CDKN2AIP-induced cell senescence and apoptosis of testicular seminoma are associated with CARM1 and eIF4β  

作　　者：Yuming Cao Zhenlie Chen Zihan Qin Kaiyu Qian Tongzu Liu Yuanzhen Zhang 

机构地区：[1]Department of Gynaecology and Obstetrics,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [2]Clinical Medicine Research Center for Prenatal Diagnosis and Birth Health,Wuhan 430071,China [3]Department of Biological Repositories,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [4]Urology Surgery,Zhongnan Hospital of Wuhan University,Wuhan 430071,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第5期604-614,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grant from the National Natural Science Foundation of China(No.81771543).

摘　　要：Testicular seminoma is a relatively rare tumor which is mostly detected in male population aged from 15 to 35 yearsold. Although several molecular biomarkers have been identified to be associated with testicular seminoma pathogenesis, the exact mechanism for testicular seminoma progression remains largely unknown. CDKN2A interacting protein (CDKN2AIP) has previously been identified as a tumor suppressor in multiple malignant diseases. Inthis study, we aimed to further explore its role in testicular seminoma as well as the underlying molecular mechanisms. Retrospective testicular seminoma clinical samples, normal tissues, NTERA-2 cell line, and mouse xenograft models were used in this study. RT-qPCR, western blot analysis, immunofluorescence microscopy, Co-IPand IP-MS experiments were performed to detect the expression of CDKN2AIP and its interaction with CARM1 andeIF4β. SA-β-gal staining assay and H3K9me3 activity experiments were used to subsequently evaluate the cellsenescence and apoptosis. Mouse xenograft animal model was used for in vivo study. The results showed thatCDKN2AIP is highly expressed in normal testis samples, and is significantly suppressed in testicular seminomaclinical samples and cell line model. Up-regulation of CDKN2AIP is significantly associated with the inhibition oftesticular seminoma tumor growth and the increase of cell senescence and apoptosis. CDKN2AIP exhibits antitumor activity by interacting with CARM1 and eIF4β. CDKN2AIP induces testicular seminoma cell senescence bysuppressing CARM1 expression and eIF4β phosphorylation. The CDKN2AIP-CARM1 and CDKN2AIP-eIF4β interactions, which induce tumor cell senescence and apoptosis, may be the potential druggable molecular pathways intesticular seminoma tumor pathogenesis and progression.

关 键 词：CDKN2AIP CARM1 eIF4β SEMINOMA SENESCENCE APOPTOSIS 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学]