METTL14-mediated epitranscriptome modification of MN1 mRNA promote tumorigenicity and all-trans-retinoic acid resistance in osteosarcoma

Li, Hongbo; Huang, Gang; Tu, Jian; Lv, Dongming; Jin, Qinglin; Chen, Jun-Kai; Zou, Yutong; Lee, Dung‐Fang; Shen, Jingnan; Xie, Xianbiao

doi:10.1016/j.ebiom.2022.104142

Cited by 28 publications

(20 citation statements)

References 59 publications

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“…In T-cell acute lymphoblastic leukemia, IGF2BP2 impels cell chemoresistance and survival via directly binding and stabilizing m 6 A-modified NOTCH1 mRNA [ 70 ]. In addition, METTL14-mediated MN1 methylation raises the stability and translation of MN1 transcript through the IGF2BP2-dependent pathway, prompting all-trans-retinoic acid resistance and progression in osteosarcoma [ 71 ].…”

Section: Introductionmentioning

confidence: 99%

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

Zhu

Ling

2023

Biomark Res

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N6-methyladenosine (m6A) is the most prevalent and well-characterized internal chemical modification in eukaryotic RNA, influencing gene expression and phenotypic changes by controlling RNA fate. Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) preferentially function as m6A effector proteins, promoting stability and translation of m6A-modified RNAs. IGF2BPs, particularly IGF2BP1 and IGF2BP3, are widely recognized as oncofetal proteins predominantly expressed in cancer rather than normal tissues, playing a critical role in tumor initiation and progression. Consequently, IGF2BPs hold potential for clinical applications and serve as a good choice for targeted treatment strategies. In this review, we discuss the functions and mechanisms of IGF2BPs as m6A readers and explore the therapeutic potential of targeting IGF2BPs in human cancer.

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Section: Introductionmentioning

confidence: 99%

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

Zhu

Ling

2023

Biomark Res

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“…Quantification was performed in comparison with the standard curve obtained from pure nucleoside standards run with the same batch of samples. The m 6 A level was calculated as the ratio of m 6 A to A based on the calibrated concentrations [ 36 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner

Cheng

Xue

et al. 2023

Genes

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Cardiac fibrosis and cardiomyocyte apoptosis are reparative processes after myocardial infarction (MI), which results in cardiac remodeling and heart failure at last. Tenascin-C (TNC) consists of four distinct domains, which is a large multimodular glycoprotein of the extracellular matrix. It is also a key regulator of proliferation and apoptosis in cardiomyocytes. As a significant m6A regulator, METTL3 binds m6A sites in mRNA to control its degradation, maturation, stabilization, and translation. Whether METTL3 regulates the occurrence and development of myocardial infarction through the m6A modification of TNC mRNA deserves our study. Here, we have demonstrated that overexpression of METTL3 aggravated cardiac dysfunction and cardiac fibrosis after 4 weeks after MI. Moreover, we also demonstrated that TNC resulted in cardiac fibrosis and cardiomyocyte apoptosis after MI. Mechanistically, METTL3 led to enhanced m6A levels of TNC mRNA and promoted TNC mRNA stability. Then, we mutated one m6A site “A” to “T”, and the binding ability of METTL3 was reduced. In conclusion, METTL3 is involved in cardiac fibrosis and cardiomyocyte apoptosis by increasing m6A levels of TNC mRNA and may be a promising target for the therapy of cardiac fibrosis after MI.

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“…Subsequently, dm6A may be enriched and subjected to sequencing. segments for sequencing (20), which is widely used in investigating methylated RNAs (114,115).…”

Section: M6a-seal-seqmentioning

confidence: 99%

Novel insight into the functions of N⁶‑methyladenosine modified lncRNAs in cancers (Review)

Chen

et al. 2022

Int J Oncol

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Emerging evidence has suggested that N 6 -methyladenosine (m6A) modification, a typical RNA methylation modification, controls the fate of modified transcripts and is involved in the pathogenesis of various human diseases, such as metabolic disorders, nephropathology, osteoarthritis and malignant tumours. Long noncoding RNAs (lncRNAs), transcripts of >200 nt in length, have also been indicated to be involved in various diseases by participating in processes such as epigenetic modifications, transcriptional alternations and posttranslational regulation. Recent studies revealed that lncRNAs were widely modified by m6A, which has a critical role in various cellular processes that are associated with numerous disorders, particularly human cancers. The present review first examined functions of m6A modification of lncRNAs, including changing the lncRNA structure, mediating transcriptional regulation, affecting mRNA precursor splicing, and regulating lncRNA stability and translation. Furthermore, the regulatory mechanisms of m6A-modified lncRNAs in cancers were summarized and the up-to-date detection methods and prediction tools for identifying m6A sites on lncRNAs were presented. In addition, viewpoints on potential future directions in the field were discussed, including more accurate detection methods, roles of lncRNAs-encoded micropeptides in cancers, the relationship

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METTL14-mediated epitranscriptome modification of MN1 mRNA promote tumorigenicity and all-trans-retinoic acid resistance in osteosarcoma

Cited by 28 publications

References 59 publications

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner

Novel insight into the functions of N⁶‑methyladenosine modified lncRNAs in cancers (Review)

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METTL14-mediated epitranscriptome modification of MN1 mRNA promote tumorigenicity and all-trans-retinoic acid resistance in osteosarcoma

Cited by 28 publications

References 59 publications

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner

Novel insight into the functions of N6‑methyladenosine modified lncRNAs in cancers (Review)

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Novel insight into the functions of N⁶‑methyladenosine modified lncRNAs in cancers (Review)