PIAS4 (Protein Inhibitor Of Activated STAT 4)

P=N/A, N=20, Not yet recruiting, Ningbo Medical Centre Lihuili Hospital; Ningbo Medical Centre Lihuili Hospital

PIAS4 expression level plays a role in breast cancer cell survival, invasiveness, and chemoresistance, partly by altering anti-apoptotic pathways. These findings position PIAS4 as a potential biomarker and therapeutic target for overcoming resistance to anthracycline-based therapies in breast cancer.

This study, to our knowledge, is the largest pretreatment autoantibody screen in melanoma immunotherapy, demonstrates that serum autoantibody profiles can stratify patients at risk for irAEs and ir-colitis. The identified signatures connect tumor-related and immunity-related antigens, stress-response pathways, and autoimmune mechanisms. Pretreatment autoantibody profiling offers a promising biomarker-driven approach for individualizing risk assessment, improving patient selection, and guiding early intervention strategies to enhance the safety of immune checkpoint blockade in melanoma. Beyond toxicity prediction, our findings also suggest that specific autoantibodies may reflect underlying immune activation states linked to therapeutic response.

Functional assays demonstrated that USP1 overexpression promotes aggressive phenotypes in HCC cells, including enhanced proliferation, migration, and epithelial-mesenchymal transition (EMT), whereas USP1 inhibitor ML323 suppresses these effects and increases sensitivity to oxaliplatin and fluorouracil (5-FU), the primary agents in FOLFOX, both in vitro and in vivo...Importantly, inhibition of SUMOylation significantly attenuated the aggressive effects mediated by USP1. In conclusion, this study highlights the USP1/PIAS1/HELLS deubiquitinating and SUMOylation axis as a critical driver of aggressiveness and DNA damage repair responses in HCC cells, offering a promising therapeutic strategy to suppress HCC progression and enhance the efficacy of FOLFOX-based chemotherapy.

Collectively, our study not only provides a powerful prognostic tool but also identifies a promising multi-target natural compound, offering a novel strategy to overcome chemoresistance in PAAD.

6-MF targets PTBP1 to inhibit circPIAS1 biogenesis and reduce circPIAS1-108aa.6-MF inhibits PI3K-AKT pathway; combined with IFN-γ, it enhances STAT1 phosphorylation, inhibits SLC7A11/GPX4 pathway, promoting melanoma ferroptosis. Its combination with PD-1 inhibitor enhances antitumor efficacy, providing a novel therapeutic strategy for melanoma treatment.

These findings contribute to the understanding of PIAS family genes in HNSC pathogenesis, diagnosis, prognosis, and potential therapeutic targeting.

This study is the first to identify differentially perturbed immune and inflammatory signaling pathways that were associated with symptom burden in oncology patients receiving chemotherapy. Evaluation of interventions targeted at the cytokine-cytokine receptor interaction and endocytosis pathways may decrease the burden associated with single and multiple occurring symptoms.

This study provides valuable insights into the multifaceted roles of PIAS family genes in LIHC pathogenesis and paves the way for personalized diagnostic and therapeutic interventions.

Furthermore, this study identified a compound, LZQ-02-023-01, which effectively induces the METTL10-mediated ubiquitination and degradation of MITF, thereby reducing the oncogenic activity of METTL10. The findings suggest that METTL10 plays an important role in reprogramming purine metabolism, which promotes GC, highlighting it as a potential therapeutic target for GC treatment.

PIAS1 expression in stromal and immune cells is associated with tumor-suppressive reprogramming of the OSCC microenvironment. These findings position PIAS1 as a potential modulator of anti-tumor immunity and candidate target for therapeutic intervention.

Results obtained by immunohistochemical analysis of GRHL2 expression in primary breast cancers support an important role of GRHL2 subnuclear compartmentalization in breast carcinogenesis. Taken together, our results provide new insights into complex regulatory mechanisms governing GRHL2 activity in cancer cells.