Circular RNA Circ0021205 Promotes Cholangiocarcinoma Progression Through MiR-204-5p/RAB22A Axis.

Jianfei Tu,Jianfei Tu,Jiansong Ji,Zhongwei Zhao,Zhongwei Zhao,Yang Yang,Yang Yang,Chunli Kong,Chunli Kong,Xiaojie Lu,Xiaojie Lu,Xiaojie Lu,Liyun Zheng,Shiji Fang,Shiji Fang,Chenying Lu,Weiqian Chen,Weiqian Chen,Dengke Zhang,Dengke Zhang,Jiansong Ji,Rongfang Qiu,Rongfang Qiu

doi:10.3389/fcell.2021.653207

Abstract

Cholangiocarcinomas (CCA) are biliary tract tumors that are often challenging to diagnosis and treatment. Accumulated evidence reveals that circular RNAs (circRNAs) are involved in multiple cancer progression. However, the function of circRNAs in cholangiocarcinoma remains largely unclear. In this study, we found that circ_0021205 expression was up-regulated in CCA and positively correlated with tumor size and TNM stage. To further explore the role of circ_0021205 in CCA, cell functional assays were performed. The results showed that circ_0021205 promoted the proliferation, migration, and invasion of CCA cells. In vivo experiments showed that circ_0021205 inhibition reduced tumorigenesis in mice. In addition, mechanisms investigation demonstrated that circ_0021205 exerts its oncogenic function by sponging miR-204-5p to regulate the expression of RAB22A. Overall, this study revealed that circ_0021205 might serve as a potential diagnostic biomarker or therapeutic target for CCA.

Highlights

Cholangiocarcinoma (CCA) is a highly malignant tumor found in the epithelial cells lining the bile duct, which is categorized according to anatomical location as intrahepatic, perihilar, and distal cholangiocarcinoma (Cunningham et al, 2007; Rizvi et al, 2018)
HuCCT1 and KMBC cell lines were selected for further study for the relative high or low expression level of circ_0021205 among 6 CCA cell lines
In recent years, emerging evidence illustrates that many circRNAs function as tumor suppressors or promoters in several cancers, such as hepatocellular carcinoma, lung cancer, gastric cancer, and cholangiocarcinoma (Yang et al, 2019)

Summary

Introduction

Cholangiocarcinoma (CCA) is a highly malignant tumor found in the epithelial cells lining the bile duct, which is categorized according to anatomical location as intrahepatic, perihilar, and distal cholangiocarcinoma (Cunningham et al, 2007; Rizvi et al, 2018). In the past 30–40 years, the global incidence of cholangiocarcinoma has risen to 18% of all liver cancers (Erichsen et al, 2011). The effective treatments of cholangiocarcinoma are surgical resection, liver transplantation, and drug therapy (Kinoshita et al, 2008; Wechagama et al, 2012). The therapeutic effects of radiotherapy and chemotherapy are relatively poor. The only effective treatment method is early surgical resection of cholangiocarcinoma (Fidelman et al, 2011; Patop et al, 2019).

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