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Long non-coding RNA CDKN2B-AS1 promotes osteosarcoma by increasing the expression of MAP3K3 via sponging miR-4458

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Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor worldwide. Recently, several studies have shown that the long non-coding RNA (lncRNA) CDKN2B-AS1 plays a critical role in several cancers. However, the function and underlying mechanism of CDKN2B-AS1 in OS development remains elusive. In this study, we firstly assessed the expression of CDKN2B-AS1 in OS tissues and cells, showing that CDKN2B-AS1 expression were remarkably upregulated in OS tissues and cells. Moreover, CDKN2B-AS1 knockdown suppressed cell proliferation, migration, and EMT progress in OS. Interestingly, we found and proved that CDKN2B-AS1 could sponge miR-4458 in OS cells. Moreover, MAP3K3 was certified as a downstream target of miR-4458 in OS. Besides, MAP3K3 was negatively regulated by miR-4458 and positively regulated by CDKN2B-AS1. More importantly, overexpression of MAP3K3 could partly counteract the effect of CDKN2B-AS1 suppression on the biological behavior of OS cells. Also, the in vivo experiments further testified that CDKN2B-AS1 accelerated tumor growth in OS. Our results suggested that CDKN2B-AS1 facilitated OS progression by sponging miR-4458 to enhance MAP3K3 expression, which provides a novel insight into improving diagnostic and therapeutic strategies for patients with OS.

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Acknowledgments

We sincerely appreciate lab members for their support to our research.

Funding

This research was supported by grants from Jiangsu Natural Science Foundation (BK20171265) and the Huai’an Key laboratory funded projects (HAP201608).

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Authors and Affiliations

  1. Department of Orthopaedics, Lianshui County People’s Hospital, No. 6, Hongri Avenue, Lianshui County, Jiangsu Province, 223400, China

    Daokun Gui

  2. Department of Orthopaedics, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, No.62, Huaihai Road (S.), Huaian, Jiangsu Province, 223002, China

    Hanqi Cao

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  1. Daokun Gui
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  2. Hanqi Cao
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Correspondence to Hanqi Cao.

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Editor: Tetsuji Okamoto

Electronic supplementary material

Supplementary Fig. 1

Quantitative figures of western blot assay in the study. (A) Quantitative figure of western blot assay in Fig. 1H. (B) Quantitative figure of western blot assay in Fig. 3D. (C) Quantitative figure of western blot assay in Fig. 4F. *P < 0.05. (PNG 185 kb)

High resolution image (TIF 9891 kb)

Supplementary Fig. 2

The location of target sites between miR-4458 and CDKN2B-AS1/ MAP3K3. (A-B) the location of putative binding sites for miR4458 in full length of CDKN2B-AS1 or 3’UTR of MAP3K3 was displayed. (PNG 190 kb)

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Gui, D., Cao, H. Long non-coding RNA CDKN2B-AS1 promotes osteosarcoma by increasing the expression of MAP3K3 via sponging miR-4458. In Vitro Cell.Dev.Biol.-Animal 56, 24–33 (2020). https://doi.org/10.1007/s11626-019-00415-7

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  • DOI: https://doi.org/10.1007/s11626-019-00415-7

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