PRKD1 (Protein Kinase D1)

ARID1A-KO also reduced HLA-related protein expression and enhanced extracellular matrix components, potentially limiting immune infiltration and immunotherapy efficacy. Our multi-omics analysis revealed PRKD1, JUN, and NCK1 as key resistance nodes, offering potential targets for therapeutic strategies to counter resistance in melanoma.

With respect to drug response, PRKD1-high HCC cases exhibited increased predicted sensitivity to multiple tyrosine kinase inhibitors (TKIs), while in vitro PRKD1 knockdown reduced sorafenib sensitivity, and sorafenib treatment suppressed both PRKD1 and p-ERK1/2 levels. Collectively, our findings identify PRKD1 as a multifaceted contributor to HCC progression, immune microenvironment modulation, and TKI responsiveness. These results highlight PRKD1 as a promising therapeutic target warranting further mechanistic and translational investigation.

The shortened tail and increased fat accumulation represent key adaptations for thermoregulation and energy conservation in high-latitude habitats. Notably, all Tibetan macaque populations experienced long-term selection pressures from cold at high latitudes, which have not only shaped distinctive adaptive traits, but may also render the species particularly vulnerable to contemporary climate warming, particularly for the eastern populations.

P=N/A, N=30, Not yet recruiting, Loma Linda University | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: Jul 2026 --> Dec 2026

These findings highlight PKD isoforms as potential therapeutic targets, particularly in cancer settings where metabolic dysfunction plays a contributing role. While current PKD inhibitors lack isoform specificity, future therapeutic strategies focused on PKD2 and PKD3 modulation may offer selective control over invasion, immune evasion, and metabolic reprogramming in metabolically comorbid cancer patients.

Loss of Snhg5 did not attenuate cyst formation; if anything, disease severity was mildly but not significantly exacerbated. These findings indicate that Snhg5 modulates cell-cycle control and is dispensable for kidney development and cystogenesis in collecting duct-derived cysts.

Third, it integrates translational insights rarely synthesized in prior work: mapping natural compounds (icariin II and artesunate), repurposed drugs (sorafenib and melatonin), and novel modulators to disease stages (e.g., Lip-1 for fibrosis and salinomycin for RCC stem cells); highlighting strategies to reverse ferroptosis-related drug resistance (targeting DPP9 in RCC); and identifying ferroptosis-related genes (ACSL4 and PDIA4) as prognostic biomarkers. This review not only synthesizes ferroptosis pathophysiology and research advances but also delineates disease-tailored therapeutic strategies. By addressing key knowledge gaps-crosstalk between ferroptosis and other cell death modalities (e.g., pyroptosis), lack of kidney-specific clinical biomarkers, and underexplored roles in autoimmune nephritides-it provides a conceptual roadmap for mechanism-based diagnostics, precision therapeutics, and rational drug combinations, transcending traditional disease boundaries to advance clinical translation for both primary and secondary kidney diseases.

Overall, CBX8 phosphorylation by PKD1 impaired PRC1 complex integrity and activity, mitigated H2AK119ub1 level, caused the upregulation of multiple target genes repressed by CBX8, and decreased CBX8, H2AK119ub1, and H3K27me3 enrichment at INK4A/ARF locus, thereby derepressing p16INK4A and facilitating cellular senescence. Collectively, these results suggest that PKD1-mediated CBX8 phosphorylation at T234 and S256/311 is a key mechanism governing CBX8 function, including cell senescence.

This neoplasm showed typical morphology with nests of tumor cells with cribriform and papillary architecture and a classic immunohistochemical profile with tumor cells positive for S100 and p63 while negative for p40. Molecular studies showed a NAP1L1::PRKD1 fusion, which has not been previously detected in cribriform adenocarcinoma.

A genotype-first ascertainment of individuals in genomic research allows for a more comprehensive assessment of Mendelian disease and removes biases that confound our understanding of the penetrance and presentation of these conditions.