Long non-coding RNA CCAT1 regulates the biological behavior of osteosarcoma cells through the miR-454-3p/ZEB2 axis

T. Su, S.-D. Zhang, J. Zhao

Pediatric Surgery, Jining No. 1 People’s Hospital, Jining, P.R. China. zhaojuan@126.com

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• Oncology

OBJECTIVE: To investigate the clinical value and mechanism of action of lncRNA CCAT1 in OS.

PATIENTS AND METHODS: Serum, tumor tissue and corresponding adjacent tissue of 84 cases of patients receiving treatment in our hospital from February 2014 to June 2015 were obtained. Healthy volunteers were recruited during the same period for serum collection. CCAT1 expression in serum and tissue samples, were detected, and the value of its expression in osteosarcoma (OS) diagnosis and prognosis was analyzed. Stable and transient over-expression and inhibition vectors were established and transfected into OS cells. CCK-8, transwell, and flow cytometry were applied to determine the proliferation, invasion, and apoptosis of transfected cells, and the Dual-Luciferase reporter was utilized to determine the correlation of CCAT1 with miR-454-3p, miR-454-3p, and ZEB2 (zinc-finger E-box-binding homeobox-2).

RESULTS: In OS, CCAT1 was upregulated, and serum CCAT1 could be used as a marker for OS diagnosis, with an AUC value of 0.930. High CCAT1 expression predicted poor survival rate in patients. Inhibition of CCAT1 could suppress the proliferation and invasion of OS cells, and increase the apoptosis rate. Over-expression of miR-454-3p and inhibition of ZEB2 could also achieve the above effects. Dual-Luciferase reporter indicated that CCAT1 could target miR-454-3p, and miR-454-3p could target ZEB2. The rescue experiment proved that CCAT1 could regulate OS progression through the miR-454-3p/ZEB2 axis.

CONCLUSIONS: CCAT1 can be used as a diagnostic and prognostic marker for OS, promote OS cell proliferation and invasion, and inhibit apoptosis through the miR-454-3p/ZEB2 axis, which can be a therapeutic target for OS.

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