CDKN2AIP Induces Cellular Senescence and Apoptosis of Testicular Seminoma Tumor by Interacting with CARM1 and eIF4B

Abstract BackgroundTesticular seminoma are relatively rare tumors, which are mostly detected in male population aged between 15 to 44 years old. Although previous researches identified several molecular biomarkers associated with testicular seminoma pathogenesis, the exact mechanism for testicular seminoma progression remains largely unknown. CDKN2AIP has been previously indicated as tumor suppressor in multiple malignant diseases, in this study we aimed to further discover its role in testicular seminoma and underlying molecular mechanismsMethodsRetrospectively collected testicular seminoma clinical samples and normal tissues combined with NTERA-2 cell line models, as well as mice xenograft models were utilized for this study. CDKN2AIP expression and its interaction with CARM1 and eIF4B were detected by qRT-PCR, western blot, immunofluorescence assay combined with Co-IP and IP-MS experiments. Cellular senescence and apoptosis were subsequently evaluated via SA-beta-gal staining assay and H3K9me3 activity experiments. Mice xenograft animal model was used for in-vivo validation studyResultsCDKN2AIP was highly-expressed in normal testis samples, and was significantly suppressed in testicular seminoma clinical samples and cell line models. Up-regulation of CDKN2AIP was significantly associated with inhibited testicular seminoma tumor growth and increased cellular senescence and apoptosis. Further experiments demonstrated CDKN2AIP exhibited anti-tumor activity via interaction with CARM and eIF4ConclusionCDKN2AIP induced testicular seminoma cellular senescence by suppressing CARM1 expression and eIF4B phosphorylation. CDKN2AIP-CARM1 and CDKN2AIP-eIF4B interaction-induced tumor cell senescence and apoptosis might be potential druggable molecular pathway in testicular seminoma tumor pathogenesis and progression