Silencing of PODXL2 Modulates Cell Viability and Tumor Immune Microenvironment of Prostate Cancer and Involves PI3K/AKT Pathway Inactivation

Abstract

Prostate cancer (PCa) is one of the malignant tumors affecting men and is an important reason for the increase in male mortality worldwide. The pathogenesis of PCa is not fully understood. Thus, there is an urgent need to discover novel therapeutic targets to facilitate the development of effective anti-PCa strategies. Quantitative real-time PCR and Western blot were applied to detect the PODXL2 expressions in PCa tissues and cells. Progression-free survival of PCa patients was assessed using Kaplan–Meier survival analysis. The relevance between PODXL2 expressions and PCa clinical index was assessed with a Chi-square test. Cell infection, cell coculture system, Cell Counting Kit-8 assay, TUNEL staining, Transwell, analysis of PCa cell epithelial-mesenchymal transition (EMT) morphological changes, flow cytometry, and enzyme-linked immunosorbent assay were used for the analysis of PODXL2 functions in PCa. Meanwhile, the PODXL2 mechanism in PCa was dissected via Western blot, immunofluorescence analysis, Cell Counting Kit-8 assay, Transwell, and flow cytometry. Furthermore, PODXL2 impacts in PCa growth were examined in vivo using TUNEL staining, immunohistochemistry, and Western blot. PODXL2 expressions were raised in PCa tissues and cells, and PCa patients with high PODXL2 expressions owned poorer progression-free survival, and PODXL2 was interrelated to the TNM stage and distant metastasis of PCa. Interference with PODXL2 weakened PCa cell proliferation, invasion, EMT, and immune escape, while promoting PCa cell apoptosis. Furthermore, silencing PODXL2 reduced PCa cell proliferation, invasion, EMT, immune escape, and boosted cell apoptosis, which involved PI3K/AKT pathway inactivation. Meanwhile, PODXL2 knockdown reduced the tumor weight of PCa and promoted apoptosis in vivo. Interference with PODXL2 inhibited PCa cell proliferation, invasion, EMT, immune escape, enhanced cell apoptosis, and involved PI3K/AKT pathway inactivation.