Background: Cancer-associated fibroblasts (CAFs) are an important part of the tumour microenvironment, and their functions are of great concern. This series of experiments aimed to explore how Yes-associated protein 1 (YAP1) regulates the function of stromal cells and how the normal fibroblasts (NFs) convert into CAFs in prostate cancer (PCa). Methods: The effects of conditioned media from different fibroblasts on the proliferation and invasion of epithelial cells TrampC1 were examined. We then analysed the interaction between the YAP1/TEAD1 protein complex and SRC, as well as the regulatory function of the downstream cytoskeletal proteins and actins. A transplanted tumour model was used to explore the function of YAP1 in regulating tumour growth through stromal cells. The relationship between the expression of YAP1 in tumour stromal cells and the clinical characteristics of PCa patients was analysed. Results: The expression level of YAP1 was significantly upregulated in PCa stromal cells. After the expression level of YAP1 was increased, NF was transformed into CAF, enhancing the proliferation and invasion ability of epithelial cells. The YAP1/TEAD1 protein complex had the capability to influence downstream cytoskeletal proteins by regulating SRC transcription; therefore, it converts NF to CAF, and CAF can significantly promote tumour growth and metastasis. The high expression of YAP1 in the tumour stromal cells suggested a poor tumour stage and prognosis in PCa patients. Conclusion: YAP1 can convert NFs into CAFs in the tumour microenvironment of PCa, thus promoting the development and metastasis of PCa. Silencing YAP1 in tumour stromal cells can effectively inhibit tumour growth.

Background: N7-methylguanosine (m7G) modification is, a more common epigenetic modification in addition to m6A modification, mainly found in mRNA capsids, mRNA interiors, transfer RNA (tRNA), pri-miRNA, and ribosomal RNA (rRNA). It has been found that m7G modifications play an important role in mRNA transcription, tRNA stability, rRNA processing maturation, and miRNA biosynthesis. However, the role of m7G modifications within mRNA and its “writer” methyltransferase 1(METTL1) in tumors, particularly prostate cancer (PCa), has not been revealed. Methods: The differential expression level of METTL1 between hormone-sensitive prostate cancer (HSPC) and castrate-resistant prostate cancer (CRPC) was evaluated via RNA-seq and in vitro experiments. The effects of METTL1 on CRPC progression were investigated through in vitro and in vivo assays. The upstream molecular mechanism of METTL1 expression upregulation and the downstream mechanism of its action were explored via Chromatin Immunoprecipitation quantitative reverse transcription polymerase chain reaction (CHIP-qPCR), Co-immunoprecipitation (Co-IP), luciferase reporter assay, transcriptome-sequencing, m7G AlkAniline-Seq, and mRNA degradation experiments, etc. Results and conclusion: Here, we found that METTL1 was elevated in CRPC and that patients with METTL1 elevation tended to have a poor prognosis. Functionally, the knockdown of METTL1 in CRPC cells significantly limited cell proliferation and invasive capacity. Mechanistically, we unveiled that P300 can form a complex with SP1 and bind to the promoter region of the METTL1 gene via SP1, thereby mediating METTL1 transcriptional upregulation in CRPC. Subsequently, our findings indicated that METTL1 leads to enhanced mRNA stability of CDK14 by adding m7G modifications inside its mRNA, ultimately promoting CRPC progression.

Background Dendritic cells (DCs) derived extracellular vesicles represent a promising vehicle for the activation of adaptive immunity, demonstrating significant potential in the development of cancer nanovaccines. The aim of this study was to evaluate the antitumor efficacy of a functional DCs-derived extracellular vesicles in castration-resistant prostate cancer. Methods A pre-modification strategy was employed to overexpress XCL1 in dendritic cells, enabling their extracellular vesicles to highly express XCL1 protein. In vitro experiments, prostate cancer-bearing mouse models, and OVA-expressing prostate cancer mouse models demonstrated that dendritic cells efficiently internalize extracellular vesicles derived from XCL1-overexpressing mature dendritic cells (DEX_XCL1), thereby enhancing the chemotaxis, activation, and antigen-presenting capacity of cDC1 cells. When combined with the immunogenic cell death effect induced by cisplatin, this approach significantly increased the number and cytotoxic activity of CD8⁺ T cells, improved the tumor microenvironment, and effectively suppressed prostate cancer tumor growth. Results The coding sequence of XCL1 successfully inserted upstream of the PDGFR transmembrane domain and transfected into dendritic cells, enabling their extracellular vesicles to highly express XCL1 protein. Extracellular vesicles derived from XCL1-overexpressing mature dendritic cells not only exhibited high XCL1 expression, but were also enriched with chemokine receptor CCR7 and MHC I molecules on their surface. This nanovaccines enhanced the uptake of extracellular vesicles by dendritic cells, recruited cDC1 cells within the tumor tissue, and significantly improved their antigen-presenting capacity. When combined with the immunogenic cell death effect induced by cisplatin, which generates a large amount of tumor-associated antigen STEAP1, this strategy effectively enhanced the proliferation and cytotoxic activity of CD8⁺T cells. Moreover, it reduced the proportion of regulatory T cells and immunosuppressive factors, thereby reshaping the tumor immune microenvironment. This approach effectively inhibited tumor growth in mice and prolonged their survival. These findings demonstrate the strong synergistic effects of the nanovaccines and cisplatin in promoting antitumor immunity. Conclusions A novel nanovaccines induces potent antitumor immune responses and, in combination with the chemotherapeutic agent cisplatin, effectively remodels the tumor immune microenvironment. This approach offers a new strategy and preclinical evidence for the immunotherapy of “cold tumors” prostate cancer.

Matrix Metalloproteinases (MMPs) have been demonstrated to be essential in facilitating the migration and metastasis of clear cell renal cell carcinoma (ccRCC). However, the ability of the MMP family to predict clinical outcomes and guide optimal therapeutic strategies for ccRCC patients remains incompletely understood. In this investigation, we initially conducted a thorough examination of the MMP family in pan-cancer. Notably, MMPs exhibited distinctive significance in ccRCC. Following this, we undertook an extensive analysis to evaluate the clinical value of MMPs and potential mechanisms by which MMPs contribute to the progression of ccRCC. A novel stratification method and prognostic model were developed based on MMPs in order to enhance the accuracy of prognosis prediction for ccRCC patients and facilitate personalized treatment. By conducting multi-omics analysis and transcriptional regulation analysis, it was hypothesized that SAA1 plays a crucial role in promoting ccRCC migration through MMPs. Subsequently, in vitro experiments confirmed that SAA1 regulates ccRCC cell migration via the ERK-AP1-MMPs axis. In conclusion, our study has explored the potential value of the MMP family as prognostic markers for ccRCC and as guides for medication regimens. Additionally, we have identified SAA1 as a crucial factor in the migration of ccRCC.

Background: The six‐transmembrane epithelial antigen of the prostate 3 (STEAP3) is a metalloreductase, which is essential for iron uptake. Existing literature has shown that STEAP3 may perform an important role in the onset and progression of tumors. Nonetheless, a complete pan‐cancer investigation of the prognostic significance and immune properties of STEAP3 is currently unavailable.Aims: As part of our investigation into the possible functions of STEAP3 in malignancies, we conducted a comprehensive analysis to examine the prognostic value and immune features of STEAP3 in human pan‐cancer.Methods and Results: R and Cytoscape programs were applied to analyze and visualize the data. The expression of STEAP3 in both cell lines and tissues was measured utilizing a variety of approaches. Using the shRNA knockdown technique, we tested the viability of the A498 and 786‐O cell lines and validated their functions. Both CCK‐8 and transwell assays were conducted to estimate cell proliferation and invasion. The expression of STEAP3 was substantially elevated and was shown to be linked to prognosis in the majority of malignancies, notably in clear cell renal cell carcinoma (ccRCC). In addition, the expression of STEAP3 was shown to have a strong correlation with immune infiltrates, which in turn triggered the recruitment and polarization of M2 macrophages in ccRCC. The protein STEAP3 shows promise as a predictor of responses to immune‐checkpoint blockade (ICB) therapy. Positive links between STEAP3 and the epithelial‐mesenchymal transition (EMT), the p53 pathway, and the immune‐associated pathways were also found in the enrichment analysis. Our results illustrated that the STEAP3 expression level was substantially elevated in ccRCC tissues and suggested that it could stimulate EMT in ccRCC by downregulating CDH1.Conclusion: In a diverse range of cancers, STEAP3 might serve as a biomarker for determining the prognosis as well as a predictor of immunotherapy responsiveness. STEAP3 is a novel biological marker for determining prognosis, and it also performs a remarkable function in the promotion of tumor growth in ccRCC by enhancing invasion and EMT, as well as by triggering the recruitment and polarization of M2 macrophages.

Metastasis is the leading cause of death in clear cell renal cell carcinoma (ccRCC) patients. Anoikis, a form of programmed cell death induced by the loss