Circ_0000515 drives the progression of hepatocellular carcinoma by regulating MAPK10

H. Li, C.-M. Li, R. Yuan, H.-B. Wang, J. Wei

Department of Liver and Infectious Diseases, Liver Disease Research Center, the Second People’s Hospital of Yunnan Province, Kunming, China. wejia@aliyun.com

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• Oncology

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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