Pan Ke-Fan, Chou Han-Lin, Wang Wei-Li, Chen Bo-Rong, Hsiao Michael, Hua Kuo-Tai, Wu Ming-Hsun
Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Br J Cancer. 2025 Aug 23. doi: 10.1038/s41416-025-03142-x.
K-homology-type splicing regulatory protein (KSRP) is an RNA-binding protein involved in mRNA decay and translational repression through recognition of adenine-uracil-rich elements. Although KSRP regulates approximately 16% of transcript expression, its role in cancer remains poorly defined.
KSRP expression was analysed using qPCR, Western blot, and immunohistochemistry. Its functional role in follicular thyroid cancer (FTC) was examined through in vitro and in vivo assays. Luciferase reporter and rescue experiments were performed to elucidate the underlying molecular mechanisms.
KSRP was significantly upregulated in FTC tissues and metastatic cell lines. Functional studies demonstrated that KSRP enhances the invasiveness and stemness of FTC cells. Mechanistically, KSRP promotes nuclear accumulation and transcriptional activity of β-catenin by downregulating the Wnt inhibitors DACT2 and SFRP2.
This study identifies KSRP as an oncogenic factor in FTC that activates Wnt/β-catenin signalling, suggesting its potential as a therapeutic target for FTC patients.
K-同源性剪接调节蛋白（KSRP）是一种RNA结合蛋白，通过识别富含腺嘌呤-尿嘧啶的元件参与mRNA降解和翻译抑制。尽管KSRP调节约16%的转录本表达，但其在癌症中的作用仍不清楚。
采用qPCR、蛋白质免疫印迹和免疫组织化学分析KSRP表达。通过体外和体内实验研究其在滤泡性甲状腺癌（FTC）中的功能作用。进行荧光素酶报告基因和拯救实验以阐明潜在的分子机制。
KSRP在FTC组织和转移细胞系中显著上调。功能研究表明，KSRP增强FTC细胞的侵袭性和干性。机制上，KSRP通过下调Wnt抑制剂DACT2和SFRP2促进β-连环蛋白的核积累和转录活性。
本研究确定KSRP为FTC中的致癌因子，可激活Wnt/β-连环蛋白信号通路，提示其作为FTC患者治疗靶点的潜力。
