CNOT3 (CCR4-NOT Transcription Complex Subunit 3)

In an orthotopic lung cancer mouse model treated with erastin (a ferroptosis inducer) and programmed cell death protein 1 (PD-1) blockade, the role of TIMELESS in therapeutic response was assessed via flow cytometry and multiplex immunofluorescence (mIF)... TIMELESS recruits CNOT3 to accelerate TF mRNA degradation, thereby suppressing ferroptosis and promoting LUAD growth. These findings suggest that the TIMELESS/TF regulatory axis may be a promising therapeutic target for LUAD.

No significant associations were found between the genetic variants and hypersensitivity or pancreatitis (p > 0.05). No statistically significant associations were observed between the selected variants and PEG-ASNase-related hypersensitivity or pancreatitis in this cohort.This study highlights the importance of ancestry-informed approaches in pharmacogenomic research for ALL.

Critically, in vitro and in vivo experiments established CNOT3 as a novel oncogene, with its knockdown significantly inhibiting tumor growth (p<0.001). This study is the first to demonstrate that mixed heavy metal exposure synergistically increases PCa risk and identifies CNOT3 as a biologically significant biomarker and therapeutic target in heavy metal-related PCa development.

The senescent cell hallmarks were more prominent in the culture after additional treatment with BI 2536, a polo-like kinase 1 inhibitor. These results suggest that CNOT3 downregulation followed by BI 2536 treatment upregulates the hallmarks of cellular senescence in A549 cell culture.

In the validation cohort, UBE2Z, CNOT3, and EID3 were correlated with liver function indicators in patients with hepatitis B-related HCC. Overall, UBE2Z, CNOT3, and EID3 emerged as cancer-specific biomarkers for HBV-related liver disease, providing a scientific basis for clinical application.

Furthermore, CNOT3 associates with the protein network largely consisting of ribosomal proteins and translation elongation factors in leukemia cells. Overall, our work elicits the direct requirement for translation efficiency in tumorigenesis and propose targeting the post-transcriptional circuitry via CNOT3 as a therapeutic vulnerability in AML.

One of the main limitations of the frontline pegaspargase (PEG) chemotherapy is the development of hypersensitivity reactions and subsequent development of anti-asparaginase neutralizing antibodies that lead to PEG inactivation...Instead of a single SNP association approach, identifying combinations of variations in pathway specific genes provides a more robust means to predict drug response. Our preliminary results provide a rationale for identification of genome level variations in this cohort and association analysis to establish clinically relevant pharmacogenomics score to optimize PEG treatment.

Depleting CNOT3 in vitro and in vivo sensitized the drug-resistant cells to gefitinib treatment and inhibited metastatic progression. These results give novel insights into the role of CNOT3 in lung cancer malignancy and provide a theoretical basis for the development of therapeutic strategies to solve acquired resistance to EGFR-TKIs.

Association analysis between PNPLA3 rs738409 and liver function could not be investigated due to a lack of clinical information. In conclusion, none of the tested genes did predict L-asparaginase hypersensitivity in an Ethiopian pediatric ALL patients.

In conclusion, our findings indicate that the combination of TP53 and/or KRAS variants with poor treatment response identifies a subgroup of patients with a dismal prognosis who might benefit from treatment intensification or experimental treatment approaches such as CD1a or CD7 CAR-T cell therapy. T-ALL, Acute lymphoblastic leukemia, High risk, Risk factor

Immunoprecipitation of CNOT3 and mass spectrometry analysis of co-precipitated proteins captured proteins involved in protein synthesis including translation elongation factors and ribosomal proteins, suggesting a functional interaction of CNOT3 with the translation machinery. Overall, we uncovered a critical role of the CCR4-NOT deadenylation complex in myeloid leukemia and nominated CNOT3 as a potential target for AML therapy.

Additionally, CNN1 may regulate NIR_5347_ING4, CNOT3 may regulate NIR_17935_DNAJC2, and DQX1 and LENG9 may regulate NIR_422_SLC5A1. Overall, our findings establish a theoretical foundation for the precise targeted treatment of CTCLs with HDACi.