E2F1-mediated PKMYT1 upregulation promotes prostate cancer progression by inhibiting the PPAR signaling pathway

作者：Zengshun Kou, Yu Wang, Jiaxi Zhu, Shuaizhi Zhu, Zhibo Si, Hai Zhu · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-32218-0 · 研究领域：Ferroptosis and cancer prognosis、Prostate Cancer Treatment and Research、Peroxisome Proliferator-Activated Receptors

Protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) is a protein-coding gene associated with cell cycle regulation and cancer development, but its specific mechanism in prostate cancer (PCa) has not been clarified. This study sought to elucidate the role of PKMYT1 in PCa. Expression patterns, prognostic significance and potential mechanisms of PKMYT1 were explored by the TCGA database. Single-cell sequencing was performed using the GSE137829 dataset. Multi-database prediction identified potential transcription factors regulating PKMYT1 expression. PC3 cell line with PKMYT1 knockdown was established. Functional analyses (CCK-8, Wound healing, and Transwell assays) were performed to investigate the changes in tumor malignant behavior after PKMYT1 silencing. Western blot experiments were performed to analyze the effects of PKMYT1 on epithelial-mesenchymal transition (EMT) and PPAR signaling pathway. PKMYT1 was overexpressed in prostate cancer samples and its high expression was significantly associated with poor prognosis and Th2 cell infiltration. Knockdown of PKMYT1 could effectively inhibit the proliferation, migration, and EMT process of PCa cells. Mechanistically, E2F1 is an important factor regulating PKMYT1 expression, and PKMYT1 could inhibit the activity of the PPAR signaling pathway, thus ensuring the reinforcement of PCa progression. PKMYT1 can accelerate the progression of PCa by regulating the cell cycle, EMT process and PPAR signaling pathway. Targetin...