Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer. Patients with TNBC have poor clinical outcome as they are non-responsive to current targeted therapies. There is an urgent need to identify new therapeutic targets and develop more effective treatment options for TNBC patients. Osthole, a natural product from C. monnieri, has been shown to inhibit certain cancer cells. However, the mechanisms of action as well as its effect on TNBC cells are not currently known. We investigated the effect of osthole in cultured TNBC cells as well as in a xenograft model of TNBC growth. We also used a high-throughput proteomics platform to identify the direct binding protein of osthole. We found that osthole inhibited the growth of a panel of TNBC cells and induced apoptosis in both cultured cells and TNBC xenografts. We used a high-throughput proteomics platform and identified signal transducer and activator of transcription 3 (STAT3) as a potential binding protein of osthole. We further show that osthole suppressed STAT3 in TNBC cells to inhibit growth and induce apoptosis. Overexpressing STAT3 in TNBC reduced the effectiveness of osthole treatment. These results provide support for osthole as a potential new therapeutic agent for the management of TNBC. Moreover, our results indicate that STAT3 may be targeted for the development of novel anti-TNBC drugs.

In this study, we aimed to clarify the role of PIM-1 in papillary thyroid carcinoma (PTC) in vitro and investigate the relationship between PIM-1 and redox proteins (NOX4, SOD2, and GPX2) at the tissue and cellular levels. As a PIM-1 inhibitor, SGI-1776 inhibited cell proliferation, colony formation, migration and induced an increase in apoptosis and reactive oxygen species in two PTC cell lines (BCPAP and TPC-1). The expressions of PIM-1, SOD2 and GPX2 were downregulated after siNOX4 exposure. Immunohistochemistry in 120 PTC patients showed that all four proteins exhibited higher expression levels in PTC tissues than in adjacent normal tissues. PIM-1 expression was related to NOX4, SOD2, and GPX2 expressions. The Cancer Genome Atlas database analysis showed the significant correlation between the expression of NOX4 and PIM-1. Our results demonstrated that PIM-1 played an important oncogenic role in PTC carcinogenesis that may be related to oxidative stress.

Purpose RNF213 encodes one of the largest E3 ubiquitin ligases in the human proteome, playing essential roles in ubiquitination, DNA damage repair, and immune system regulation. Although RNF213 has been extensively studied in Moyamoya disease, its involvement in cancer biology remains insufficiently understood. This study seeks to conduct a comprehensive pan-cancer analysis to explore RNF213 expression, mutation characteristics, its correlation with clinical outcomes, and its potential as a prognostic biomarker and a therapeutic target, particularly in the context of immunotherapy. Methods Leveraging data from The Cancer Genome Atlas (TCGA) and additional publicly available datasets, we performed a systematic analysis of RNF213 expression patterns, mutation frequencies, and their relationships with clinical outcomes. We also conducted survival analyses to assess the impact of RNF213 expression on the efficacy of immune checkpoint blockade therapies. Results RNF213 demonstrated variable expression levels across different cancer types, with notable overexpression observed in glioblastoma and endometrial carcinoma, while underexpression was detected in lung adenocarcinoma and prostate adenocarcinoma. Elevated RNF213 expression was linked to unfavorable survival outcomes in acute myeloid leukemia and low-grade glioma, whereas it was associated with better survival in sarcoma and skin cutaneous melanoma. RNF213 expression showed a positive association with immune-related genes and immune cell infiltration, particularly in glioblastoma and breast cancer. Furthermore, patients with high RNF213 expression experienced significant survival advantages when receiving combined anti-PD-1 and anti-CTLA-4 immunotherapies. Conclusion This study highlights RNF213’s dual functionality in tumor progression and immune modulation, underscoring its potential as both a prognostic biomarker and a therapeutic target. The findings suggest that RNF213 may play a pivotal role in determining immunotherapy outcomes, warranting further exploration into its underlying mechanisms and clinical applications.