Yao Xuelin, Liu Hanyuan, Wang Zhen, Lu Fangting, Chen Wenying, Feng Qing, Miao Yahu, Zhang Jie, Wang Yanlei, Chen Ye, Xue Liping, Liu Yehai, Chen Liang, Zhang Qiu
Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Department of Obstetrics and Gynecology, Core Facility Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Oncogene. 2023 Oct;42(43):3206-3218. doi: 10.1038/s41388-023-02830-3. Epub 2023 Sep 11.
Circular RNAs (circRNAs) play an important role in regulating the development of human cancers through diverse biological functions. However, the exact molecular mechanisms underlying the role of circRNAs in papillary thyroid cancer (PTC) remain largely unknown. Here, we found that hsa_circ_0011385, designated as circular eukaryotic translation initiation factor 3 subunit I (circEIF3I), preferentially localized in the cytoplasm of PTC cells and was more stable than its linear counterpart, EIF3I. Gain- and loss-of-function studies indicated that circEIF3I promoted PTC progression by facilitating cell proliferation, cell cycle, cell migration, and invasion in vitro, as well as PTC cell proliferation in vivo. Mechanistically, circEIF3I interacted with AU-rich element (ARE) RNA-binding factor 1 (AUF1) in the cytoplasm of PTC cells, thus reducing the degradation of Cyclin D1 mRNA and increasing Cyclin D1 protein production, ultimately resulting in PTC progression. Collectively, our results demonstrate the vital role of circEIF3I in PTC progression, supporting its significance as a potential therapeutic target.
环状RNA(circRNAs)通过多种生物学功能在调节人类癌症发展中发挥重要作用。然而,circRNAs在甲状腺乳头状癌(PTC)中作用的具体分子机制仍 largely未知。在此,我们发现hsa_circ_0011385,命名为环状真核翻译起始因子3亚基I(circEIF3I),优先定位于PTC细胞的细胞质中,并且比其线性对应物EIF3I更稳定。功能获得和功能丧失研究表明,circEIF3I通过促进体外细胞增殖、细胞周期、细胞迁移和侵袭以及体内PTC细胞增殖来促进PTC进展。机制上,circEIF在PTC细胞的细胞质中与富含AU元件(ARE)的RNA结合因子1(AUF1)相互作用,从而减少细胞周期蛋白D1 mRNA的降解并增加细胞周期蛋白D1蛋白的产生,最终导致PTC进展。总体而言,我们的结果证明了circEIF3I在PTC进展中的重要作用,支持其作为潜在治疗靶点的意义。