Abstract
Accumulating evidence has indicated that circular RNAs (circRNAs) serve crucial roles in the progression of a diverse range of different types of cancer, including osteosarcoma (OS). The present study determined the expression pattern and function of circRNA homeodomain interacting protein kinase 3 (circHIPK3), a novel circular RNA, in OS. It was revealed that circHIPK3 expression was upregulated in OS tissue samples and OS cell lines. A localization assay revealed that circHIPK3 was primarily located in the cytoplasm. Using loss‑of‑function proliferation and Transwell assays, the present study revealed that circHIPK3‑knockdown suppressed OS cell proliferation, migration and invasion. Furthermore, the present study screened potential microRNAs that may interact with circHIPK3. It was revealed that microRNA‑637 (miR‑637) expression was downregulated in OS according to a Gene Expression Omnibus data analysis. In addition, the present study demonstrated that miR‑637 expression was downregulated in OS cell lines. A fluorescence in situ hybridization assay revealed that both miR‑637 and circHIPK3 were located in the cytoplasm. An in‑depth mechanism investigation demonstrated that circHIPK3 expression was inversely correlated with miR‑637 expression, and that circHIPK3 was a target of miR‑637. In addition, it was revealed that histone deacetylase 4 (HDAC4) was another downstream target gene of miR‑637, as demonstrated using a luciferase assay. It was revealed that miR‑637 suppressed OS cell proliferation, migration and invasion via targeting of HDAC4. Finally, the present study demonstrated that circHIPK3 sponged miR‑637 to promote HDAC4 expression and OS cell proliferation, migration and invasion. In conclusion, the present study uncovered the role of the circHIPK3/miR‑637/HDAC4 axis in OS cell proliferation, migration and invasion. It was demonstrated that circHIPK3 promoted OS cell proliferation, migration and invasion by modulating miR‑637/HDAC4 signaling.