Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, China.
Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, 230601, China.
Biochem Genet. 2024 Oct;62(5):3977-3995. doi: 10.1007/s10528-023-10630-3. Epub 2024 Jan 23.
Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.
甲状腺乳头状癌(PTC)是最常见的甲状腺癌类型,其发病率在全球范围内呈上升趋势。PTC 进展的分子机制仍不清楚,这阻碍了有效治疗方法的发展。本研究聚焦于 hsa_circ_0008016(circFGFR1),一种在 PTC 细胞中显著上调的环状 RNA。沉默 circFGFR1 抑制了 PTC 细胞的增殖并增加了细胞凋亡,提示其在 PTC 进展中的作用。RNA 结合蛋白 FUS 被鉴定为 circFGFR1 形成的促进剂。虽然 circFGFR1 不影响 FGFR1 mRNA 的翻译,但它抑制 FGFR1 蛋白的泛素化和降解,延长其半衰期。circFGFR1 还与蛋白 CBL 相互作用,抑制 CBL 介导的 FGFR1 蛋白泛素化。挽救实验证实 circFGFR1 通过介导 FGFR1 促进 PTC 细胞的生长。本研究强调了 circFGFR1 作为治疗靶点的潜力,为 PTC 的分子机制提供了新的见解,并为新的治疗策略铺平了道路。