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Figure S3 from Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

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posted on 2023-03-31, 01:45 authored by Jing Meng, Shuang Chen, Jing-Xia Han, Baoxin Qian, Xiao-Rui Wang, Wei-Long Zhong, Yuan Qin, Heng Zhang, Wan-Feng Gao, Yue-Yang Lei, Wei Yang, Lan Yang, Chao Zhang, Hui-Juan Liu, Yan-Rong Liu, Hong-Gang Zhou, Tao Sun, Cheng Yang

Figure S3. The bioinformatic prediction of circ-10720-miRNAs, miRNA-Vimentin binding site. (A)The bioinformatic prediction (circInteractome datebase) of the putative binding sites of circ-10720 with miRNAs and mutated each miRNA target site of the circ-10720 sequence. (B)The bioinformatic prediction (microRNA datebase) of the putative binding sites of Vimentin 3'-UTR with miR-1246, miR-578, miR-490-5p and mutated miRNA sequence. (C) Expression level of miR-1246, miR-578, and miR-490-5p in human normal tissues and hepatocellular carcinoma tissues.

Funding

National Natural Science Foundation of China

Natural Science Foundation of Tianjin City

National Science and Technology Major Project

Tianjin Science and Technology Project

History

ARTICLE ABSTRACT

Twist is a critical epithelial–mesenchymal transition (EMT)–inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1 in vitro and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.Significance: A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg. Cancer Res; 78(15); 4150–62. ©2018 AACR.