journal contribution
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 S5. Proteomic analysis by GSEA and GO analysis assay established the differential expression under circ-10720 overexpression. (A) GSEA plots for the gene sets in PLC-PRF-5 cells overexpressed circ-10720 or control vectors. (B) Statistical analysis of the up-regulated biological processes, molecular function and cellular component of PLC-PRF-5 cells after circ-10720 overexpression. (C) Up-regulated genes associated with intracellular transport, invadopodia proteins, TGF-β receptor signaling pathways and so on in circ-10720 overexpressed PLC-PRF-5 cells was analyzed.
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.
