The Mechanism and Clinical Significance of Circular RNAs in Hepatocellular Carcinoma

Ziyue Huang,Wangming Chen,Shuqiang Liu,Risheng He,Haoming Xia,Pengcheng Kang,Judy Wai Ping Yam,Zhongrui Wang,Zhilei Su,Xudong Zhao,Yi Xu,Wenguang Shi,Yunfu Cui

doi:10.3389/fonc.2021.714665

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. In view of the lack of early obvious clinical symptoms and related early diagnostic biomarkers with high specificity and sensitivity, most HCC patients are already at the advanced stages at the time of diagnosis, and most of them are accompanied by distant metastasis. Furthermore, the unsatisfactory effect of the follow-up palliative care contributes to the poor overall survival of HCC patients. Therefore, it is urgent to identify effective early diagnosis and prognostic biomarkers and to explore novel therapeutic approaches to improve the prognosis of HCC patients. Circular RNA (CircRNA), a class of plentiful, stable, and highly conserved ncRNA subgroup with the covalent closed loop, is dysregulated in HCC. Increasingly, emerging evidence have confirmed that dysregulated circRNAs can regulate gene expression at the transcriptional or post-transcriptional level, mediating various malignant biological behaviors of HCC cells, including proliferation, invasion, metastasis, immune escape, stemness, and drug resistance, etc.; meanwhile, they are regarded as potential biomarkers for early diagnosis and prognostic evaluation of HCC. This article reviews the research progress of circRNAs in HCC, expounding the potential molecular mechanisms of dysregulated circRNAs in the carcinogenesis and development of HCC, and discusses those application prospects in the diagnosis and prognosis of HCC.

Highlights

Hepatocellular carcinoma is the sixth most common hepatic malignancy and causes severe burden of mortality, making it rank as the third leading cause of cancer-associated deaths worldwide, with approximately 906,000 new cases and 830,000 deaths [1, 2]
Emerging evidence reveals that the dysregulated circRNA expression in Hepatocellular carcinoma (HCC) clinical specimens was closely related to the clinicopathological characteristics of HCC patients and can act as a miRNA sponge, interact with RNA binding protein (RBP) or a transcriptional regulator, and participate in the regulation of the HCC cells tumorigenesis, proliferation and anti-apoptosis, invasion and metastasis, epithelial-mesenchymal transition (EMT), immune escape, drug resistance, metabolic reprogramming, and other biological processes
Targeting of circRNA in HCC patients may reverse the progress of HCC, so as to develop new therapeutic strategies for HCC

Summary

Introduction

Hepatocellular carcinoma is the sixth most common hepatic malignancy and causes severe burden of mortality, making it rank as the third leading cause of cancer-associated deaths worldwide, with approximately 906,000 new cases and 830,000 deaths [1, 2]. Hsa_circRNA 103809 directly binds to miR-377-3p and negatively regulates its expression, releasing the inhibition of fibroblast growth factor receptor 1 (FGFR1), and promotes the proliferation, metastasis, and cell cycle progression of HCC cells [51].

Results

Conclusion