METTL1 (Methyltransferase 1, TRNA Methylguanosine)

The random forest model, based on scRNA-seq, shows high predictive value for survival and immunotherapy sensitivity in gastric cancer patients. This study underscores the potential of METTL1 as a biomarker in enhancing the efficacy of gastric cancer immunotherapy.

In summary, our novel approaches address the pressing need for reliable and accessible methods to detect RNA m7G methylation in human cells. These advancements hold the potential to catalyse future investigations in the critical field of epitranscriptomics, shedding light on the complex regulatory roles of m7G in gene expression and its implications in cancer biology.

WDR4 may contribute to HCC pathogenesis by interacting with and regulating the expression of METTL1 to synergistically modulate the m7G modification of target mRNAs in tumor cells.

Our study elucidates the functional role of METTL1 in AM's invasive development and prognosis. High METTL1 expression is linked to postoperative recurrence, and METTL1 appears to promote AM invasiveness through the MAPK signaling pathway. These findings contribute to a better understanding of AM pathogenesis and may guide future therapeutic strategies.

Additionally, inhibition of OXPHOS biochemically negated METTL1's impact on anlotinib resistance. Overall, this study underscores the pivotal role of METTL1-mediated m7G tRNA modification in anlotinib resistance and lays the groundwork for novel therapeutic interventions to counteract resistance in OSCC.

Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.

Our study indicated that four polymorphisms in m7G-mediated genes contribute to neuroblastoma susceptibility in the eastern Chinese population. However, our findings should be verified further by large-scale and well-designed studies.

In addition, this study constructed a protein interaction network network including METTLs and mRNA risk signature genes related to tumor microenvironment remodeling based on single-cell sequencing. In conclusion, this study provides a theoretical basis for the mechanism, biomarker screening, and treatment of HCC.

Our study revealed that the abundance of the mG modification in tRNA was drastically reduced in CRC cells dependent on the HIF-1α-mediated inhibition of METTL1 transcription under hypoxic conditions.

Doxorubicin and platinum are widely used in the frontline treatment of osteosarcoma, but resistance to chemotherapy limits its curative effect...Moreover, the reduction of FTH1 translation dramatically increases cell ferroptosis and promotes the sensitivity of osteosarcoma cells to chemotherapy drugs. Collectively, our study demonstrates the METTL1/pri-miR-26a/FTH1 axis signaling in osteosarcoma and highlights the functional importance of METTL1 and mG methylation in the progression and chemotherapy resistance of osteosarcoma, suggesting that reprogramming RNA mG methylation as a potential and promising strategy for osteosarcoma treatment.

To study the gene expression patterns in HB, we performed RNA-seq analysis and qPCR validation to reveal differential expression of four candidate genes (IGF1R, METTL1, AXIN2, and TP53) in tumors compared to nonneoplastic liver tissue in HB patients (P-Val<0.01). These findings shed lights on the molecular mechanisms underlying HB development and facilitate to advance future personalized diagnosis and therapeutic interventions of HB.

Significant differences in tumor biological functions and immunophenotypes occurred among the different subgroups. The m7G-TME classifier offers a promising tool for predicting prognosis and immunotherapeutic responses in BC, which could support personalized therapeutic strategies.

In addition, we proposed several FDA-approved cancer-targeted drugs for various cancer types through PRISM drug screens, such as cabazitaxel for VHL-mutated kidney cancer and alectinib for lung cancer with NRAS or KRAS mutations. Leveraging pathway information can enhance the concordance of shRNA and CRISPR screens and provide clinically relevant findings such as the potential efficacy of dasatinib, an inhibitor of SRC, for colorectal cancer patients with mutations in the WNT signaling pathway. These analyses revealed that taking signaling pathway information into account results in the identification of more promising SL interactions.

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Importantly, the inhibitory effects of METTL1 knockdown on the proliferation of HNSC, esophageal cancer (ESCA), stomach adenocarcinoma (STAD), and colon adenocarcinoma (COAD) were significantly mitigated by over-expression of CDK4. Taken together, this study expands the understanding of epigenetic mechanisms involved in tumorigenesis and identifies the METTL1/CDK4 axis as a potential therapeutic target for digestive system tumors.

Mechanistically, we unveiled that P300 can form a complex with SP1 and bind to the promoter region of the METTL1 gene via SP1, thereby mediating METTL1 transcriptional upregulation in CRPC. Subsequently, our findings indicated that METTL1 leads to enhanced mRNA stability of CDK14 by adding m7G modifications inside its mRNA, ultimately promoting CRPC progression.

The potency was successfully improved by 8000-fold as measured by a homogeneous time-resolved fluorescence assay. The optimized compound is selective against the off-targets RNA methyltransferases METTL1 and METTL16.

This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.

In addition, we combined single-cell sequencing datasets and immune escape-related checkpoints to construct an immune escape-related protein-protein interaction(PPI) network. In conclusion, M7G methylated core genes (METTL1 and WDR4) and associated RNA risk signatures are associated with prognosis and immune escape in HCC.

Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed mG tRNA methylation in cancer cell translation control and tumour biology.

No abstract available

Furthermore, TROP2 expression was significantly positively correlated with the expression levels of METTL3 and METTL1 in BCa patients. Overall, our results revealed that METTL3/METTL1-mediated dual mA/mG RNA modifications enhanced TROP2 translation and promoted BCa development, indicating a novel RNA epigenetic mechanism in BCa.

eIF4E antisense oligonucleotide drug (4EASO) and Ribavirin are the most mature trials that competitively inhibit the binding of eIF4E to m7G-cap...In the future, we look forward to an ongoing investigation into the role of m7G modification in tumors and drug resistance to m7G-related therapies to be solved. Therefore, the clinical application would be put into practice as soon as possible.

tRNA methylation and mRNA translation profiling indicate that METTL1/WDR4 modified tRNAs enhance translation of mRNAs with more mG tRNA-decoded codons, including extracellular matrix (ECM) remodeling effectors, which facilitates osteosarcoma progression and chemoresistance to doxorubicin. Our study demonstrates METTL1/WDR4 mediated tRNA mG modification plays crucial oncogenic functions to enhance osteosarcoma progression and chemoresistance to doxorubicin via alteration of oncogenic mRNA translation, suggesting METTL1 inhibition combined with chemotherapy is a promising strategy for treatment of osteosarcoma patients.