翌圣生物 Yeasen｜生命科学试剂与诊断原料一站式平台

Abstract

Testicular cancer is the most common malignancy in young men, and treatment options for metastatic or refractory disease remain limited. Chromatin remodeling plays a critical role in tumorigenesis, yet its contribution to testicular cancer progression is poorly understood. This study aimed to elucidate the oncogenic and epigenetic functions of chromodomain helicase DNA-binding protein 1-like (CHD1L) in testicular cancer. Immunohistochemistry and TCGA transcriptomic analyses were performed to assess CHD1L expression and clinical relevance. Functional assays, RNA sequencing, and ATAC-seq were conducted to explore its biological effects and regulatory mechanisms. In vivo xenograft models were used to validate tumor-promoting activity. CHD1L was markedly overexpressed in testicular cancer tissues and correlated with advanced pathological stage. High CHD1L expression was correlated with immune-infiltration patterns indicative of immune exclusion, including increased Treg/Th2 signatures and reduced cytotoxic T-cell activity based on TCGA analyses. Functional studies revealed that CHD1L enhanced cell proliferation, migration, and invasion both in vitro and in vivo. Integrative multi-omics analyses identified CXCR6 as a direct downstream effector of CHD1L. Mechanistically, CHD1L promoted CXCR6 transcription through H3K9me3 demethylation, thereby activating the PI3K/AKT signaling pathway. CHD1L drives testicular cancer progression through epigenetic activation of the CXCR6/PI3K/AKT axis and immune modulation. These findings highlight CHD1L as a potential therapeutic target for advanced or treatment-resistant testicular cancer.