4.6 Article

Circ_0000527 promotes osteosarcoma cell progression through modulating miR-646/ARL2 axis

Journal

AGING-US
Volume 13, Issue 4, Pages 6091-6102

Publisher

IMPACT JOURNALS LLC

Keywords

osteosarcoma; circ_0000527; ARL2; miR-646

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Accumulating evidence indicates that circRNAs are crucial in the development of human tumors. In this study, circ_0000527 was found to be overexpressed in osteosarcoma cells, promoting cell growth and inflammatory mediator secretion by sponging miR-646 and modulating ARL2. The expression of miR-646 and ARL2 was dysregulated in osteosarcoma cells, and the level of circ_0000527 was negatively correlated with miR-646 expression in osteosarcoma specimens. The circ_0000527/miR-646/ARL2 axis may serve as a potential treatment target for osteosarcoma.
Accumulating evidence shows that circRNAs play critical roles in the development of human tumors. We observed that circ_0000527 was overexpressed in osteosarcoma cells (SAOS-2, HOS, MG-63 and U2OS) compared in hFOB1.19 cells. We demonstrated that the circ_0000527 level was higher in osteosarcoma specimens than in non-tumor specimens. The ectopic expression of circ_0000527 was shown to induce cell growth, cell cycle progression and the secretion of inflammatory mediators, including IL-1 beta, IL-6, IL-8 and TNF alpha. We demonstrated that circ_0000527 sponges miR-646 in osteosarcoma cells and that ARL2 is a target gene of miR-646. MiR-646 expression was decreased and ARL2 was overexpressed in osteosarcoma cells (SAOS-2, HOS, MG-63 and U2OS) compared to hFOB1.19 cells. Overexpression of circ_0000527 was demonstrated to induce ARL2 expression in MG-63 cells. We showed that miR-646 was downregulated in osteosarcoma specimens compared to that of non-tumor specimens and that the level of circ_0000527 was negatively correlated with miR-646 expression in osteosarcoma specimens. The elevated expression of circ_0000527 was shown to promote cell growth and cell cycle progression by modulating miR-646 expression. The ectopic expression of circ_0000527 was shown to promote cell growth, cell cycle progression and the secretion of inflammatory mediators by modulating ARL2. The present study suggested that the circ_0000527/miR-646/ARL2 axis may be a potential treatment target for osteosarcoma.

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