CircUBAP2 regulates osteosarcoma progression via the miR‑204‑3p/HMGA2 axis

Abstract

Circular RNA (circRNA/circ)-ubiquitin associated protein 2 (UBAP2), a newly recognized circRNA, serves a functional role in several types of tumor, including ovarian cancer, colorectal cancer and osteosarcoma. However, the precise roles and molecular mechanism under-lying circUBAP2 in osteosarcoma (OS) are not completely understood. In the present study, the expression levels of circUBAP2, microRNA (miR)-204-3p and (HMGA2) were evaluated via reverse transcription-quantitative PCR in OS tissues and cells. OS cell proliferation, migration, invasion and apoptosis were assessed by performing Cell Counting Kit-8, Transwell and flow cytometry assays, respectively. HMGA2 protein expression levels were determined via western blot-ting. Dual-luciferase reporter assays were performed to verify the interaction between circUBAP2 and miR-204-3p, and between miR-204-3p and HMGA2. An RNA immunoprecipitation (RIP) assay was conducted to confirm the interaction between circUBAP2 and miR-204-3p. The results demonstrated that circUBAP2 expression was significantly upregulated in OS tissues and cell lines compared with para-cancerous tissues and hFOB1.19 cells, respectively. In addition, high circUBAP2 expression levels in patients with OS were associated with a lower survival rate compared with lower expression levels in patients with OS. The functional assays revealed that circUBAP2 knockdown significantly inhibited OS cell proliferation, migration and invasion, but increased OS cell apoptosis compared with the small interfering RNA-negative control (si-NC) group. The dual-luciferase reporter and RIP assay results confirmed that circUBAP2 bound to miR-204-3p. Moreover, miR-204-3p expression was significantly downregulated in OS tissues compared with paracancerous tissues, and miR-204-3p expression was negatively correlated with circUBAP2 expression in OS tissues. Collectively, the results demonstrated that miR-204-3p was associated with circUBAP2 knockdown-mediated inhibition of OS cell malignant behavior. Moreover, miR-204-3p was also identified as one of the direct targets of HMGA2. Collectively, the results indicated that compared with the si-NC group, circUBAP2 knockdown significantly inhibited OS cell malignant behavior by binding to miR-204-3p, which subsequently regulated HMGA2 expression. Therefore, the present study demonstrated that circUBAP2 expression was upregulated in OS, and circUBAP2 regulated OS cell malignant behavior via the miR-204-3p/HMGA2 axis.