Circ_0000515 drives the progression of hepatocellular carcinoma by regulating MAPK10.
2020
OBJECTIVE To explore the expression pattern and clinical significance of circ_0000515 in hepatocellular carcinoma (HCC), as well as the molecular mechanism. PATIENTS AND METHODS Fifty HCC patients were recruited, and their cancer tissues and adjacent normal ones were collected for detecting the differential expression of circ_0000515. The relationship between circ_0000515 and clinical parameters in HCC patients was analyzed. Circ_0000515 knockdown model was generated by lentivirus transfection in Hep3B and MHCC88H cells that were highly expressed with circ_0000515. Regulatory effects of circ_0000515 on phenotypes of Hep3B and MHCC88H cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assay. Target gene of circ_0000515 was verified by Dual-Luciferase reporter assay, and its involvement in HCC progression was detected by rescue experiments. In vivo xenograft model was generated in nude mice aiming to elucidate the role of circ_0000515 in regulating HCC growth. RESULTS Circ_0000515 was highly expressed in HCC tissues and cell lines. High level of circ_0000515 predicted advanced stage, high incidence of lymphatic metastasis, and low disease-free survival and overall survival in HCC. Knockdown of circ_0000515 attenuated proliferative and migratory abilities in Hep3B and MHCC88H cells. MAPK10, as the target gene binding circ_0000515, was negatively regulated by circ_0000515. Rescue experiments and in vivo xenograft model both indicated that circ_0000515 aggravated the malignant progression of HCC by targeting MAPK10. CONCLUSIONS Circ_0000515 is upregulated in HCC tissues and cell lines. It can be used for predicting tumor staging, lymphatic metastasis, and prognosis in HCC. Circ_0000515 aggravates the malignant progression of HCC by downregulating MAPK10.
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