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.

Details

Title
circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma
Author
Zhang, Xiao 1 ; Xu, Yanfeng 2 ; Qian, Zijun 3 ; Zheng, Weisheng 4 ; Wu, Qi 1 ; Chen, Yan 1 ; Zhu, Guoqing 1 ; Liu, Ya 1 ; Bian, Zhixuan 5 ; Xu, Wen 6 ; Zhang, Yue 7 ; Sun, Fenyong 1 ; Pan, Qiuhui 5 ; Wang, Jiayi 1 ; Du, Lutao 8 ; Yu, Yongchun 9 

 Department of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China 
 Department of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China 
 Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China 
 School of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, China 
 Department of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China 
 Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China 
 Department of Central Laboratory, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China 
 Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China 
 Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 
Pages
1-14
Publication year
2018
Publication date
Oct 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2125272731
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.