HES4 (Hes Family BHLH Transcription Factor 4)

Using eight patient-derived cancer organoid models, we found that auranofin increased cisplatin efficacy in killing cancer organoids generated from clinically platinum-sensitive patients but also restored platinum response in a subset of organoid models developed from platinum-resistant patients. These studies underscore the potential of auranofin to improve platinum-based cancer therapy, particularly in Notch3-expressing cancers.

Overall, this study revealed that hypoxia-mediated HES4 promotes the proliferation and motility of HCC cell by enhancing the transcription of COL4A2. HES4 was a key therapeutic target and biomarker in HCC.

Additionally, through an integrated experimental approach including genetically modified cell lines, RNA/Chip-sequencing and single cell RNA-sequencing (scRNA-Seq) profiles of primary T-ALL samples, we revealed cell subsets with Notch-dimerization-dependent gene signature, which indirectly correlated with pro-apoptotic genes as well as directly associated with cell markers of poor clinical outcome in primary T-ALL samples. Taken together, these findings highlight the crucial role of NOTCH1 dimeric signaling in human T-cell leukemogenesis and T-ALL maintenance suggesting that a possible benefit can be obtained from a therapeutic strategy targeting NOTCH1-dimer signaling or its downstream effectors.

HES4 overexpression is associated with poor clinical outcomes and tumor progression. HES4 may serve as a novel prognostic marker and therapeutic target in HCC.

Conversely, knockout of BEST4 using CRISPR/Cas9 in CRC cells revitalises tumour growth and induces EMT. Furthermore, the low level of the BEST4 mRNA is correlated with advanced and the worse prognosis, suggesting its potential role involving CRC progression.

In addition, silencing B4GALNT1 was proved to enhance the tumor-killing efficiency of the programmed cell death protein 1 (PD-1)-targeting strategy in mouse model. In conclusion, this study evaluated B4GALNT1 as a prognostic predictor for HCC patients and revealed the mechanism of B4GALNT1 in microenvironmental remodeling, which extends the understanding of HCC progression and provides a novel auxiliary strategy for HCC immunotherapy.

This study provides profound insights into the molecular regulatory network of L-Arg in promoting the development of chicken embryos. The identified DEGs that promote cell proliferation and lipid metabolism can serve as novel targets for further developing methods to enhance early development of chicken embryos.

Finally, we demonstrate that lncRNA H19 is highly expressed in ATL patient samples and ATL cells and contributes to Notch signaling activation. Collectively, our results shed further light on the Notch pathway in ATL leukemia and reveal new therapeutic approaches to inhibit Notch activation in ATL cells.

Furthermore, HES4 protein stability is enhanced under EGFR activation, and increased HES4 levels facilitate EGFR-driven tumor growth and predict poor prognosis of lung adenocarcinoma. These findings illustrate an unidentified mechanism, underlying pyrimidine biosynthesis in the intersection between serine and choline catabolism, and underscore the physiological importance of HES4 in tumor metabolism.

Furthermore, post-administration of HeS not only inhibited demyelination and gliosis but also alleviated anxiety and depression in both acute and chronic CPZ-fed mice. This study presents compelling evidence supporting the potential of HeS as a promising small active compound for protecting OLs and preserving myelin in demyelinating diseases associated with emotional disorders.

Finally, HES4 was up-regulated in cancer samples in both TCGA-BLCA and GSE121711 datasets. This study identified HES4 as an independent prognostic factor for BLCA outcome based on MR and transcriptome analysis, which provides useful information for future research on and treatment of BLCA.