MED23 (Mediator Complex Subunit 23)

Consistently, overexpression of IGF2 in MED23-deficient HCC cells stabilizes NQO1 and partially restores cell growth and reduces apoptosis. Collectively, our findings underscore the significance of the MED23-IGF2-NQO1 axis in HCC progression and propose a novel therapeutic strategy for the treatment of HCC.

The PSO-based hybrid model effectively improved SVR performance in survival prediction for OC patients and identified key prognostic biomarkers. Despite its promising results and validation on independent datasets, limitations in generalizability and signs of overfitting suggest the model is not yet ready for clinical use. Further studies with larger, diverse datasets are recommended.

Consequently, MED23 deficiency led to hundreds of readthrough events and fusion transcripts, and the 3' RNA binding of MED23 is critical for the transcription termination regulation. Moreover, integrative analysis revealed that MED23 deficiency contributed to readthrough events in breast cancers, thus providing critical molecular insights into carcinogenesis.

In aged animals, it is found the abundance of CD103+ CD8+ T cells in the lung declines with age, accompanied by an accumulation of oxidative-damage-bearing AT2 cells. Collectively, the study establishes the vital function of CD103+ T cells in surveilling epithelial cells under oxidative stress to prevent malignancies, and unravels a potential immuno-dysregulation in the aged lung which contributes to tumorigenesis.

Our findings reveal that this HER2-ELF3-KRAS axis is exclusively activated in KRASG13D, driving aggressive oncogenic features and conferring resistance to cetuximab (CTX) therapy...Our study underscores the importance of HER2 as a key determinant in the unique biological characteristics of KRASG13D CRCs and highlights the therapeutic potential of targeting the HER2-ELF3-KRAS axis. By presenting YK1 as a novel pharmacological approach, we provide a promising strategy for developing tailored interventions for KRASG13D CRCs, contributing to the ongoing efforts in precision medicine for CRCs.

This suggests its potential as a viable therapeutic option for trastuzumab-resistant gastric cancers. In summary, compound 10 could be a novel alternative therapeutic strategy for HER2-overexpressing cancers, overcoming the limitations of trastuzumab.

Integrative analysis demonstrated that Med23 modulates the P300 binding to Sp1-targeted genes, thus orchestrating the H3K27 acetylation and enhancer activation for the oligodendrocyte lineage progression. Collectively, our findings identified the critical role for the Mediator Med23 in oligodendrocyte fate determination and provide mechanistic insights into the myelination pathogenesis associated with MED23 mutations.

Subsequently, NUPR1, a transcriptional cofactor known to induce premature senescence in lung cancer cells by disrupting autophagic processes, was validated as a downstream target of the MED23/BCLAF1 complex through RNA-seq and ChIP assays. Thus, the interaction between MED23 and BCLAF1 regulates NUPR1 expression, impacting autophagic flux and leading to premature senescence in NSCLC cells.

The KATP channels are effective in the M1 AQP4-tetramer and M23 AQP4-OAP cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramer cell phenotypes inhibiting KATP channels and inducing early apoptosis.

Disruption of GAS41-H3K27ac/cr binding caused BRD2, MED14 and MED23 to dissociate from gene loci, leading to nuclear shape abnormalities. Overall, our findings demonstrate that GAS41 collaborates with BRD2 and the Mediator complex to control the expression of crucial nuclear shape regulators.

The germline variant FH: p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of FH-related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL.

Collectively, these findings revealed that MED23 may negatively regulate Kras-induced lung tumourigenesis in vivo, which would improve the precise classification of KRAS-mutant lung cancer patients and provide new insights for clinical interventions.