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Abstract
Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA_104075 (circ_104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the −1409 to −1401 region of the circ_104075 promoter to stimulate the expression of circ_104075. Moreover, circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. Interestingly, an N6-methyladenosine (m6A) motif was identified in the 353–357 region of YAP 3′UTR, and this m6A modification was essential for the interaction between miR-582-3p and YAP 3′UTR. Further, the diagnostic performance of circ_104075 was evaluated. The area under the receiver operating characteristic (AUC-ROC) for circ_104075 was 0.973 with a sensitivity of 96.0% and a specificity of 98.3%. Collectively, we determined that circ_104075 was highly expressed in HCC and elucidated its upstream and downstream regulatory mechanisms. circ_104075 additionally has the potential to serve as a new diagnostic biomarker in HCC. Targeting circ_104075 may provide new strategies in HCC diagnosis and therapy.
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1 Department of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China
2 Department of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
3 Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
4 School of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, China
5 Department of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
6 Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
7 Department of Central Laboratory, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China
8 Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China
9 Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China