2025/12/22 by Lu Zhang, Jingyi Xiang, Yali Feng +6 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Cancer-related gene regulation #Epigenetics and DNA Methylation #Phosphodiesterase function and regulation
paper · pdf · doi:10.1186/s43556-025-00378-0
openalex created_date 2025/12/22 · openalex publication_date 2025/12/22 · openalex updated_date 2026/07/23
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, underscoring the need for deeper insights into its molecular mechanisms. The SRY-box transcription factor 9 (SOX9) is a well-characterized oncoprotein critical for the pathogenesis and progression of multiple cancers, including NSCLC. However, the post-translational mechanisms governing SOX9 stability, particularly those mediated by arginine methyltransferases, are poorly defined. In this study, we identify protein arginine methyltransferase 7 (PRMT7) as a novel regulator of SOX9. We demonstrate that PRMT7 directly interacts with SOX9 and enhances its stability in a methyltransferase-dependent manner. Mechanistic investigations reveal that PRMT7 catalyzes mono-methylation of SOX9 at the arginine 160 (R160) residue, which in turn antagonizes SOX9 ubiquitination and subsequent proteasomal degradation mediated by the E3 ligases F-Box and WD repeat domain containing 7 (FBXW7) and kelch like ECH associated protein 1 (KEAP1). Functional assays revealed that PRMT7 promotes NSCLC cell proliferation in vitro and tumorigenesis in vivo in a SOX9-dependent manner. Consistent with these findings, clinical analysis revealed significant co-upregulation of both PRMT7 and SOX9 in NSCLC specimens relative to adjacent normal tissues, with elevated levels of either protein correlating with diminished patient survival. Collectively, our findings establish PRMT7 as a key regulator of SOX9 stability and function, thereby highlighting the PRMT7-SOX9 axis as a promising therapeutic target in NSCLC.