Circular RNA circ SET domain containing 2 (circSETD2) inhibits hepatocellular carcinoma cell proliferation and invasion in vivo and in vitro

Liver cancer is a common malignant tumor with high incidence and mortality rates. However, a reliable prognostic signature has not yet been confirmed. Circular RNAs (circRNAs) play a role in the development and prognosis of numerous malignancies as well as liver cancer. Therefore, identifying abnormally expressed circRNAs in liver cancer tissue is essential for early diagnosis and treatment. This study found that circular RNA circ SET domain containing 2 (circSETD2) is abnormally expressed in liver cancer tissues, but the role and molecular mechanismsin the occurrence and development of liver cancer are still unclear. The expression level of circSETD2 was evaluated through Quantitative Real-time Polymerase chain reaction (qRT-PCR) in cancerous liver tissues (30 cases), liver cancer cell lines and para-cancerous tissues. Knockdown and overexpression circSETD2 lentiviral vector was constructed and applied to transfect hepatoma cells. Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and Transwell assay were used to examine the effects of circSETD2 overexpression or knockdown on liver cancer migration, invasion, cell cycle and cell proliferation. The tumourigenicity in vivo was utilized to assess the effect of circSETD2 on the proliferation of liver cancer cells. circSETD2 expression is lower in cell lines and liver cancer tissues. circSETD2 knockdown can considerably increase liver cancer cells' invasion, proliferation and colony formation. While In vitro and in vivo, circSETD2 overexpression shows opposite effect. Western blot showed that circSETD2 knockdown can considerably promote E-cadherin expression and inhibit Vimentin, N-cadherin, matrix metallopeptidase-9 (MMP-9) and MMP-2 expression. These findings improve our understanding of the mechanisms of liver cancer progression and will guide future development of therapeutic strategies against the disease by targeting circ-SETD2.