Xu Xuemeng, Peng Qiu, Ren Zongyao, Han Yaqian, Jiang Xianjie, Wu Zhu, Tan Shiming, Yang Wenjuan, Oyang Linda, Luo Xia, Lin Jinguan, Xia Longzheng, Peng Mingjing, Wu Nayiyuan, Tang Yanyan, Tian Hao, Zhou Yujuan, Liao Qianjin
The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Hunan Key Laboratory of Cancer Metabolism, Changsha, Hunan, 410013, P. R. China.
Hunan Engineering Research Center of Tumor organoid Technology and application, Public Service Platform of Tumor organoids Technology, 283 Tongzipo Road, Changsha, Hunan, 410013, P. R. China.
Mol Cancer. 2025 Jan 31;24(1):36. doi: 10.1186/s12943-025-02239-4.
Oral cancer ranks among the most common malignancies within the head and neck region; however, its etiology remains inadequately understood despite substantial research advances in recent years. Many studies highlight the regulatory role of circular RNAs (circRNAs) in human cancers, suggesting their potential as cancer biomarkers. However, their specific mechanisms in oral cancer are not well understood. This study analyzed circRNAs expression in oral cancer, identifying circRNF13 (circbaseID: has_circ_0006801) as having elevated expression in oral cancer cells and tissues. Our study demonstrated that circRNF13 is correlated with increased tumor grade and stage in oral cancer. Results from both in vitro and in vivo experiments indicated that circRNF13 enhances cancer cell proliferation and tumor growth, while concurrently diminishing tumor sensitivity to cisplatin. Mechanistically, circRNF13 interacts with the m6A "reader" protein IGF2BP1, inhibiting its ubiquitin-mediated degradation and promoting its phase separation formation. Subsequently, circRNF13 augments the stability of ITGB1 mRNA via IGF2BP1 in a manner dependent on m6A modification. The m6A modification of ITGB1 mRNA is modulated by the phase separation of IGF2BP1, thereby promoting the malignant progression of oral cancer cells. This evidence positions circRNF13 as a crucial regulatory molecule in the pathogenesis of oral cancer and suggests its potential as a therapeutic target. This discovery enriches our understanding of the mechanistic role of circRNAs.
口腔癌是头颈部最常见的恶性肿瘤之一；然而，尽管近年来研究取得了重大进展，但其病因仍未得到充分了解。许多研究强调了环状RNA（circRNA）在人类癌症中的调控作用，并表明它们具有作为癌症生物标志物的潜力。然而，它们在口腔癌中的具体机制尚不清楚。本研究分析了口腔癌中circRNA的表达，发现circRNF13（circbaseID：has_circ_0006801）在口腔癌细胞和组织中表达升高。我们的研究表明，circRNF13与口腔癌中肿瘤分级和分期的增加相关。体外和体内实验结果均表明，circRNF13增强癌细胞增殖和肿瘤生长，同时降低肿瘤对顺铂的敏感性。机制上，circRNF13与m6A“读取器”蛋白IGF2BP1相互作用，抑制其泛素介导的降解并促进其相分离形成。随后，circRNF13通过IGF2BP1以依赖于m6A修饰的方式增强ITGB1 mRNA的稳定性。ITGB1 mRNA的m6A修饰由IGF2BP1的相分离调节，从而促进口腔癌细胞的恶性进展。这一证据表明circRNF13是口腔癌发病机制中的关键调控分子，并提示其作为治疗靶点的潜力。这一发现丰富了我们对circRNA机制作用的理解。
