Circular RNA circARPP21 Acts as a Sponge of miR-543 to Suppress Hepatocellular Carcinoma by Regulating LIFR

Yichao Gu; Fan Wu; Hao Wang; Jiang Chang; Yirui Wang; Xiangcheng Li

doi:10.2147/OTT.S283026

Circular RNA circARPP21 Acts as a Sponge of miR-543 to Suppress Hepatocellular Carcinoma by Regulating LIFR

Onco Targets Ther. 2021 Feb 5:14:879-890. doi: 10.2147/OTT.S283026. eCollection 2021.

Authors

Yichao Gu^{1

2}, Fan Wu³, Hao Wang^{1

2}, Jiang Chang^{1

2}, Yirui Wang^{1

2}, Xiangcheng Li^{1

2}

Affiliations

¹ Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People's Republic of China.
² Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, People's Republic of China.
³ Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Abstract

Background: A large body of evidence has shown that circular RNAs (circRNAs) play a significant role in the progression of some malignant cancers, including hepatocellular carcinoma (HCC). However, the complex mechanism of circRNAs in hepatocellular carcinoma has not been clarified.

Methods: We identified circRNAs by microarray analysis and quantitative real-time polymerase chain reaction (RT-qPCR). We also carried out bioinformatics analysis, luciferase reporter assays, and RNA pull-down assays to define the relationship between microRNA (miR)-543 and circARPP21. Through silencing and overexpression of circARPP21, we investigated the effects of circARPP21 on proliferation, migration, and invasion abilities of HCC cells in vitro and in vivo.

Results: In this study, we found that a novel circRNA, circARPP21 (hsa_circ_0123629), exerts a strong effect on HCC progression. Reduced expression of circARPP21 in HCC patients is correlated with larger tumor size, higher tug-lymph node metastasis (TNM) stage, and poor prognosis as indicated by elevated levels of alpha-fetoprotein (AFP). Conversely, higher expression of circARPP21 can increase leukemia inhibitory factor receptor (LIFR) expression by sponging miR-543. Finally, overexpression of miR-543 can reverse the anti-proliferation and anti-metastasis effects of circARPP21.

Conclusion: The circARPP21/miR-543/LIFR axis suppresses the proliferation, invasion, and migration of hepatocellular carcinoma cells. In addition, circARPP21 can serve as a biomarker in HCC, thus offering a potential new approach to HCC therapy.

Keywords: LIFR; circARPP21; hepatocellular carcinoma; miR-543.