UPF1 (UPF1 RNA Helicase And ATPase)

TC m 6 A sites mark 1,386 genes essential for core cellular processes like autophagy and homeostasis, showing stable expression and evolutionary constraint. Pan-cancer analysis reveals that TC m 6 A genes are disproportionately differentially expressed, alongside with altered RBM15/B expression, suggesting that disruption of this stable m 6 A layer may contribute to transcriptional changes in cancer.

We define the coordinated roles of the splicing factor SRSF3 and the RNA surveillance factor UPF1 in regulating p53 mRNA isoform expression, thereby linking splicing fidelity with RNA surveillance during transcription. Our findings highlight the SRSF3-UPF1 axis for preventing oncogenic p53β protein isoform accumulation, offering a potential therapeutic target to restore p53 function and impede cancer progression.

CAPZA1 acts as a tumor suppressor in ESCC, with its function dependent on genotype. The CAPZA1[T] variant binds hnRNP K and PTBP1 to stabilize its mRNA and inhibit tumor aggressiveness, whereas the CAPZA1[G] allele promotes UPF1-mediated mRNA decay and diminishes this protective effect. These findings reveal a novel post-transcriptional regulatory mechanism underlying ESCC progression and highlight CAPZA1 genotype as a potential prognostic marker and therapeutic target.

Silencing lnc-APUE blocked TGFβ1-driven migration and invasion, identifying lnc-APUE as a downstream target and critical mediator of TGFβ1 signaling. Collectively, we define a new TGFβ1/SMAD/lnc-APUE/E-cadherin axis: TGFβ1 activates lnc-APUE to promote cancer metastasis through Alu element-driven STAU1-mediated CDH1 mRNA decay and subsequent E-cadherin downregulation.

We demonstrate that the endonuclease SND1 is SUMOylated at K513 in response to stresses such as oxidative stress and Cisplatin...Together, our findings reveal a novel oncogenic axis in which stress-induced SUMOylation of SND1 links tumor microenvironment stress to miRNA degradation. This SUMO1-SND1/miR-chr5_25226/MAPK10 pathway identifies the targeting of SND1 SUMOylation as a potential therapeutic strategy to modulate oncogenic miRNA decay and enhance chemosensitivity.

Our findings demonstrate that RPL7A promotes LUAD progression through circRANBP17-UPF1-mediated SIRT6 degradation, positioning RPL7A as a potential therapeutic target in LUAD.

Moreover, coculture with UPF1-knockdown NPC cells promoted macrophage M2 polarization and migration and suppressed CD8+ T-cell activation. Our findings suggest that reduced expression of UPF1 in NPC might contribute to tumor progression.

Surface residue mapping of SMG1 kinase revealed that it engages with SMG8, SMG9, and UPF1 in a sequential binding order, displaying the highest affinity for SMG8. Overall, these findings contribute to the mechanistic understanding of molecular properties for different RBPs from the NMD process, which can be the basis of developing new therapeutic strategies against genetic disease or cancer.

These changes reduced efficacy of Ras pathway-targeting drugs such as trametinib due to NF-κB-dependent enhancement of the glucuronidation detoxifying pathway, likely through modulating gene transcription and glucose uptake...The efficacy of WNT/MEK drug inhibitor combinations was further enhanced by targeting brm, shg, ago, rhoGAPp190, and upf1, potential biomarkers for patients responsive to this dual therapeutic approach. These findings shed light on how genetic complexity impacts drug resistance and a strategy to overcome it.

Ailanthone exhibits significant, effective, broad-spectrum anti-tumor effects with multiple targets and mechanisms in both in vitro and in vivo models. However, challenges remain for its clinical application of ailanthone due to its short half-life, low bioavailability and off-target effects. Chemical proteomic strategies, structure-activity relationship (SAR) optimization, delivery systems and combination strategies are urgently needed to overcome these challenges.

UPF1 cKO mice showed increased tumor burden compared to WT mice, which was rescued by UPF1 restoration. In conclusion, UPF1 attenuates CD8+ T cell exhaustion and suppresses glioma progression by destabilizing CD52 mRNA.

Manipulating Wnt signalling can further regulate 3UI-splicing of Wnt components. Our results indicate that 3' UTR splicing is not a rare occurrence and 3UI-splicing can regulate transcript expression in multiple ways, some of which are likely to be EJC-independent.