Sun Xinyu, Zhang Yanshu, Wang Huirong, Pu Xi, Yuan Xiao, Liang Yuntong, Liu Hao, Wang Xu, Lu Hanqiang
Department of Otorhinolaryngology, Affiliated Hospital of Jiangsu University, 212000, Zhenjiang, Jiangsu Province, China.
Department of Radiation Oncology, Cancer Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, 212000, Zhenjiang, Jiangsu Province, China.
Cancer Gene Ther. 2025 Jan;32(1):122-135. doi: 10.1038/s41417-024-00863-8. Epub 2024 Dec 9.
Insulin-like growth factor binding protein 2 (IGF2BP2) fulfills a key role in the development of head and neck squamous cell carcinoma (HNSCC). Radiotherapy is an effective method to treat HNSCC; however, radiation resistance is the main reason for treatment failure. At present, the carcinogenic role of IGF2BP2 in terms of the proliferation of HNSCC and the radioresistance of its therapy remain poorly understood. In the present study, patients with HNSCC with higher IGF2BP2 expression levels were associated with shorter survival times. IGF2BP2 is significantly upregulated in HNSCC cells compared with irradiated cell. Based on functional studies, IGF2BP2 was found to promote HNSCC cell proliferation and tolerance to radiotherapy both in vitro and in vivo. In terms of the underlying mechanism, RIMS binding protein 2 (RIMBP2) was found to be highly expressed in HNSCC and to promote the proliferation of HNSCC and radiotherapy resistance. RIMBP2 was shown to be a direct target of IGF2BP2, activating endoplasmic reticulum stress in HNSCC. In addition, it has been demonstrated that IGF2BP2, as m6A reader, is able to promote RIMBP2 stability via binding to m6A sites in the RIMBP2-coding sequence region. Therefore, the present study has unveiled a potential mechanism via which IGF2BP2 promotes HNSCC development and radiotherapy resistance; moreover, from a therapeutic perspective, IGF2BP2 may serve as a potential therapeutic target and a valuable prognostic biomarker for patients with HNSCC who have developed tolerance towards radiotherapy.
胰岛素样生长因子结合蛋白2（IGF2BP2）在头颈部鳞状细胞癌（HNSCC）的发展中起关键作用。放射治疗是治疗HNSCC的有效方法；然而，放射抗性是治疗失败的主要原因。目前，IGF2BP2在HNSCC增殖及其治疗的放射抗性方面的致癌作用仍知之甚少。在本研究中，IGF2BP2表达水平较高的HNSCC患者生存时间较短。与受照射细胞相比，IGF2BP2在HNSCC细胞中显著上调。基于功能研究，发现IGF2BP2在体外和体内均能促进HNSCC细胞增殖和对放疗的耐受性。就潜在机制而言，发现RIMS结合蛋白2（RIMBP2）在HNSCC中高表达，并促进HNSCC的增殖和放疗抗性。RIMBP2被证明是IGF2BP2的直接靶点，可激活HNSCC中的内质网应激。此外，已证明IGF2BP2作为m6A阅读器，能够通过与RIMBP2编码序列区域中的m6A位点结合来促进RIMBP2的稳定性。因此，本研究揭示了IGF2BP2促进HNSCC发展和放疗抗性的潜在机制；此外，从治疗角度来看，IGF2BP2可能作为对放疗产生耐受性的HNSCC患者的潜在治疗靶点和有价值的预后生物标志物。
