Erianin Abrogates Cancerous Vasculogenic Mimicry Through Targeting m 5 C Methylase NSUN2 in Uveal Melanoma

作者：Sipeng Zuo, S.‐I. HO, Lin Li, Jieling Tang, Zhimin Tang, Fanglin He, Yan Liu, Jiaying Zhang, Fuxiang Ye, Xianqun Fan, Peiwei Chai, Linna Lu · 发表于：Investigative Ophthalmology & Visual Science · 年份：2025 · DOI：10.1167/iovs.66.15.47 · 被引用次数：1 · 研究领域：RNA modifications and cancer、Metalloenzymes and iron-sulfur proteins、Protein Tyrosine Phosphatases

Purpose: The regulatory role of N5-methylcytosine (m5C) RNA modification is of vital importance for the metabolism of RNA. As a natural product isolated from Dendrobium chrysotoxum Lindl., erianin shows promising therapeutic efficacy in cancer therapy. Herein, we determined that erianin serves as a naturally occurring NOP2/Sun RNA methyltransferase 2 (NSUN2) inhibitor in malignant vascular formation in uveal melanoma. Methods: Natural product library screening was conducted to explore the effects of natural product monomers on uveal melanoma cells. An intraocular xenografts model was established to examine the effect of erianin. Immunoprecipitation and mass spectrometry (IP-MS) and molecular docking analyses were used to identify NSUN2 as the target of erianin. m5C-methylated RNA immunoprecipitation sequencing (MeRIP-seq) and m5C-MeRIP quantitative PCR (MeRIP-qPCR) analyses were conducted to identify the downstream target of NSUN2. Tube formation assay and CD31/periodic acid-Schiff (PAS) double staining were performed to detect vasculogenic mimicry (VM) capacities. Results: Here, employing Cell Counting Kit-8 (CCK-8), colony-formation, and Transwell assays, we demonstrated that erianin markedly restrains uveal melanoma (UM) proliferation and invasion in vitro. Biotin-linked affinity enrichment coupled to mass spectrometry identified the m5C methyltransferase NSUN2 as a direct molecular target of erianin. Functionally, erianin disrupts NSUN2-mediated m5C modification and there...