Abstract
Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. However, few studies have revealed the great value of circRNAs in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we performed experiments with the human OS cell lines and the results showed that the expression of circHIPK3 in OS cell lines was significantly upregulated compared to that in the normal cell line. In addition, the results showed that circHIPK3 could promote the migration, invasion, and growth of OS cells. Furthermore, miR-637 was identified as a target of circHIPK3, while STAT3 was targeted by miR-637. circHIPK3 could promote STAT3 expression via interacting with miR-637 in OS cells. In conclusion, our research uncovered an important role of the circHIPK3/miR-637/STAT3 pathway in the migration and invasion of OS cells and suggested that circHIPK3 may be a prognostic marker and a promising therapeutic target for OS.
Highlights
Osteosarcoma (OS) is a primary malignancy that develops in the long bones of the extremities [1]
It was found that circHIPK3 contained more than one binding site of multiple miRNAs, which could inhibit the activity of miRNA [24]
In oral squamous cell carcinoma, downregulation of the circHIPK3 gene can reduce the adsorption of miR-124, which can normally regulate the downstream target gene and suppress cancer cell growth [28]. circHIPK3 is an inhibitor of miR-4288 in nasopharyngeal carcinoma cells, which can inhibit the expression level of the latter, thereby enhancing the expression of ELF3 and promoting the malignant progress of nasopharyngeal carcinoma cells [26]
Summary
Osteosarcoma (OS) is a primary malignancy that develops in the long bones of the extremities [1]. With the development of technology and further research, various small molecules in cells have been found to be able to regulate cell activities [6, 7]. CircHIPK3 consists of two targeting sites of miR-558, and the binding between circHIPK3 and miR-558 could significantly inhibit the expression of heparinase, thereby reducing the invasion, migration, and angiogenesis of cancer cells [13]. CircHIPK3 can decrease miR-7 in colorectal cancer cells, promoting the growth, migration, and invasion. In vitro functional assay showed that circHIPK3 can promote the proliferation of osteosarcoma cells and enhance cell migration and invasion. We found that circHIPK3 could sponge on miR-637, significantly reducing the effect of miR-637 on its downstream gene STAT3, promoting the growth and spread of cancer cells
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