circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1
circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1
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circTP63 作为 ceRNA 通过上调 FOXM1 促进肺鳞状细胞癌进展
DOI：
10.1038/s41467-019-11162-4
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发表时间：
2019-07-19
影响因子：
16.6
通讯作者：
Qin, Wenxin
中科院分区：
文献类型：
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作者：
Cheng, Zhuoan;Yu, Chengtao;Qin, Wenxin
环状RNA（circRNA）被鉴定为多种癌症中的重要调节因子。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。在此，我们探讨了5对LUSC样本中circRNA和mRNA的表达谱。通过分析差异表达的circRNA和失调的mRNA的共表达网络，我们确定了细胞周期相关的circRNA，circTP 63，在LUSC组织中上调，并且其上调与LUSC患者中更大的肿瘤大小和更高的TNM分期相关。升高的circTP 63在体外和体内均促进细胞增殖。在机制上，circTP 63与FOXM 1共享miRNA响应元件。circTP 63竞争性结合miR-873- 3 p并阻止miR-873- 3 p降低FOXM 1的水平，FOXM 1上调CENPA和CENPB，最终促进细胞周期进程。
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.