State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Biomedical Engineering, 200032, Shanghai, China.
Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, China.
Nat Commun. 2019 Jul 19;10(1):3200. doi: 10.1038/s41467-019-11162-4.
Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the role of circRNA in lung squamous cell carcinoma (LUSC) remains largely unknown. Herein, we explore the expression profiles of circRNA and mRNA in 5 paired samples of LUSC. By analyzing the co-expression network of differentially expressed circRNAs and dysregulated mRNAs, we identify that a cell cycle-related circRNA, circTP63, is upregulated in LUSC tissues and its upregulation is correlated with larger tumor size and higher TNM stage in LUSC patients. Elevated circTP63 promotes cell proliferation both in vitro and in vivo. Mechanistically, circTP63 shares miRNA response elements with FOXM1. circTP63 competitively binds to miR-873-3p and prevents miR-873-3p to decrease the level of FOXM1, which upregulates CENPA and CENPB, and finally facilitates cell cycle progression.
环状 RNA（circRNAs）被鉴定为多种癌症中的重要调控因子。然而，circRNA 在肺鳞状细胞癌（LUSC）中的作用在很大程度上仍然未知。本研究通过分析差异表达的 circRNA 和失调的 mRNA 的共表达网络，发现一个与细胞周期相关的 circRNA，circTP63，在 LUSC 组织中上调，其上调与 LUSC 患者更大的肿瘤大小和更高的 TNM 分期相关。circTP63 在体外和体内均促进细胞增殖。机制上，circTP63 与 FOXM1 共享 miRNA 反应元件。circTP63 竞争性结合 miR-873-3p，防止 miR-873-3p 降低 FOXM1 的水平，上调 CENPA 和 CENPB，最终促进细胞周期进程。
