RETRACTED: SPAG6 hypermethylation silences a novel tumor suppressor and inhibits renal cell carcinoma progression via PI3K/AKT/mTOR pathway

作者：Tianyu Wu, Xing Ji, Yongyang Yun, Xiao‐Fei Wang, Ying Gan, Fan Yu, Qian Zhang · 发表于：PLoS ONE · 年份：2025 · DOI：10.1371/journal.pone.0333202 · 被引用次数：2 · 研究领域：Epigenetics and DNA Methylation、Ferroptosis and cancer prognosis、Renal and related cancers

BACKGROUND: Renal cell carcinoma (RCC) ranks among the most prevalent malignancies of the genitourinary system, with a steadily rising incidence. Despite growing attention, the etiology and underlying mechanisms of RCC remain incompletely understood. Epigenetic modifications, particularly DNA methylation, have emerged as critical regulators in various malignancies, including RCC. Sperm-associated antigen 6 (SPAG6), initially identified in human testicular tissue and considered a marker for testicular tumors, has been associated with the pathophysiology of several malignancies. This study aimed to elucidate the role of aberrant SPAG6 methylation in RCC progression. METHODS: We first analyzed SPAG6 expression and methylation patterns in RCC and adjacent normal tissues using data from The Cancer Genome Atlas (TCGA) and the Epigenome-Wide Association Study (EWAS) databases. Clinical tissue specimens from Peking University First Hospital were then examined to explore the association between SPAG6 expression/methylation and the clinicopathological features of RCC patients. The correlation between SPAG6 expression and promoter methylation was further validated in RCC cell lines. Functional roles of SPAG6 in cell proliferation, invasion, cell cycle regulation, and apoptosis were investigated through in vitro cellular assays and in vivo xenograft models. Finally, transcriptome sequencing was performed to explore the molecular mechanisms by which SPAG6 affects RCC development. RESULTS:...