Abstract

Background The role of KMT5C varies across different tumor types, while its expression and function in prostate cancer remain largely unreported. This study investigated KMT5C expression in prostate cancer and its effects on tumor growth and immune response. Methods Following KMT5C knockdown and overexpression, we evaluated cell proliferation, cell cycle distribution and angiogenesis, and detected the activation of FGFR1/STAT3 pathway via Western blot. The molecular interaction between KMT5C and FGFR1 was bioinformatically predicted and experimentally validated. Subcutaneous xenograft models in nude and C57BL/6 mice were constructed to explore the effects of KMT5C on prostate cancer progression and tumor immune regulation. Result Our findings showed that KMT5C was highly expressed in prostate cancer and functions as an oncogene to facilitate cell proliferation, angiogenesis, and G0/G1-to-S cell cycle transition. Conversely, KMT5C knockdown suppressed cell proliferation, angiogenesis and arrested the G0/G1/S phase transition. Mechanistically, the oncogenic properties of KMT5C were partially dependent on the activation of FGFR1/STAT3 signaling pathway. KMT5C depletion increased the proportion of CD8+ T cells in the spleen and elevated the infiltration of CD8+ cytotoxic T lymphocytes within the tumor microenvironment.. Moreover, KMT5C silencing induced the polarization of tumor-associated macrophages (TAMs) from the M2-like immunosuppressive phenotype to the M1-like anti-tumor phenotype. Conclusion KMT5C acts as a critical oncogenic driver in prostate cancer, which is closely associated with tumor malignancy and tumor immune homeostasis. Thus, KMT5C may serve as a promising therapeutic target for prostate cancer intervention. Collectively, our findings provide solid experimental evidence for the clinical relevance of KMT5C.