Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells.

Jinsheng Wu,Yuting Liu,Yang Su,Chuanrong Zhu,Shaochuang Wang,Lei Liu

doi:10.3389/fcell.2020.585565

Abstract

Accumulating evidence shows that exosomal circRNAs reflect the physiological status of donor cells, and various cell reactions are induced after exosomal circRNAs are captured by recipient cells. In this study, qRT-PCR was performed to detect circ-0004277 expression in hepatocellular carcinoma (HCC) cell lines, tissues, and plasma exosomes. The effects of circ-0004277 on the proliferation and migration of HCC cells were assessed by cell counting, 5-ethynyl-2′-deoxyuridine assays, Transwell migration assays, and tumor formation in nude mice. We found that circ-0004277 was significantly upregulated in HCC cells, tissues, and plasma exosomes compared to that in normal controls. Overexpression of circ-0004277 enhanced the proliferation, migration, and epithelial-mesenchymal transition (EMT) of HCC cells in vivo and in vitro. Furthermore, exosomes from HCC cells enhanced circ-0004277 expression in surrounding normal cells and stimulated EMT progression. ZO-1, a tight junction adapter protein, was downregulated in HCC tissues. In conclusion, our findings suggest that circ-0004277 promotes the malignant phenotype of HCC cells via inhibition of ZO-1 and promotion of EMT progression. In addition, exosomal circ-0004277 from HCC cells stimulates EMT of peripheral cells through cellular communication to further promote the invasion of HCC into normal surrounding tissues.

Highlights

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer (Kim et al, 2017) and the second most common cause of cancer-related deaths
The results showed that only circ-0004277 was stably increased in the six hepatocellular carcinoma (HCC) cell lines compared to that in HL-7702 cells, indicating that circ-0004277 may be involved in the occurrence of HCC (Figure 1A)
CircRNA is closely associated with the occurrence of HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer (Kim et al, 2017) and the second most common cause of cancer-related deaths. It is the sixth most prevalent cancer worldwide, with poor prognosis and high malignancy (Bosetti et al, 2009; Forner et al, 2012; Niendorf et al, 2015). Further studies on the pathogenesis of HCC are important. Many studies have demonstrated that circRNAs are closely associated with HCC. A study by Han et al has shown that circular RNA circMTO1 serves as a sponge of microRNA-9 to inhibit the progression of hepatocellular carcinoma (Han et al, 2017). It is important to explore the function of circRNAs in the occurrence and progression of HCC

Methods

Results

Conclusion