Novel insights into roles of N6-methyladenosine reader YTHDF2 in cancer progression

Liu, Rui; Yin, Jianfei; Kong, Guangyao; He, Aili

doi:10.1007/s00432-022-04134-7

Cited by 5 publications

(2 citation statements)

References 108 publications

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“…Mechanistic analyses in the present study indicated that METTL3 may inhibit the expression of RRAS by increasing its m6A modification level. YTHDF2 was the first specific m6A recognition protein identified to regulate mRNA degradation ( 48 , 49 ). YTHDF2 also plays an integral role in tumorigenesis and malignant progression ( 50 , 51 ).…”

Section: Discussionmentioning

confidence: 99%

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS

Chen

Wang

et al. 2023

Oncol Rep

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The present study aimed to explore the potential roles of the methyltransferase-like 3 (METTL3)-mediated methylation of RAS related (RRAS) mRNA in the tumorigenesis and development of bladder cancer (BCa). For this purpose, the relative expression levels of METTL3 in BCa specimens and cell lines were measured using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. The association between the METTL3 expression level and the clinical characteristics of patients with BCa was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis databases. Cellular experiments were performed to confirm the effects of METTL3 on the proliferative, migratory and invasive capacities of BCa cells. RT-qPCR, western blot analysis, methylated RNA immunoprecipitation (MeRIP)-qPCR and dual-luciferase report assays were utilized to verify the METTL3/RRAS/YTH N 6 -methyladenosine (m6A) RNA binding protein 2 (YTHDF2) regulatory axis in BCa. The results revealed that METTL3 expression was markedly increased in BCa specimens and cell lines, and was associated with poor clinical characteristics of patients with BCa. In vitro and in vivo assays demonstrated that the silencing of METTL3 markedly suppressed the proliferative, migratory and invasive capacities of BCa cells. MeRIP-PCR and dual-luciferase report assays indicated that METTL3 could bind to the m6A sites of RRAS mRNA and suppress the transcriptional activity of RRAS. YTHDF2 could recognize the m6A sites of RRAS and mediate RRAS degradation. On the whole, the findings of the present study reveal the pivotal role of METTL3-catalyzed m6A modification in BCa tumorigenesis and development. The change could facilitate BCa tumor growth and metastasis by suppressing RRAS expression in an m6A YTHDF2-dependent manner. Targeting the METTL3/RRAS/YTHDF2 regulatory axis may thus prove to be a promising strategy for the diagnosis and therapy of BCa.

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Section: Discussionmentioning

confidence: 99%

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS

Chen

Wang

et al. 2023

Oncol Rep

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“…The mechanism by which m6A modification improves the translation efficiency is mainly dependent on the binding of reader proteins to protein factors that are required in the translation process, the presence of m6A in exons and surrounding stop codon regions may have an impact on protein production ( Liu R. et al, 2022 ). It has been indicated that ablation of METTL3 enhanced translation efficiency in mouse embryonic stem cells (mESCs) and embryoid bodies (EBs), demonstrating that m6A played a translational regulatory role ( Geula et al, 2015 ).…”

Section: Crosstalk Between N6-methyladenosine Modification and Rnas I...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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N6-methyladenosine reader YTHDF2 promotes multiple myeloma cell proliferation through EGR1/p21cip1/waf1/CDK2-Cyclin E1 axis-mediated cell cycle transition

et al. 2023

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Multiple myeloma (MM) is the second most common hematological malignancy. N6-methyladenosine (m6A) is the most abundant RNA modification. YTH domain-containing family protein 2 (YTHDF2) recognizes m6A-cotaining RNAs and accelerates degradation to regulate cancer progression. However, the role of YTHDF2 in MM remains unclear. We investigated the expression levels and prognostic role of YTHDF2 in MM, and studied the effect of YTHDF2 on MM proliferation and cell cycle. The results showed that YTHDF2 was highly expressed in MM and was an independent prognostic factor for MM survival. Silencing YTHDF2 suppressed cell proliferation and caused the G1/S phase cell cycle arrest. RNA immunoprecipitation (RIP) and m6A-RIP (MeRIP) revealed that YTHDF2 accelerated EGR1 mRNA degradation in an m6A-dependent manner. Moreover, overexpression of YTHDF2 promoted MM growth via the m6A-dependent degradation of EGR1 both in vitro and in vivo. Furthermore, EGR1 suppressed cell proliferation and retarded cell cycle by activating p21cip1/waf1 transcription and inhibiting CDK2-cyclinE1. EGR1 knockdown could reverse the inhibited proliferation and cell cycle arrest upon YTHDF2 knockdown. In conclusion, the high expression of YTHDF2 promoted MM cell proliferation via EGR1/p21cip1/waf1/CDK2-cyclin E1 axis-mediated cell cycle transition, highlighting the potential of YTHDF2 as an effective prognostic biomarker and a promising therapeutic target for MM.

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Novel insights into roles of N6-methyladenosine reader YTHDF2 in cancer progression

Cited by 5 publications

References 108 publications

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS

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

N6-methyladenosine reader YTHDF2 promotes multiple myeloma cell proliferation through EGR1/p21cip1/waf1/CDK2-Cyclin E1 axis-mediated cell cycle transition

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