Abstract
BACKGROUND: This study aimed to verify the hypothesis that circular RNA MMP9 (circMMP9) promotes hepatocellular carcinoma (HCC) progression through targeting miR-149 and regulating cyclin D2 (CCND2) expression. METHODS: Expression of circMMP9, miR-149 and CCND2 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or protein blotting. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. The HCC cell migration and invasion were evaluated using wound healing and transwell assays. The interaction among circMMP9, miR-149, and CCND2 was evaluated using luciferase, RNA-pull down, and RNA immunoprecipitation (RIP) assays, respectively. Cell apoptosis and cycle were examined by flow cytometry. A subcutaneous HCC xenograft mouse model was established for analyzing the role of circMMP9 in regulating the progression of HCC in vivo. RESULTS: The expression of circMMP9 was elevated in HCC tissues and its high expression correlated with poor prognosis (P<0.05). Knockdown of circMMP9 restrained the proliferation, migration, and invasion of HCC cells and led to arrested cell cycle and increased apoptosis (all P<0.05). Furthermore, knockdown of circMMP9 attenuated HCC growth in vivo (P<0.05). Mechanically, circMMP9 acted as a sponge for miR-149 and enhanced CCND2 expression in HCC cells (P<0.05). Inhibition of miR-149 or overexpression of CCND2 abrogated knockdown of circMMP9-mediated alleviation of the malignant phenotypes of HCC (P<0.05). CONCLUSIONS: For the first time, we demonstrated that circMMP9 exacerbated HCC progression through the miR-149/CCND2 axis, which suggested that circMMP9 could be potentially targeted for HCC treatment.