Wang Biao, Zhang Nianjie, Dai Lin, Zhang Yuanwei, Yin Shuo, Yang Xuefeng
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, 563006, Guizhou, People's Republic of China.
Discov Oncol. 2025 Jan 20;16(1):63. doi: 10.1007/s12672-025-01805-y.
Nonylphenol (NP) is a common environmental contaminant and endocrine disruptor. Our previous research demonstrated that NP could promote the proliferation and epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells; however, the specific mechanism remains unclear. miRNA sequencing revealed that NP upregulated the expression levels of microRNA(miR)-151a-3p in CRC. Analysis of The Cancer Genome Atlas (TCGA) data revealed increased expression levels of miR-151a-3p in CRC tissues. The present experiments showed that NP could activate the WNT/β-catenin signaling pathway, and promoted the migration and invasion of CRC cells by increasing the expression levels of miR-151a-3p. Through bioinformatics analysis and dual-luciferase reporter assays, Fyn-related kinase (FRK) was identified as a target gene of miR-151a-3p. Knockdown of FRK promoted NP-induced EMT in CRC cells and activated the WNT/β-catenin signaling pathway, while overexpression had the opposite effect. In summary, the present study demonstrated that NP could inhibit FRK expression via miR-151a-3p, activate the WNT/β-catenin signaling pathway, and promote EMT in CRC cells.
壬基酚（NP）是一种常见的环境污染物和内分泌干扰物。我们之前的研究表明，NP可促进结直肠癌（CRC）细胞的增殖和上皮-间质转化（EMT）；然而，具体机制仍不清楚。miRNA测序显示，NP上调了CRC中微小RNA（miR）-151a-3p的表达水平。对癌症基因组图谱（TCGA）数据的分析显示，CRC组织中miR-151a-3p的表达水平升高。本实验表明，NP可激活WNT/β-连环蛋白信号通路，并通过增加miR-151a-3p的表达水平促进CRC细胞的迁移和侵袭。通过生物信息学分析和双荧光素酶报告基因检测，Fyn相关激酶（FRK）被确定为miR-151a-3p的靶基因。敲低FRK可促进NP诱导的CRC细胞EMT并激活WNT/β-连环蛋白信号通路，而过表达则产生相反的效果。总之，本研究表明，NP可通过miR-151a-3p抑制FRK表达，激活WNT/β-连环蛋白信号通路，并促进CRC细胞的EMT。
