METTL3 (Methyltransferase Like 3)

Our work uncovers a previously unrecognized PRKN-METTL3-CLDN2 signaling network that orchestrates colorectal tumorigenesis, providing a compelling rationale for developing METTL3-targeted therapies against CRC.

In contrast, other JAK-STAT3 inhibitors such as ruxolitinib and knockdown of STAT3 does not replicate this effect, indicating that the anti-tumor effect of filgotinib is independent of JAK-STAT3 signaling. This study offers innovative insights and potential therapeutic strategies for the treatment of PDAC through EIF3A m6A.

To develop novel anti-leukemia therapies, a CNN model identified C191-0266 targeting METTL3, which exhibited potent anti-leukemia activity. It inhibited the proliferation of OCI-AML3, MOLM-13, and THP-1 cell lines with IC50 values of 16.91 μM, 19.01 μM, and 24.99 μM respectively, showed strong METTL3 binding (KD = 7.28 μM) and enzymatic inhibition (IC50 = 7.639 μM), enhanced Ara-C's cytotoxicity by suppressing Ara-C-induced protective autophagy, maintained stable binding to METTL3, regulated the NF-κB pathway to inhibit TNF-α overexpression in Ara-C-resistant cell lines, and had favorable pharmacokinetics and safety profiles via ADME assessments, thus holding promise as an anti-leukemia drug candidate.

METTL3 promotes PRAD progression by stabilizing VSTM2L expression through m6A methylation, thereby inhibiting ferroptosis. This study establishes a direct link between RNA methylation and ferroptosis in PRAD, revealing the METTL3/VSTM2L axis as a novel regulatory pathway and a potential therapeutic target.

circWDR85 acts as a novel m6A-modified circRNA that promotes BC bone metastasis by stabilizing c-Jun through CKB-mediated phosphorylation.

The cumulative risk score based on m6A pathway variants showed a strong association with PFS. These findings provide preliminary, hypothesis-generating evidence that genetic variations may contribute to inter-patient variability in outcomes and warrant further investigation as potential biomarkers in IM-treated GIST.

Experimentally, overexpression of SNORA12 in osteosarcoma cells and primary NK cells significantly upregulated TIGIT at both the mRNA and protein levels, while SNORA12 knockdown in NK92 cells reduced TIGIT expression. This pan-cancer analysis positions SNORA12 as a tumor type-specific prognostic biomarker and reveals its novel role as a positive regulator of TIGIT in osteosarcoma, offering a potential mechanistic link between snoRNA dysregulation and immune evasion.

Notably, reduced RNA m 6 A levels correlated with diminished HIV-1 latency reversal in both J-Lat cells and a primary central memory CD4 + T cell model. Together, these findings demonstrate differential potency and cytotoxicity among METTL3 inhibitors and support a critical role for m 6 A RNA modification in regulating HIV-1 latency reversal.

Following treatment with temozolomide (TMZ), the level of m6A modification was increased, facilitating YTHDF3-mediated DNA damage repair...Mechanistically, YTHDF3 recognizes the m6A binding site of DNA damage response genes (BRCA1, RAD51, RIF1 and 53BP1) and promotes their translation through m6A methylation, thereby initiating homologous recombination (HR) and nonhomologous end joining (NHEJ) repair to resist endogenous and exogenous DNA damage. Consequently, our study elucidates the crucial role of YTHDF3 in GBM and provides valuable insights into its significance in the DNA damage response and chemoresistance.

In this review, a comprehensive overview of the various actions of melittin and other components of bee venom on different types of cancer is provided. The research discusses their mechanisms of action and potential strategies to enhance efficacy and minimize toxicity.

In addition, STM2457 could inhibit tumor growth in subcutaneous xenotransplantation mouse model. Our findings suggested that STM2457 had great potential for the treatment of GC and could serve as a foundation for future clinical applications.