NSUN2 (NOP2/Sun RNA Methyltransferase 2)

The observed reductions in tumor burden and key biomarkers corroborate the therapeutic potential of this approach. Collectively, these preclinical findings suggest that electroacupuncture and moxibustion, as non-pharmacological adjunctive therapies, hold translational potential for modulating tumor metabolism and slowing HCC progression, warranting further clinical investigation.

NSUN2-mediated m5C modification of EPYC contributed to GC cell growth and metastasis, which provided a novel regulatory axis for understanding the pathogenesis of GC.

Functionally, depleted NSUN2 inhibits the proliferation and migration of TNBC cells significantly. Our study reveals the critical role of NSUN2 in regulating the immune microenvironment of TNBC, provides a theoretical foundation for its potential as a novel immunotherapy target, addresses the knowledge gap regarding NSUN2's immunoregulatory mechanisms in TNBC, and demonstrates significant clinical translational potential.

Our findings indicate that NSUN2 partially negatively regulates TP53 mRNA stability, promoting malignant progression and acting as an oncogene in NPC by downregulating TP53 through m5C modification. Thus, targeting the NSUN2/TP53 axis could be a potential therapeutic strategy for NPC.

Conversely, NSUN2 overexpression conferred ferroptosis resistance, reducing iron accumulation and restoring GPX4 expression even under erastin treatment...Notably, treatment with an autophagy inhibitor (3-MA) or a ferroptosis inhibitor (Fer-1) partially restored tumor growth in NSUN2-knockdown cells, validating the critical role of autophagy and ferroptosis in NSUN2-mediated OSCC progression. These findings identify the NSUN2-YBX1-SQSTM1/P62 axis as a key regulator of autophagy-dependent ferroptosis in OSCC, highlighting NSUN2 as a promising epitranscriptomic target to enhance ferroptosis induction for OSCC therapy.

IL-6 also recruited DLAT to acetylate NSUN2 at K229 site and increased association affinity between NSUN2 and KIF26B. Together, these established a KIF26B/NSUN2/m5C/IL-6 positive feedback loop, suggesting that targeting KIF26B may be a promising therapeutic strategy for BCa.

Moreover, NCAPG promoted GPX4 expression in a NSUN2-dependent manner, which also promoted resistance to ferroptosis in HCC. Collectively, the current study identified NCAPG protected HCC cells from undergoing ferroptosis, emphasizing NCAPG as an optional target for potentially developing anti-cancer therapy and improving the effects of ferroptosis in HCC treatment.

Our results demonstrate that NSUN2 facilitates leukemogenesis by increasing FTH1 expression and enhancing global protein synthesis in an m5C-dependent manner. Targeting NSUN2 might provide a promising therapeutic strategy for B-ALL.

Further in vivo analyses suggested that NSUN2 silencing suppressed ESCC growth and metastasis in vivo by regulating SLC7A5 expression. In conclusion, increased NSUN2 derived by P300/SP1 complex-mediated histone acetylation promoted the growth, metastasis and glutamine metabolism of NSCLC by stabilizing SLC7A5 mRNA via m5C modification.

The influence of NSUN2 or the m5C reader YBX1 in CCT5 mRNA was analyzed by RNA immunoprecipitation assay and Actinomycin D treatment...Our study indicates that NSUN2 enhances the stability of CCT5 mRNA through a YBX1-m5C-dependent manner to drive LUAD progression. Targeting the NSUN2/CCT5 axis may be a potential approach to combat LUAD.

In summary, nanoPue improves Dox therapeutic efficacy by decreasing angiogenic factors via regulating NSUN2 in HCC. This study may provide a potential avenue for advancing nanoPue to enhance chemotherapeutic agents in HCC therapy and supply a theoretical support for the clinical application of nanoPue.

This study identifies NSUN2 as a critical regulator of TNBC progression through tRNAVal-CAC m5C modification and codon-biased translation of glycolysis-related mRNAs. Our findings reveal a novel NSUN2-tRNAVal-CAC axis that orchestrates metabolic reprogramming and translational control in TNBC, offering a promising prognostic biomarker and therapeutic target.