UPF1 (UPF1 RNA Helicase And ATPase)

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.

Mechanistically, asymmetric di-methylation of UPF1 R433 by protein arginine methyltransferase 4 inhibits the autophagic degradation of UPF1, and inhibiting UPF1 R433 methylation can weaken NMD, thus increasing the immunogenicity and anti-PD-1 sensitivity of CRC, regardless of MSS or MSI status. Our study highlights the potential of combination strategies in CRC immunotherapy, promising to expand the beneficiaries of immunotherapy and provide insights for new therapeutic targets.

Additionally, circRNA-RBP bioinformatic analysis identified common binding partners, including AGO2, CPSF7, TARDBP, UPF1, and LIN28B, suggesting roles in post-transcriptional regulation. Our data highlight circ_0001522, circ_0001278, and circ_0001801 as promising prognostic and therapeutic circRNA targets for breast cancer, offering new avenues for improving breast cancer prognosis and treatment.

UPF1 inhibited cervical cancer cell migration and invasion through the regulation of nonsense-mediated decay of BMP6 and lncRNA WAKMAR2.