Unraveling the miR-144-3p/PUMA pathway: a novel regulator of FDX1-mediated cuproptosis in colorectal cancer

作者：Guiyun Jia, Jiehan Li, Meimei Jiang, Nannan Liu, Ning Ding, Xinxiu Jiang, Ge Zhang, Xiaoxiao Tan, Ying Kang, Lingling Zhang, Feng Wang, Yingjie Zhang · 发表于：Cellular Oncology · 年份：2025 · DOI：10.1007/s13402-025-01093-2 · 被引用次数：5 · 研究领域：MicroRNA in disease regulation、Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research

PURPOSE: Cuproptosis represents a novel form of cell death, predominantly driven by excessive intracellular accumulation of Cu+. The mechanisms underlying cuproptosis in colorectal cancer (CRC) remain unknown. This study aims to investigate the underlying mechanisms in CRC, offering a novel therapeutic strategy for its treatment. METHODS: Transcriptomic datasets from The Cancer Genome Atlas (TCGA) databases were analyzed using R-software (v4.3.1) to quantify miR-144-3p expression in CRC. In vitro, CCK-8, EdU, colony formation assays, and Transwell assays were used to assess the proliferative capacity, migratory potential, and invasive properties of CRC under miR-144-3p modulation. Western blotting (WB) further linked miR-144-3p expression to modulation of cuproptosis-related pathways. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were performed to validate miR-144-3p binding to the 3′-UTR of PUMA mRNA. Co-IP and Immunofluorescence (IF) assays confirmed PUMA-FDX1 binding. DLAT oligomerization was analyzed by WB and IF experiments. The ubiquitination level of FDX1 was detected via Co-IP. In vivo, tumor xenograft experiments using HCT116OE − miR−144−3p and HCT116sh − miR−144−3p cell lines were performed in nude mice. RESULTS: In this study, miR-144-3p, a recently identified microRNA, was found to be aberrantly upregulated in CRC. It significantly promoted the proliferation, migration, and invasion of CRC both in vitro and in vivo. Mechanistically, miR-144-3p ...