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Mol Ther. 2017 Sep 6;25(9):2140-2149. doi: 10.1016/j.ymthe.2017.05.018. Epub 2017 Jun 23.

miR-491 Inhibits Osteosarcoma Lung Metastasis and Chemoresistance by Targeting αB-crystallin.

Author information

1
Department of Radiology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
2
Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
3
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China.
4
Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China.
5
Department of Orthopaedics, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
6
Department of Pathology, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
7
Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
8
Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China; Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA. Electronic address: jinhua12001@hanamil.net.
9
Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. Electronic address: xuchengxiong@hanmail.net.

Abstract

Dysregulated microRNAs (miRNAs) play an important role in osteosarcoma (OS) progression. In the present study, we investigate the clinical significance of serum miR-491 level and the potential role of miR-491 in OS lung metastasis and chemoresistance. Clinical data show that the level of miR-491 was decreased in serum from OS patients compared with healthy control subjects, and that a decreased serum miR-491 level is correlated with increased metastasis, poor chemoresponse, and lower survival rate in OS patients. In vitro and in vivo experiments show that overexpression of miR-491 suppresses OS cell lung metastasis, whereas it enhances cisplatin (CDDP)-induced tumor growth inhibition and apoptosis. In contrast, inhibition of miR-491 stimulates OS cell lung metastasis and suppresses CDDP-induced tumor growth inhibition and apoptosis. Furthermore, we demonstrate that miR-491 exerts its role by directly targeting αB-crystallin (CRYAB) in OS. Our findings suggest that serum level of miR-491 has potential as a biomarker for predicting OS progression and prognosis of OS patients. Additionally, restoration of miR-491 may be a novel strategy for inhibiting OS lung metastasis and overcoming OS cell resistance to chemotherapy.

KEYWORDS:

CRYAB; chemoresistance; miRNA; osteosarcoma metastasis

PMID:
28648665
PMCID:
PMC5589150
DOI:
10.1016/j.ymthe.2017.05.018
[Indexed for MEDLINE]
Free PMC Article

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