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

  • Daokun Gui
  • Hanqi CaoEmail author


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.


CDKN2B-AS1 miR-4458 MAP3K3 Osteosarcoma 



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

Funding information

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

Compliance with ethical standards

Conflict of interest

The authors declare that there are no competing interests.

Supplementary material

11626_2019_415_Fig6_ESM.png (185 kb)
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)

11626_2019_415_MOESM1_ESM.tif (9.7 mb)
High resolution image (TIF 9891 kb)
11626_2019_415_Fig7_ESM.png (191 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)

11626_2019_415_MOESM2_ESM.tif (4.8 mb)
High resolution image (TIF 4966 kb)


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Copyright information

© The Society for In Vitro Biology 2020

Authors and Affiliations

  1. 1.Department of OrthopaedicsLianshui County People’s HospitalJiangsu ProvinceChina
  2. 2.Department of OrthopaedicsThe Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anJiangsu ProvinceChina

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