Decreased expression of m6A demethylase FTO in ovarian aging

Sun, Xiaoyan; Zhang, Yigan; Hu, Yuping; An, Jun‐Xia; Li, Lifei; Wang, Yiqing; Zhang, Xuehong

doi:10.1007/s00404-020-05895-7

Cited by 24 publications

(23 citation statements)

References 26 publications

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“…Sun et al found that FTO expression levels differed between age groups, with the elderly group showing lower levels of FTO expression than the younger group. At the same time, they investigated the relationship between FTO and ovarian function and found that FTO decreased and m6A increased in the group with reduced ovarian reserve function, which was consistent with the trend of decreasing FTO levels in the older group [126]. Therefore, FTO is not only a tumour suppressor but also a potential indicator of ovarian function.…”

Section: Fto (Fat Mass and Obesity-associated Protein) In Ocmentioning

confidence: 55%

RNA m6A methylation regulators in ovarian cancer

et al. 2021

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N6-methyladenosine (m6A) is the most abundant RNA modification of mammalian mRNAs and plays a vital role in many diseases, especially tumours. In recent years, m6A has become the topic of intense discussion in epigenetics. M6A modification is dynamically regulated by methyltransferases, demethylases and RNA-binding proteins. Ovarian cancer (OC) is a common but highly fatal malignancy in female. Increasing evidence shows that changes in m6A levels and the dysregulation of m6A regulators are associated with the occurrence, development or prognosis of OC. In this review, the latest studies on m6A and its regulators in OC have been summarized, and we focus on the key role of m6A modification in the development and progression of OC. Additionally, we also discuss the potential use of m6A modification and its regulators in the diagnosis and treatment of OC.

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Section: Fto (Fat Mass and Obesity-associated Protein) In Ocmentioning

confidence: 55%

RNA m6A methylation regulators in ovarian cancer

et al. 2021

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“…Next, we identified that CTX raised the m 6 A and methyltransferase levels and inhibited the expression of demethylases and effectors with concentration-dependent ( Huang B. et al, 2019 ). We also found that the expression of FTO reduced and m 6 A content was increased ( Sun et al, 2021 ). Li team further verified that the downregulation of FTO increased m 6 A modification of FOS-mRNA-3′UTR and upregulated the expression of FOS in GCs, eventually resulting in the ovarian aging ( Jiang et al, 2021 ).…”

Section: M 6 a Modification Contributes To Ovarian...mentioning

confidence: 83%

“…However, most of them mainly focused on methyltransferase, such as METTL3/METTL14 ( Zhang J. et al, 2020 ; Wu et al, 2020 ; Liu et al, 2021 ; Chen et al, 2022 ), and the demethylases and readers were gradually concerned in recent years, including ALKBH5 ( Li et al, 2022a ), WTAP ( Li et al, 2022b ), IGF2BP2 ( Deng et al, 2021 ). Notedly, in reproductive aging, FTO has been shown to play the regulatory role ( Ding et al, 2018 ; Zhou L. et al, 2021 ; Jiang et al, 2021 ; Sun et al, 2021 ). Meanwhile, m 6 A modification-related key downstream or upstream proteins have not been deeply studied.…”

Section: M 6 a Methylation Modification In Female ...mentioning

confidence: 99%

The Role of m6A on Female Reproduction and Fertility: From Gonad Development to Ovarian Aging

Sun

et al. 2022

Front. Cell Dev. Biol.

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The growth and maturation of oocyte is accompanied by the accumulation of abundant RNAs and posttranscriptional regulation. N6-methyladenosine (m6A) is the most prevalent epigenetic modification in mRNA, and precisely regulates the RNA metabolism as well as gene expression in diverse physiological processes. Recent studies showed that m6A modification and regulators were essential for the process of ovarian development and its aberrant manifestation could result in ovarian aging. Moreover, the specific deficiency of m6A regulators caused oocyte maturation disorder and female infertility with defective meiotic initiation, subsequently the oocyte failed to undergo germinal vesicle breakdown and consequently lost the ability to resume meiosis by disrupting spindle organization as well as chromosome alignment. Accumulating evidence showed that dysregulated m6A modification contributed to ovarian diseases including polycystic ovarian syndrome (PCOS), primary ovarian insufficiency (POI), ovarian aging and other ovarian function disorders. However, the complex and subtle mechanism of m6A modification involved in female reproduction and fertility is still unknown. In this review, we have summarized the current findings of the RNA m6A modification and its regulators in ovarian life cycle and female ovarian diseases. And we also discussed the role and potential clinical application of the RNA m6A modification in promoting oocyte maturation and delaying the reproduction aging.

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“…Inactivation of METTL3 in mice oocytes also leads to DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation [ 37 ]. Among readers of m 6 A methylation, studies confirmed that the protein level of FTO, but not ALKBH5, was significantly decreased in human aged ovaries and in ovaries of women diagnosed with premature ovarian insufficiency [ 38 , 39 ]. Knocking down FTO, rather than ALKBH5, resulted in a decreased proliferation rate, increased apoptosis rate, and decreased cell viability in human ovarian granulosa cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve

Liu

Yang

et al. 2022

BMC Genomics

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Background The emerging epitranscriptome plays an essential role in female fertility. As the most prevalent internal mRNA modification, N6-methyladenine (m6A) methylation regulate mRNA fate and translational efficiency. However, whether m6A methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed m6A transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group). Results m6A methylation distribution was highly conserved and enriched in the CDS and 3’UTR region. Besides, an increased number of m6A methylated genes were identified in the older group. Bioinformatics analysis indicated that m6A methylated genes were enriched in the FoxO signaling pathway, adherens junction, and regulation of actin cytoskeleton. A total of 435 genes were differently expressed in the older group, moreover, 58 of them were modified by m6A. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by m6A, were validated using qRT-PCR and might be involved in the decreased ovarian functions in the aging ovary. Conclusions Hence, our finding revealed the transcriptional significance of m6A modifications and provide potential therapeutic targets to promote fertility reservation for aging women.

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Decreased expression of m6A demethylase FTO in ovarian aging

Cited by 24 publications

References 26 publications

RNA m6A methylation regulators in ovarian cancer

RNA m6A methylation regulators in ovarian cancer

The Role of m6A on Female Reproduction and Fertility: From Gonad Development to Ovarian Aging

Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve

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