferroptosis to promote OC concurrence, development, and progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis

Zou

Liao

et al. 2022

J Ovarian Res

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Background Accumulating evidence suggests a strong association between polycystic ovary syndrome (PCOS) and ovarian cancer (OC), but the potential molecular mechanism remains unclear. In this study, we identified previously unrecognized genes that are significantly correlated with PCOS and OC via bioinformatics. Materials and methods Multiple bioinformatic analyses, such as differential expression analysis, univariate Cox analysis, functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis, and immune infiltration analysis, were utilized. We further evaluated the effect of OGN on FSHR expression via immunofluorescence. Results TCGA-OC, GSE140082 (for OC) and GSE34526 (for PCOS) datasets were downloaded. Twelve genes, including RNF144B, LPAR3, CRISPLD2, JCHAIN, OR7E14P, IL27RA, PTPRD, STAT1, NR4A1, OGN, GALNT6 and CXCL11, were identified as signature genes. Drug sensitivity analysis showed that OGN might represent a hub gene in the progression of PCOS and OC. Experimental analysis found that OGN could increase FSHR expression, indicating that OGN could regulate the hormonal response in PCOS and OC. Furthermore, correlation analysis indicated that OGN function might be closely related to m6A and ferroptosis. Conclusions Our study identified a 12-gene signature that might be involved in the prognostic significance of OC. Furthermore, the hub gene OGN represent a significant gene involved in OC and PCOS progression by regulating the hormonal response.

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“…Therefore, early detection and effective treatment options for OC are imperative research areas that can significantly improve patient outcomes. Extensive investigations have demonstrated the crucial involvement of Mettl3 in OC pathogenesis, as it significantly promotes the growth and invasion of OC cells through various mechanisms, including modulation of the PI3K/AKT signaling pathway ( Chang et al, 2021 ). Thus, thorough investigations of the molecular mechanisms underlying m6A methylation in ovarian tissues may uncover novel avenues for the diagnosis and treatment of OC.…”

Section: The Role Of Mettl3 In Ovarian Cancermentioning

confidence: 99%

The role of RNA methyltransferase METTL3 in gynecologic cancers: Results and mechanisms

Zhang

2023

Front. Pharmacol.

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N6-methyladenosine (m6A) methylation is the most prevalent mRNA modification in eukaryotes, and it is defined as the methylation of nitrogen atoms on the six adenine (A) bases of RNA in the presence of methyltransferases. Methyltransferase-like 3 (Mettl3), one of the components of m6A methyltransferase, plays a decisive catalytic role in m6A methylation. Recent studies have confirmed that m6A is associated with a wide spectrum of biological processes and it significantly affects disease progression and prognosis of patients with gynecologic tumors, in which the role of Mettl3 cannot be ignored. Mettl3 is involved in numerous pathophysiological functions, such as embryonic development, fat accumulation, and tumor progression. Moreover, Mettl3 may serve as a potential target for treating gynecologic malignancies, thus, it may benefit the patients and prolong survival. However, there is a need to further study the role and mechanism of Mettl3 in gynecologic malignancies. This paper reviews the recent progression on Mettl3 in gynecologic malignancies, hoping to provide a reference for further research.

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Emerging role of m6A methylation modification in ovarian cancer

Cited by 14 publications

References 166 publications

Synchronous profiling of mRNA N6-methyladenosine modifications and mRNA expression in high-grade serous ovarian cancer

Synchronous profiling of mRNA N6-methyladenosine modifications and mRNA expression in high-grade serous ovarian cancer

Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis

The role of RNA methyltransferase METTL3 in gynecologic cancers: Results and mechanisms

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