Role of m6A modification in female infertility and reproductive system diseases

Chen, Jinyu; Fang, Yiwei; Xu, Ying; Sun, Haotong

doi:10.7150/ijbs.69771

Cited by 43 publications

(24 citation statements)

References 99 publications

(118 reference statements)

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“…Reduced FTO expression in the liver, prostate, papillary thyroid, colorectal, and lung adenocarcinoma has been associated with poor prognosis [ 22 , 23 , 24 , 25 , 26 ]. Mechanistically, FTO demethylates downstream target mRNAs, affects m6A levels, and exerts pro- or anti-cancer effects [ 27 , 28 , 29 , 30 , 31 ]. However, due to differences in FTO expression and reader selection, FTO has different impacts on tumorigenesis and progression.…”

Section: Introductionmentioning

confidence: 99%

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

Sun¹,

Zhang²,

Bi³

et al. 2022

Cancers

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Fat mass and obesity-associated protein (FTO) regulates critical pathways in various diseases, including malignant tumours. However, the functional link between FTO and its target genes in epithelial ovarian cancer (EOC) development remains to be elucidated. In this study, the biological functions of FTO were verified in vitro and in vivo. The m6A modification and the binding sites of SNAI1 mRNA were confirmed by m6A RNA immunoprecipitation (MeRIP) and RIP experiments. The actinomycin D assay was used to test the stability of RNA. We found that FTO was downregulated with increased m6A levels in EOC. Reduced expression of FTO was associated with a higher FIGO stage in patients with EOC. Mechanistically, FTO decreased the m6A level and stability of SNAI1 mRNA, causing downregulation of SNAI1 and inhibiting epithelial–mesenchymal transition (EMT). Furthermore, FTO-mediated downregulation of SNAI1 expression depended on IGF2BP2, which acted as an m6A reader binding to the 3′ UTR region of SNAI1 mRNA to promote its stability. In conclusion, FTO inhibits SNAI1 expression to attenuate the growth and metastasis of EOC cells in an m6A-IGF2BP2-dependent manner. Our findings suggest that the FTO-IGF2BP2-SNAI1 axis is a potential therapeutic target in EOC.

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Section: Introductionmentioning

confidence: 99%

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

Sun¹,

Zhang²,

Bi³

et al. 2022

Cancers

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“…Currently, RNA modification has become a new direction for studying embryo development and maternal-fetal immune tolerance. m6A modifications in the endometrium and ovary have been reported to be related to multiple gynecological diseases, including gynecological cancers, adenomyosis, endometriosis, polycystic ovary syndrome and premature ovarian failure, which generally contribute to RPL ( 145 , 146 ). Researchers have proposed that receptivity at the maternal-fetal interface is more reminiscent of cancer immunology ( 35 , 147 ).…”

Section: M6a Functions In Shaping the Local Immune Microenvironmentmentioning

confidence: 99%

The regulation and potential roles of m6A modifications in early embryonic development and immune tolerance at the maternal-fetal interface

Hong

Zheng²,

Liao³

2022

Front. Immunol.

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The immune microenvironment at the maternal-fetal interface was determined by the crosstalk between the trophoblast and maternal-derived cells, which dynamically changed during the whole gestation. Trophoblasts act as innate immune cells and dialogue with maternal-derived cells to ensure early embryonic development, depending on the local immune microenvironment. Therefore, dysfunctions in trophoblasts and maternal decidual cells contribute to pregnancy complications, especially recurrent pregnancy loss in early pregnancy. Since many unknown regulatory factors still affect the complex immune status, exploring new potential aspects that could influence early pregnancy is essential. RNA methylation plays an important role in contributing to the transcriptional regulation of various cells. Sufficient studies have shown the crucial roles of N6-methyladenosine (m6A)- and m6A-associated- regulators in embryogenesis during implantation. They are also essential in regulating innate and adaptive immune cells and the immune response and shaping the local and systemic immune microenvironment. However, the function of m6A modifications at the maternal-fetal interface still lacks wide research. This review highlights the critical functions of m6A in early embryonic development, summarizes the reported research on m6A in regulating immune cells and tumor immune microenvironment, and identifies the potential value of m6A modifications in shaping trophoblasts, decidual immune cells, and the microenvironment at the maternal-fetal interface. The m6A modifications are more likely to contribute to embryogenesis, placentation and shape the immune microenvironment at the maternal-fetal interface. Uncovering these crucial regulatory mechanisms could provide novel therapeutic targets for RNA methylation in early pregnancy.

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“…However, ALKBH5 can directly reduce m6A to original adenylate ( Kumari et al, 2022 ; Song et al, 2022 ). The difference between FTO and ALKBH5 in the metabolic mechanism of m6A results in different biological functions ( Chen J. et al, 2022 ). Recently, ALKBH3 has been suggested to be a novel demethylase protein which mediates the demethylation of m6A, m1A and 3-methylcytidine (m3C) on tRNA ( Liu et al, 2021 ).…”

Section: Abnormal Expression Of N6-methyladenosine Modification Prote...mentioning

confidence: 99%

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

Tian

Mao

Zhang

2022

Front. Cell. Neurosci.

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Central nervous system (CNS) injuries, including traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and ischemic stroke, are the most common cause of death and disability around the world. As the most common modification on ribonucleic acids (RNAs), N6-methyladenosine (m6A) modification has recently attracted great attentions due to its functions in determining the fate of RNAs through changes in splicing, translation, degradation and stability. A large number of studies have suggested that m6A modification played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that m6A modification could improve neurological impairment, inhibit apoptosis, suppress inflammation, reduce pyroptosis and attenuate ferroptosis in CNS injuries via different molecules including phosphatase and tensin homolog (PTEN), NLR family pyrin domain containing 3 (NLRP3), B-cell lymphoma 2 (Bcl-2), glutathione peroxidase 4 (GPX4), and long non-coding RNA (lncRNA). Therefore, m6A modification showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the role of m6A modification in CNS injuries. Hence, on the basis of these properties and effects, m6A modification may be developed as therapeutic agents for CNS injury patients.

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Role of m6A modification in female infertility and reproductive system diseases

Cited by 43 publications

References 99 publications

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

The regulation and potential roles of m6A modifications in early embryonic development and immune tolerance at the maternal-fetal interface

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

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