SPI1 (Spi-1 Proto-Oncogene)

Collectively, our findings suggest that SPI1 palmitoylation inhibits c-CBL-mediated ubiquitination and degradation, thereby enhancing SPI1 protein stability and its transcriptional regulation of miR-205-5p. Upregulated miR-205-5p in NPC cells is packaged into exosomes and transferred to endothelial cells, where it targets and inhibits WWC2 expression, eventually promoting angiogenesis and NPC radioresistance.

CCDC86 acts as a key regulator of immune communication in HNSCC, orchestrating APC-T cell interactions and shaping an immunoregulatory niche. By linking antigen presentation with checkpoint signaling, CCDC86 contributes to immune evasion while maintaining local immune activation. These findings highlight CCDC86 as a promising prognostic biomarker and potential immunotherapeutic target in HNSCC.

Its high expression integrates tumor-intrinsic programs (cell cycle, EMT, hypoxia) with tumor-extrinsic immune activation, predicts differential drug sensitivities, and outperforms established biomarkers in forecasting response to immune-checkpoint blockade-particularly in MSI-high disease. These findings nominate IFI30 as a promising diagnostic marker and therapeutic target.

This study provided translational insights, enhancing the current understanding of testicular pathogenesis and contributing to the diagnosis and treatment of cryptorchidism.

In the context of cancer biology, VIM-AS1 did not affect the antiproliferative actions of TGF-β, yet had an impact on the epithelial-mesenchymal transition gene program, and increased the invasion and motility of tumor cells, whereas its silencing sensitized cancer cells to chemotherapeutic agents. The molecular mechanism highlights how a lncRNA can modulate the nuclear pore's capacity to import SMAD complexes, by facilitating their capture by Nup358/RanBP2 and thereby enhancing nuclear accumulation of SMADs with distinct isoform composition, thus promoting selectively TGF-β signaling responses.

We have reported that EETs inhibit AEC senescence, alleviating bleomycin (BLM)-induced PF in mice...Inhibition of Spi1 significantly attenuated AEC senescence. Inhibition of Spi1 alleviated pulmonary fibrosis in aging mice.

Blockade of SPI1 effectively prevents colitis-induced S100A8/A9 upregulation in macrophages. Thus, our findings highlight the potential link between ADAP and intestinal inflammation, while also paving the way for therapeutic interventions targeting the ADAP-SPI1-S100A8/A9 signaling axis in inflammatory colitis.

This promotes epigenetic up-regulation of c-Myc by reducing H3K27 trimethylation. Together, these findings demonstrate the critical role of USP30-AS1 in breast cancer progression through HnRNPF/p21 and EZH2/c-Myc/p21 axes, highlighting its potential as a therapeutic target for breast cancer treatment.

The developed model with high predictive performance and the predicted TFs with DNA-demethylation-promoting activity will be useful for further analysis of TFs involved in generation of DNA methylation profiles in normal cell development and disease.

In conclusion, circNEIL3 stabilizes SPI1 mRNA expression by binding to U2AF2, thereby promoting glioma progression and temozolomide resistance. Implications: Our findings offer a new mechanistic insights into gliomas drug resistance, and targeting the circNEIL3/U2AF2/SPI1 axis represents a promising approach to counteract TMZ resistance in gliomas.

Mechanistically, SPI1 transcriptionally suppresses ACSL4 expression through the EZH2/H3K27me3 pathway, leading to inhibition of intracellular lipid peroxidation. Thus, SPI1 knockdown synergizes with erastin to promote lipid peroxidation and ferroptosis, suggesting that targeting SPI1 may represent a promising therapeutic strategy for renal cell carcinoma.

This study novelly suggests ZEB2 as a transcription factor that promotes TREM2 expression. Further investigation into the role of ZEB2 in various TREM2-associated diseases is warranted.