circHIPK3 promotes proliferation and migration and invasion via regulation of miR­637/HDAC4 signaling in osteosarcoma cells.

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 loss­of­function proliferation and Transwell assays, the present study revealed that circHIPK3­knockdown suppressed OS cell proliferation, migration and invasion. Furthermore, the present study screened potential microRNAs that may interact with circHIPK3. It was revealed that microRNA­637 (miR­637) expression was downregulated in OS according to a Gene Expression Omnibus data analysis. In addition, the present study demonstrated that miR­637 expression was downregulated in OS cell lines. A fluorescence in situ hybridization assay revealed that both miR­637 and circHIPK3 were located in the cytoplasm. An in­depth mechanism investigation demonstrated that circHIPK3 expression was inversely correlated with miR­637 expression, and that circHIPK3 was a target of miR­637. In addition, it was revealed that histone deacetylase 4 (HDAC4) was another downstream target gene of miR­637, as demonstrated using a luciferase assay. It was revealed that miR­637 suppressed OS cell proliferation, migration and invasion via targeting of HDAC4. Finally, the present study demonstrated that circHIPK3 sponged miR­637 to promote HDAC4 expression and OS cell proliferation, migration and invasion. In conclusion, the present study uncovered the role of the circHIPK3/miR­637/HDAC4 axis in OS cell proliferation, migration and invasion. It was demonstrated that circHIPK3 promoted OS cell proliferation, migration and invasion by modulating miR­637/HDAC4 signaling.