Affiliation:
1. Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Key Laboratory of Liver Transplantation Chinese Academy of Medical Sciences NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University) Nanjing Jiangsu 210029 China
2. School of Medicine Southeast University Nanjing Jiangsu 210009 China
3. The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi People's Hospital Wuxi Medical Center Nanjing Medical University Wuxi Jiangsu 214023 China
Abstract
AbstractIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients’ prognosis. Moreover, circUGP2 overexpression suppresses tumor progression in vitro and in vivo. Mechanistically, circUGP2 functions as a transcriptional co‐activator of PURB over the expression of ADGRB1. It can also upregulate ADGRB1 expression by sponging miR‐3191‐5p. As a result, ADGRB1 prevents MDM2‐mediated p53 polyubiquitination and thereby activates p53 signaling to inhibit ICC progression. Based on these findings, circUGP2 plasmid is encapsulated into a lipid nanoparticle (LNP) system, which has successfully targeted tumor site and shows superior anti‐tumor effects. In summary, the present study has identified the role of circUGP2 as a tumor suppressor in ICC through regulating ADGRB1/p53 axis, and the application of LNP provides a promising translational strategy for ICC treatment.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province