POLA1 (DNA Polymerase Alpha 1)

These findings support the formation of disease-characteristic immune complexes in oral cancer and highlight the potential of immune complexome analysis in saliva for understanding oral cancer pathogenesis and therapeutic targets.

Five druggable targets were selected for validation, with four of the five agents tested proving effective against human MPNST cells (the POLA1 inhibitor clofarabine, DNTT inhibitor cordycepin, BCL6 inhibitor 79-6 and LPAR1/3 inhibitor Ki16425). Clofarabine was especially effective, potently reducing cell numbers at low nanomolar concentrations and inducing a senescent phenotype, possibly via the p53/p21 pathway. These results demonstrate the utility of cross-species functional oncogenomics for the discovery of novel therapeutic targets relevant to human MPNSTs and suggest that clofarabine warrants further evaluation for its therapeutic potential.

Our findings may have important clinical implications for utilizing NEIL3 as a potential prognostic biomarker to stratify EC patients and as a target to enhance immunotherapy response in endometrial cancer. However, our NEIL3 overexpression associated observation still requires further experimental-based scientific validation studies.

Drug sensitivity analysis identified potential therapeutic agents correlated with the expression of the five prognostic genes. Our findings underscore the importance of MM in CC progression and provide potential therapeutic targets for CC.

Distinct protein associations were found: ATR, POLA1, BLM, SP100, and PPP1R15A for early recurrence, and SERPINA1, TGFB2, SERPING1, and CAD for late recurrence, with strong interactions with chemotherapeutic drugs. This study successfully demonstrated the use of PMFs for rapid discrimination between early and late recurrence in CCA and identified potential serum peptide biomarkers to improve accuracy in recurrence classification.

Accordingly, BRCA1 deficiency sensitizes cells to POLA1 inhibition. Thus, our findings establish the POLA complex as important player in PARPi-induced fork acceleration and provide evidence that lagging strand synthesis represents a targetable vulnerability in BRCA1-deficient cells.

In conclusion, the synthetic lethality between ATR/CHK1 and POLA1 might represent a novel and promising approach for individualized cancer therapy: First, alterations of POLA1 could serve as a screening parameter for increased sensitivity towards ATR and CHK1 inhibitors. Second, alterations in the ATR-CHK1 pathway might predict in increased sensitivity towards POLA1 inhibitors.

Subsequent preclinical experiments demonstrated significant cytotoxicity of POLA1 silencing in combination with CHK1i in platinum-resistant HGSOC cell line models. Therefore, POLA1 expression may be predictive for CHK1i resistance, and the concurrent POLA1 inhibition may improve the efficacy of CHK1i monotherapy in this hard-to-treat population, deserving further investigation.

The binding affinity scores of glucose molecules for the 3 proteins were found to be closer to positive controls. Therefore, we report the glucose binding ability of 3 secretion-related proteins and a possible direct role of intracellular glucose molecules in GSIS.

In this study, we delved into the underlying mechanisms of specific BCR-ABL tyrosine kinase inhibitors (imatinib, nilotinib, ZM-306416, and AT-9283) in human melanoma A375P cells. Consequently, the expression of the E2F target genes (CCNA2, CCNE1, POLA1, and TK-1) was markedly suppressed in nilotinib and AT9283-treated A375P cells. In summary, our findings suggest that BCR-ABL tyrosine kinase inhibitors may regulate the G1-to-S transition in human melanoma A375P cells by modulating the RB-E2F complex.

The study suggests the novel role of POLA1 and its association with SMP30 in liver tumorigenesis. The different expression levels of POLA1 and SMP30 expression levels in male and female ultimately resulted in gender disparity in the liver tumorigenesis.

The proteomics profiles revealed 197 proteins significantly differentially altered upon ST1926 treatment of GBM cells involved in various cellular processes. We explored the differential gene and protein expression of significantly altered proteins in GBM compared to normal brain tissues.