1. Upregulation of Circular RNA circATRNL1 to Sensitize Oral Squamous Cell Carcinoma to Irradiation
- Author
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Xiliu Zhang, Wei Zhao, Yi He, Binghui Zeng, Chen Yi, Dongsheng Yu, Yiming Li, Guanhui Chen, and Chao Wang
- Subjects
0301 basic medicine ,biology ,RNA ,Article ,03 medical and health sciences ,stomatognathic diseases ,030104 developmental biology ,0302 clinical medicine ,Downregulation and upregulation ,Circular RNA ,Tumor progression ,Apoptosis ,030220 oncology & carcinogenesis ,Drug Discovery ,Gene expression ,Cancer research ,biology.protein ,Molecular Medicine ,PTEN ,Radiosensitivity - Abstract
Accumulating evidence has demonstrated that circular RNAs (circRNAs) play important roles in regulating gene expression involved in tumor development. However, the role of circRNAs in modulating the radiosensitivity of oral squamous cell carcinoma (OSCC) and its potential mechanisms have not been documented. We performed high-throughput RNA sequencing (RNA-seq) to investigate the circRNA expression profile in OSCC patients and discovered that the circATRNL1 expression was significantly downregulated and closely related to tumor progression. The circATRNL1 was structurally validated via Sanger sequencing, RNase R treatment, and specific convergent and divergent primer amplification. Importantly, the expression levels of circATRNL1 decreased after irradiation treatment, and upregulation of circATRNL1 enhanced the radiosensitivity of OSCC through suppressing proliferation and the colony survival fraction, inducing apoptosis and cell-cycle arrest. Moreover, we observed that circATRNL1 could directly bind to microRNA-23a-3p (miR-23a-3p) and relieve inhibition for the target gene PTEN. In addition, the tumor radiosensitivity-promoting effect of circATRNL1 overexpression was blocked by miR-23a-3p in OSCC. Further experiments also showed that PTEN can reverse the inhibitory effect of OSCC radiosensitivity triggered by miR-23a-3p. We concluded that circANTRL1 may function as the sponge of miR-23a-3p to promote PTEN expression and eventually contributes to OSCC radiosensitivity enhancement. This study indicates that circANTRL1 may be a novel therapeutic target to improve the efficiency of radiotherapy in OSCC.
- Published
- 2020