Circular RNA circ_0001955 promotes hepatocellular carcinoma tumorigenesis by up-regulating alkaline ceramidase 3 expression through microRNA-655-3p

Abstract

ABSTRACT The involvement of certain circular RNAs (circRNAs) in the development of hepatocellular carcinoma (HCC) has been reported. Herein, this study aimed to investigate the function and mechanism of circ_0001955 in HCC tumorigenesis. Expression of circ_0001955, miR-655-3p, and alkaline ceramidase 3 (ACER3) was evaluated by quantitative real-time PCR and Western blot. Cell counting kit-8, colony formation, transwell, tube formation, flow cytometry and tumor xenograft assays were adopted to perform in vitro and in vivo experiments. The direct interaction between miR-655-3p and circ_0001955 or ACER3 was verified using dual-luciferase reporter and RNA immunoprecipitation assays. Circ_0001955 was highly expression in HCC tissues and cells. Functionally, circ_0001955 deletion suppressed HCC tumorigenesis in vitro by suppressing cell growth, metastasis and angiogenesis. Mechanistically, circ_0001955 could competitively sponge miR-655-3p, which targeted ACER3. Besides that, miR-655-3p silencing abolished the anticancer action of circ_0001955 silencing on HCC cells. Moreover, miR-655-3p overexpression inhibited HCC cell oncogenic phenotypes mentioned above, which were attenuated by ACER3 up-regulation. Additionally, circ_0001955 knockdown also impeded HCC growth in a mouse model. In all, this study suggested a novel circ_0001955/miR-655-3p/ACER3 pathway in HCC progression.