Abstract
ABSTRACTAccumulating evidence suggests that circular RNAs (circRNAs) play important roles in various physiological and pathological processes. In the present study, we explored the role of circRNA PVT1 in hepatocellular carcinoma (HCC). qRT-PCR was performed to detect the relative expression of circPVT1 in HCC tissues and cell lines. The oncogenic roles of circPVT1 in HCC were evaluated by cell counting kit-8 (CCK-8) assay, ethynyl deoxyuridine (EdU) incorporation assays, transwell assays, flow cytometry and in vivo xenograft growth. Furthermore, bioinformatics, luciferase reporter assays and rescue experiments were conducted to determine the underlying mechanism of circPVT1 in HCC. Enhanced circPVT1 expression was detected in HCC tissues, which was closely associated with poor prognosis of patients with HCC. Knockdown of circPVT1 decreased the proliferation and migration ability of HCC cell lines in vitro. Conversely, upregulation of circPVT1 improved the growth and migration in HCC cells. Mechanistically, we found that circPVT1 could bind directly to miR-203 and contributed to the initiation and progression of HCC by regulating miR-203/homebox D3 (HOXD3) pathway. In conclusion, our study reveals that circPVT1 participates in the progression of HCC through the miR-203/homeobox D3 (HOXD3) pathway and might represent a potential therapeutic target for HCC treatment.
Highlights
Liver cancer is among the most common cancers worldwide, leading to approximately 600,000 deaths each year (Baffy et al, 2012)
We discovered that circPVT1 participated in the progression of Hepatocellular carcinoma (HCC) through regulating miR-203/homeobox D3 (HOXD3) pathway
The data revealed that circPVT1 was significantly upregulated in HCC tissues compared with the paired non-tumor tissues (Fig. 1A)
Summary
Liver cancer is among the most common cancers worldwide, leading to approximately 600,000 deaths each year (Baffy et al, 2012). Hepatocellular carcinoma (HCC) accounts for more than half of all liver cancer and is closely related with chronic hepatitis B virus (HBV) infection (Lee et al, 2019). Recent advances have been made in surgical treatment, effective therapy for HCC is still limited and the overall survival of HCC patients remains poor. Circular RNAs (circRNAs) are a type of noncoding RNAs (ncRNAs) that are generated by circularization of introns or exons (Chen, 2016). Recent progress in next-generation deep sequencing has reshaped our perspective of circRNAs (Li et al, 2018b). The expression level of circPVRL3 was decreased in gastric cancer and was associated with unfavorable overall survival (Sun et al, 2018). The exact role of circRNAs in HCC remains elusive
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