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miRNA-449a is downregulated in osteosarcoma and promotes cell apoptosis by targeting BCL2

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Tumor Biology

Abstract

Accumulating evidence reveals that miR-449a is expressed at a low level in several tumors and cancer cell lines, and acts as a tumor suppressor in several cancers. However, its role in osteosarcoma (OS) is not well understood. In the present study, we found that miR-449a was significantly downregulated in both OS tissues and cell lines. Furthermore, low expression level of miR-449a was correlated with advanced tumor stage, metastasis, and predicted a poor overall survival in OS patients. Additionally, restoration of miR-449a in OS cell lines U2OS and Saos-2 reduced cell viability, promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. Moreover, BCL2, an antiapoptotic molecule, was identified to be a direct target of miR-449a, and the proapoptotic function of miR-449a was mainly through targeting BCL2 expression. Taken together, our results demonstrated a tumor-suppressive role of miR-449a in OS progression and suggested a potential therapeutic target for OS.

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Acknowledgments

This project was supported by grants from the Natural Science Foundation of Shaanxi Province (No.2011k14-08-06).

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    Authors and Affiliations

    1. Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of **’an Jiaotong University, No. 157 **wu Road, **’an, Shaanxi, 710004, China

      Jie Chen, **song Zhou, **n Chen, Baohui Yang, Dong Wang, **lin Yang, ****g He & Haopeng Li

    2. Department of Orthopaedic Surgery, **’an No. 5 Hospital, **’an, Shaanxi, 710004, China

      **song Zhou

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    1. Jie Chen
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    Correspondence to Haopeng Li.

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    Jie Chen and **song Zhou contributed equally to this work.

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    Figure S1

    (A&B) hFOB 1.19 and NHOst cells were transfected with mimic control or miR-449a mimic as indicated. Cell viability was measured in the indicated time points post transfection using CCK-8 assay. (C&D) Cell apoptosis was detected 48 h post serum deprivation using Annexin V-FITC Apoptosis Detection Kit. (E) Expression of BCL2 in osteosarcoma cell lines and normal osteoblast cell lines were detected by Western blot. (GIF 29 kb)

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    Chen, J., Zhou, J., Chen, X. et al. miRNA-449a is downregulated in osteosarcoma and promotes cell apoptosis by targeting BCL2. Tumor Biol. 36, 8221–8229 (2015). https://doi.org/10.1007/s13277-015-3568-y

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