CircRNA_104075 Stimulates YAP-dependent Tumorigenesis Through the Regulation of HNF4a and May Serve As a Diagnostic Marker in Hepatocellular Carcinoma

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2018 Oct 27

PMID 30361504

Citations 127

Authors

Xiao Zhang

Yanfeng Xu

Zijun Qian

Weisheng Zheng

Qi Wu

Yan Chen

Guoqing Zhu

Ya Liu

Zhixuan Bian

Wen Xu

Yue Zhang

Fenyong Sun

Qiuhui Pan

Jiayi Wang

Lutao Du

Yongchun Yu

Affiliations

Soon will be listed here.

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 N-methyladenosine (mA) motif was identified in the 353-357 region of YAP 3'UTR, and this mA 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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