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Upregulation of circular RNA circ_0000502 predicts unfavorable prognosis in osteosarcoma and facilitates cell progression via sponging miR-1238
Authors:Hongfei Qi  Yue Sun  Yuehong Jiang  Xiaolin Li
Institution:1. Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

Hongfei Qia and Yue Sun contributed equally to this study.;2. Department of Education, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

Hongfei Qia and Yue Sun contributed equally to this study.;3. Department of Clinical laboratory, Heilongjiang Provincial Hospital, Harbin, China;4. Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China

Abstract:Growing evidence suggests that circular RNAs (circRNAs) play a significant role in regulating cancer initiation and metastasis. Osteosarcoma (OS) is a sophisticated disease with various genes activated or silenced. In this study, we defined a novel cancer-related circRNA, circ_0000502 in OS progression. qRT-PCR was conducted to detect its expression level in OS tissue samples and cell lines. In addition, the clinical significance of circ_0000502 was investigated. Afterwards, gain-of-function and loss-of-function in vitro assays were performed to detect the cell growth, apoptosis, migration, and invasion altered by circ_0000502 by CCK-8, clone-forming, flow cytometry, and transwell experiments. Xenograft study was performed to validate the in vitro data. The luciferase reporter assay was used to explore the mechanism of circ_0000502. Circ_0000502 was identified upregulated in both OS tissue specimens and cells. In addition, its expression predicts clinical severity and unfavorable prognosis in the 63 recruited patients with OS. Circ_0000502 facilitated cell proliferation, migration, and invasion in OS cells and inhibited cell apoptosis. The animal study further confirmed the in vitro results. For mechanism exploration, circ_0000502 could directly sponge microRNA (miR)-1238, and the oncogenic functions of circ_0000502 is partially dependent on its regulation of miR-1238 proved by rescue assays. In summary, this study might help to develop rational predictive and therapeutic target for patients with OS.
Keywords:circ_0000502  circular RNA  miR-1238  osteosarcoma  prognosis
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