Depletion of circ_0088046 suppressed cell growth and motility of hepatocellular carcinoma via circ_0088046‐miR‐1299‐RTKN2 ceRNA pathway

Abstract

AbstractCircular RNAs (circRNAs) have been verified to be important modulators and therapeutic targets of human hepatocellular carcinoma (HCC). This study aims to explore the role and mechanism of circ_0088046 in HCC progression. Quantitative real‐time polymerase chain reaction (qRT‐PCR), western blot and immunohistochemistry assays were used to detect the mRNA and protein expression of circ_0088046, miR‐1299, Rhotekin 2 (RTKN2), Bax, Bcl‐2, E‐cadherin and Ki‐67. Cell proliferation was investigated by 5‐Ethynyl‐2′‐deoxyuridine (EdU) assay and cell colony formation assay. Cell apoptosis rate was measured by flow cytometry. Transwell migration and invasion assays were adopted to assess cell migration and invasion. The molecular target relationship between miR‐1299 and circ_0088046 or RTKN2 were analysed by dual‐luciferase reporter assay and RNA immunoprecipitation assay. An animal experiment was conducted to demonstrate the effect of circ_0088046 on tumour formation in vivo. High levels of circ_0088046 and RTKN2, and low levels of miR‐1299 were displayed in HCC tissues and cells. Circ_0088046 absence repressed cell proliferation, migration and invasion, but boosted apoptosis of HCC cells. MiR‐1299 was a target of circ_0088046 and miR‐1299 inhibitor restored circ_0088046 silencing‐mediated inhibitory impacts on HCC cell malignancy. MiR‐1299 could directly target RTKN2, and overexpressed RTKN2 rescued the suppressive effects caused by miR‐1299 mimic. In addition, circ_0088046 silencing constrained tumour formation in vivo. Circ_0088046 contributed to HCC cell malignancy via modulating the miR‐1299/RTKN2 axis.