m6A Modification in Non-Coding RNA: The Role in Cancer Drug Resistance

Chen, Chen; Guo, Yuying; Guo, Yaxin; Wu, Xinmin; Si, Chaohua; Xu, Yanxin; Kang, Qiaozhen; Sun, Zhenqiang

doi:10.3389/fonc.2021.746789

Cited by 16 publications

(6 citation statements)

References 156 publications

(214 reference statements)

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“…However, data from the TCGA database show that YTHDF3 is downregulated in CRC patients. , Nonetheless, our study mainly focused on OXAR CRC cell lines and tissues, which we suspect are different from patient-derived CRC tissues. Moreover, our results indicate that YTHDF3 binds to the 5′ UTR to control gene translation (Figure C), which is consistent with a previous study, showing that YTHDF3 induces gene translation of transcripts that are m6A-enriched at the 5′ UTR, , and YTHDF3 per se does not affect m6A methylation but may determine RNA fate and metabolism . Although it has been previously demonstrated that YTHDF3 is implicated in drug resistance and metastasis in lung cancer, , the molecular role of YTHDF3 in modulating gene translation in platinum resistance remains poorly understood.…”

Section: Discussionsupporting

confidence: 92%

“…Moreover, our results indicate that YTHDF3 binds to the 5′ UTR to control gene translation (Figure 3C), which is consistent with a previous study, showing that YTHDF3 induces gene translation of transcripts that are m6A-enriched at the 5′ UTR, 26,27 and YTHDF3 per se does not affect m6A methylation but may determine RNA fate and metabolism. 28 Although it has been previously demonstrated that YTHDF3 is implicated in drug resistance and metastasis in lung cancer, 13,14 the molecular role of YTHDF3 in modulating gene translation in platinum resistance remains poorly understood. The second important observation of our study is the synergistic effect of YTHDF3 with translation initiation factors in OXAR CRC cells, which is different from that in non-resistant cancer cells.…”

Section: ■ Discussionmentioning

confidence: 99%

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YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer

Zhao

Zhang

et al. 2022

ACS Chem. Biol.

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Oxaliplatin, as a first-line drug, frequently causes chemoresistance in colorectal cancer (CRC). The role of N6-methyladenosine (m6A) modification in multiple biological functions has been well studied. However, the molecular mechanisms underlying m6A methylation in modulating anti-cancer drug resistance in CRC remain obscure. In the present study, we found that YTH m6A RNA-binding protein 3 (YTHDF3) was highly expressed in oxaliplatin-resistant (OXAR) CRC tissues and cells. Moreover, we observed that YTHDF3 could recognize the 5′ untranslated region of significantly m6A-methylated RNAs, which were associated with tumor resistance and recruit eukaryotic translation initiation factor 3 subunit A (eIF3A) to facilitate the translation of these target genes. Furthermore, we determined that eukaryotic translation initiation factor 2 alpha kinase 2 (eIF2AK2) bridged YTHDF3 and eIF3A, enhancing the stability of the YTHDF3/eIF3A complex in OXAR CRC cells. Taken together, our data identified YTHDF3 as a novel hallmark and revealed the molecular mechanism of YTHDF3 on gene translation via coordination with eIF2AK2 in OXAR CRC cells.

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Section: Discussionsupporting

confidence: 92%

Section: ■ Discussionmentioning

confidence: 99%

YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer

Zhao

Zhang

et al. 2022

ACS Chem. Biol.

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“…A growing number of studies have shown that m6A methylation serve as a potential biomarker for therapy resistant cancer cells [ 90 – 92 ]. Methods of determining the m6A methylation includes LC-MS/MS, Colorimetric and MeRIP-seq.…”

Section: Methods Of Determining the M6a Methylationmentioning

confidence: 99%

The role of m6A methylation in therapy resistance in cancer

Zhuang

Tao

et al. 2023

Mol Cancer

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Cancer therapy resistance is the main cause of cancer treatment failure. The mechanism of therapy resistance is a hot topic in epigenetics. As one of the most common RNA modifications, N6-methyladenosine (m6A) is involved in various processes of RNA metabolism, such as stability, splicing, transcription, translation, and degradation. A large number of studies have shown that m6A RNA methylation regulates the proliferation and invasion of cancer cells, but the role of m6A in cancer therapy resistance is unclear. In this review, we summarized the research progress related to the role of m6A in regulating therapy resistance in cancers.

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“…N6-methyladenosine (m6A) methylation modifications are the most frequent internal RNA modifications in eukaryotes ( 12 ). A growing number of findings suggest that noncoding RNA level may be associated with m6A methylation modifications ( 13 ). For example, researchers have found that lncRNA XIST can form the RBM15/RBM15B-WTAP-METTL3 complex to regulate transcriptional silencing of genes, which recruits the silencing complex ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of m6A-related lncRNAs for thyroid cancer recurrence

Wang¹,

Su²,

Wei³

et al. 2023

Gland Surg

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Background: Although the prognosis of thyroid cancer (THCA) is generally good, many patients have a high risk of recurrence after treatment. N6-methyladenosine (m6A)-related long noncoding RNAs (lncRNAs) have been extensively studied in recent years. However, the potential of m6A-related lncRNAs to predict recurrence in THCA is unknown.Methods: RNA sequencing (RNA-seq) data and clinical information for THCA were downloaded fromThe Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DELs) were identified using the R package DESeq2. A coexpression network based on m6A-related genes and lncRNAs was constructed. The CIBERSORT algorithm and gene set enrichment analysis (GSEA) were used for immune-infiltrating cell estimation and clustering functional enrichment analysis, respectively. A Kaplan-Meier plot was used for prognostic analysis based on m6A-associated lncRNA risk patterns. The expression of lncRNAs in recurrent and nonrecurrent THCA tissues was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR).Results: A network of m6A-related lncRNAs containing 8 lncRNAs was constructed with good predictive power for recurrence in THCA. A total of 3 clusters were obtained, and cluster 1 was most associated with THCA recurrence. We found significantly lower levels of CD8 T cells and follicular helper T cells, and significantly higher levels of dendritic cells (DCs), M2 macrophages, resting DCs, regulatory T cells, and mast cells in cluster 1 patients. Pathway analysis revealed significant enrichment in natural killer cellmediated cytotoxicity, butyrate metabolism, and cell adhesion molecules in cluster 1. The m6A-related lncRNA risk model was effective in predicting progression-free survival (PFS) in patients with THCA recurrence. RT-qPCR analysis based on 40 THCA clinical samples from our center found the risk model to be a good predictor of recurrence in THCA patients.Conclusions: In summary, m6A-related lncRNAs may provide a novel predictive method for prognostic relapse in THCA patients.

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m6A Modification in Non-Coding RNA: The Role in Cancer Drug Resistance

Cited by 16 publications

References 156 publications

YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer

YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer

The role of m6A methylation in therapy resistance in cancer

Identification of m6A-related lncRNAs for thyroid cancer recurrence

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