Circular RNA 0001785 regulates the pathogenesis of osteosarcoma as a ceRNA by sponging miR-1200 to upregulate HOXB2

环状 RNA 0001785 作为 ceRNA 通过吸收 miR-1200 上调 HOXB2 来调控骨肉瘤的发病机制

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作者:Shenglong Li, Yi Pei, Wei Wang, Fei Liu, Ke Zheng, Xiaojing Zhang

Abstract

Circular RNAs (circRNAs) are recently emerged to be promising therapeutic targets of tumors. Osteosarcoma is the most prevalent primary bone tumor and the third most prevalent cancer in children and adolescents. This study firstly analyzed circRNA microarray of osteosarcoma and selected circ-0001785 as the study object. We aimed to comprehensively investigate the expression pattern and biological function of circ-0001785 in the progression of osteosarcoma. Relative levels of circ-0001785 and miR-1200 in the normal human osteoblast cell line and osteosarcoma cell lines were determined. Bioinformatics analyses predicted the binding relationship between miR-1200 to HOXB2 and circ-0001785, while dual-luciferase reporter gene assay further verified this relationship. Flow cytometry and EdU assay were used for evaluating the regulatory effects of circ-0001785/miR-1200/HOXB2 axis on osteosarcoma cells. Consistent with the microarray analysis, circ-0001785 was highly expressed in osteosarcoma cell lines. Knockdown of circ-0001785 attenuated proliferative ability, but induced the apoptosis of osteosarcoma cells. Furthermore, we confirmed that circ-0001785 competitively bound to miR-1200, thus up-regulating its target gene HOXB2. Western blot analyses revealed that circ-0001785 regulated the PI3K/Akt signaling and Bcl-2 family pathway in osteosarcoma. In conclusion, circ-0001785 regulates the pathogenesis of osteosarcoma by sponging miR-1200 to up-regulate HOXB2 expression.

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