Profiling and bioinformatic analysis of circular RNA expression regulated by c-Myc

// Qiheng Gou 1, * , Ke Wu 1, * , Jian-Kang Zhou 1 , Yuxin Xie 2 , Lunxu Liu 1 and Yong Peng 1 1 Department of Thoracic Surgery and Lab of Non-Coding RNAs in Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China 2 Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China * These authors contributed equally to this work Correspondence to: Yong Peng, email: yongpeng@scu.edu.cn Lunxu Liu, email: lunxu_liu@aliyun.com Keywords: circular RNA, microRNA, c-Myc, profiling, bioinformatics analysis Received: February 08, 2017 Accepted: March 26, 2017 Published: May 10, 2017 ABSTRACT The c-Myc transcription factor is involved in cell proliferation, cell cycle and apoptosis by activating or repressing transcription of multiple genes. Circular RNAs (circRNAs) are widely expressed non-coding RNAs participating in the regulation of gene expression. Using a high-throughput microarray assay, we showed that Myc regulates the expression of certain circRNAs. A total of 309 up- and 252 down-regulated circRNAs were identified. Among them, randomly selected 8 circRNAs were confirmed by real-time PCR. Subsequently, Myc-binding sites were found to generally exist in the promoter regions of differentially expressed circRNAs. Based on miRNA sponge mechanism, we constructed circRNAs/miRNAs network regulated by Myc, suggesting that circRNAs may widely regulate protein expression through miRNA sponge mechanism. Lastly, we took advantage of Gene Ontology and KEGG analyses to point out that Myc-regulated circRNAs could impact cell proliferation through affecting Ras signaling pathway and pathways in cancer. Our study for the first time demonstrated that Myc transcription factor regulates the expression of circRNAs, adding a novel component of the Myc tumorigenic program and opening a window to investigate the function of certain circRNAs in tumorigenesis.