Li Yan, Meng Fandong, Sui Chengguang, Wang Yang, Cheng Dali
Department of Biotherapy, Cancer Research Institute, The First Hospital of China Medical University, 110001, Shenyang, Liaoning, China.
Department of Gynaecology and Obstetrics, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, 110000, Shenyang, Liaoning, China.
J Cell Commun Signal. 2023 Sep;17(3):627-638. doi: 10.1007/s12079-022-00696-w. Epub 2022 Nov 10.
Circular RNAs (CircRNAs) are key regulators in the development and progression of human cancers. However, the biological roles and mechanisms of circRNAs in gastric cancer (GC) remain largely unknown. Analyzing circRNA microarray dataset (GSE102686) and clinical specimens, a novel circRNA termed hsa_circ_0001627, was identified and it was highly expressed in CC cancerous tissues and cells, and was associated with poor clinical outcomes. Functionally, hsa_circ_0001627 silencing impaired the malignant progression of CC cells and the growth of CC xenografts in nude mice. Mechanistically, hsa_circ_0001627 acted as a miR-1225-5p sponge, thus indirectly regulating FNDC3B and leading to the activation of PI3K/mTOR signaling pathway. Collectively, the present study indicates that hsa_circ_0001627 regulates miR-1225-5p/FNDC3B/PI3K/mTOR axis and functions as an oncogene in CC progression, suggesting the potential therapeutic use of hsa_circ_0001627 in CC treatment.
环状RNA(CircRNAs)是人类癌症发生和发展的关键调节因子。然而,circRNAs在胃癌(GC)中的生物学作用和机制仍 largely未知。通过分析circRNA微阵列数据集(GSE102686)和临床标本,鉴定出一种名为hsa_circ_0001627的新型circRNA,它在CC癌组织和细胞中高表达,并与不良临床预后相关。在功能上,hsa_circ_0001627沉默会损害CC细胞的恶性进展以及裸鼠中CC异种移植瘤的生长。机制上,hsa_circ_0001627作为miR-1225-5p的海绵,从而间接调节FNDC3B并导致PI3K/mTOR信号通路的激活。总体而言,本研究表明hsa_circ_0001627调节miR-1225-5p/FNDC3B/PI3K/mTOR轴,并在CC进展中作为癌基因发挥作用,提示hsa_circ_0001627在CC治疗中的潜在治疗用途。