High KAP1 expression promotes pleural mesothelioma cell proliferation and metastasis

PurposeThis study aimed to investigate KRAB-associated protein 1 (KAP1) expression in pleural mesothelioma (PM) and its impact on the biological behavior of the human pleural mesothelioma cell line MSTO-211H, providing a specific biomarker for the early clinical diagnosis of PM.Patients and methodsKAP1 expression levels in PM tissues were detected using immunohistochemistry. Lentivirus infection was used to construct MSTO-211H mesothelioma cell lines with stable KAP1 overexpression or knockdown, and the efficiency of KAP1 overexpression or knockdown was detected using qRT-PCR(quantitative Reverse Transcription PCR) and Western blotting. The effects of KAP1 overexpression and knockdown on MSTO-211H mesothelioma cell proliferation, migration, and invasion were detected using cell counting kit-8, plate colony formation, cell scratch, and transwell invasion assays, respectively. The effects of KAP1 overexpression and knockdown on the cell cycle, related cyclins, and apoptosis were detected using flow cytometry. Gene enrichment and correlation analysis of mesothelioma were performed using bioinformatics analysis.ResultsKAP1 was significantly overexpressed in PM tissues compared with normal pleural tissues (P < 0.05). Compared to the control group, KAP1 overexpression in mesothelioma MSTO-211H cells significantly enhanced proliferation, migration, and invasion (P < 0.05), without causing cell cycle arrest, and significantly increased the mRNA and protein levels of cyclin D1 and cyclin E (P < 0.05), whereas the apoptosis rate did not significantly change (P > 0.05). Conversely, KAP1 knockdown in mesothelioma MSTO-211H cells significantly inhibited their proliferation, migration, and invasion abilities (P < 0.05), induced G0/G1 phase arrest in the cell cycle, and significantly increased the apoptosis rate (P < 0.05). Spearman correlation analysis revealed significant positive associations between KAP1 mRNA expression and TP53 and SHOX2. Conversely, KAP1 expression was significantly negatively correlated with MTAP and MSLN. GSEA reveals KAP1-associated enrichment of DNA repair, cell cycle, and proteostasis pathways in TCGA-MESO.ConclusionKAP1 is highly expressed in PM and functions as an oncogene-like regulator, enhancing tumor cell growth and aggressiveness.Clinical trial registration2023-28.