CircKDM1B promotes hepatocellular carcinoma progression through regulating miR-1322/PRC1 axis.

BACKGROUND: Circular RNA (circRNA) is considered an important molecular marker for the early diagnosis of tumors and a potential therapeutic target. Herein, we investigated the role and regulatory mechanism of circKDM1B in hepatocellular carcinoma (HCC).

METHODS: The expression of circKDM1B, miR-1322 and Protein regulator of cytokinesis 1 (PRC1) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) staining assays were performed to assess cell proliferation activity. Cell migration and invasion were detected by wound-healing scratch and transwell assay. Flow cytometry was used to analyze cell apoptosis. The protein levels of PCNA, MMP9, C-caspase3 and PRC1 were examined using western blot. The binding of circKDM1B and miR-1322 was verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull down assay.

RESULTS: CircKDM1B was overexpressed in HCC tissues and cells, and its overexpression was related to tumor stage and poor prognosis of HCC patients. Functionally, knockdown of circKDM1B suppressed proliferation, migration, invasion and promoted apoptosis of HCC cells. Mechanistically, circKDM1B functioned as ceRNA of miR-1322 to upregulate PRC1 in HCC cells. Overexpression of miR-1322 inhibited proliferation, migration, invasion and facilitated apoptosis of HCC cells, which was partly reversed by PRC1 overexpression. CircKDM1B knockdown impeded HCC tumor growth in vivo.

CONCLUSION: CircKDM1B played a critical role in HCC progression by regulating cell proliferation, migration, invasion and apoptosis. CircKDM1B/miR-1322/PRC1 axis might be a novel therapeutic target of HCC patients.