METTL16 (Methyltransferase 16, RNA N6-Adenosine)

However, further in-depth studies are required to validate these findings. By comprehensively summarizing the current literature on METTL16, we provide a theoretical basis for its application as a diagnostic and prognostic marker as well as a potential therapeutic target for digestive system cancers.

Notably, targeting CDK13 with the small-molecule inhibitor 1NM-PP1 potentiates METTL16 depletion-mediated anticancer effects. Our findings establish a kinase-RNA modifier axis that links CDK13 to epitranscriptomic control of lipid metabolism, positioning the CDK13-METTL16-ACLY pathway as a promising target for precision therapies against ccRCC.

Proteomics analysis further elucidated the relationship and mechanisms among METTL16, astaxanthin, and ferroptosis, revealing significant changes in several key proteins associated with ferroptosis-related pathways, mitochondrial energy metabolism, oxidative stress, and fatty acid metabolism. This study demonstrates that astaxanthin inhibits CRC cell growth and delineates its relationship and mechanisms with METTL16 and ferroptosis, providing a new direction for CRC treatment.

Additionally, METTL16-mediated m6A modification of EEF1A1 mRNA activates the m6A-IGF2BP1 axis, resulting in increased EEF1A1 protein levels and enhanced resistance to ENZ-induced apoptosis. These findings uncover a novel UFL1-METTL16-EEF1A1 signaling pathway that drives ENZ resistance, suggesting that targeting this cascade may offer a promising therapeutic strategy for overcoming ENZ resistance in prostate cancer.

In vivo, METTL16 silencing repressed the cervical cancer tumor growth. Therefore, these findings revealed that novel m6A writer METTL16 promoted the cervical cancer tumorigenesis by targeting FTH1-dependent ferroptosis, which providing distinct insights for cervical cancer.

This review provides a detailed examination of METTL16's functions and regulatory mechanisms in cancer, emphasizing its m6A-dependent and m6A-independent roles in regulating RNA stability and function. Furthermore, it proposes that targeting METTL16 represents a promising avenue for cancer therapy.

LINC01940 is a cancer-testis lncRNA that promotes GC progression and cisplatin resistance by enhancing ribosome biogenesis via the METTL16/IGF2BP3-TAF15-NOL11 axis. These findings suggest its potential as a prognostic biomarker and therapeutic target in GC.

Recent evidence suggests that METTL16 also modulates the tumor microenvironment (TME), potentially affecting immune cell infiltration, immune checkpoint expression, and tumor immune evasion. Collectively, METTL16 emerges as a pivotal epitranscriptomic regulator linking RNA modification, tumor progression, and immune modulation, offering new avenues for precision oncology.

In particular, it is demonstrated that HPD regulates colorectal cancer ferroptosis by methylating SLC7A11/GPX4 through a moonlighting function. These findings uncover the moonlighting function of HPD in m6A-mediated ferroptosis and underscore the potential to target the m6A methyltransferase activity of HPD for cancer treatment.

Furthermore, correlation with clinical data from the TCGA database revealed that m6A-associated DEGs, such as HMGA1, ERO1A, LRFN4, SNTN, SLC2A1, DNASE2B, and VSIG2, were prognostically significant in NSCLC. This study underscores the pivotal role of m6A modifications in NSCLC and highlights the potential of dRNA-seq for identifying RNA epigenetic changes that may serve as novel therapeutic targets.

Two METTL16 somatic cancer-associated mutants (G110C and R241Dfs*2) displayed reduced methylation activity. This mutational analysis expands our understanding of how specific domains and residues contribute to substrate-binding activity and methylation of U6 snRNA catalyzed by METTL16.

This work provides evidence that multitargeted METTL may have stronger inhibition of HCC cell proliferation. Further in vivo validation, toxicity analysis as well as molecular insights will determine the therapeutic utility against HCC.