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

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...

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Bibliographic Details
Published in:Molecular therapy Vol. 25; no. 9; pp. 2140 - 2149
Main Authors: Wang, Shu-Nan, Luo, Song, Liu, Chang, Piao, Zhenghao, Gou, Wenlong, Wang, Yun, Guan, Wei, Li, Qing, Zou, Hua, Yang, Zhen-Zhou, Wang, Dong, Wang, Yan, Xu, Meng, Jin, Hua, Xu, Cheng-Xiong
Format: Journal Article
Language:English
Published: United States Elsevier Inc 06.09.2017
Elsevier Limited
American Society of Gene & Cell Therapy
Subjects:
alpha-Crystallin B Chain - genetics
Apoptosis
Biomarkers
Bone cancer
Bone Neoplasms - drug therapy
Bone Neoplasms - genetics
Bone Neoplasms - mortality
Bone Neoplasms - pathology
Cell Line, Tumor
Cell Proliferation
Chemoresistance
Chemotherapy
Circulating MicroRNA
Cisplatin
Conflicts of interest
CRYAB
Crystallin
Drug Resistance, Neoplasm - genetics
Gene expression
Gene Expression Regulation, Neoplastic
Growth inhibition
Humans
Lung cancer
Lung Neoplasms - secondary
Lungs
Medical prognosis
Metastases
Metastasis
MicroRNAs - blood
MicroRNAs - genetics
miRNA
Neoplasm Metastasis
Neoplasm Staging
Original
Osteosarcoma
Osteosarcoma - drug therapy
Osteosarcoma - genetics
Osteosarcoma - mortality
Osteosarcoma - pathology
osteosarcoma metastasis
Patients
Prognosis
Proteins
RNA Interference
Sarcoma
Survival analysis
China
miRNA
chemoresistance
osteosarcoma metastasis
CRYAB
ISSN:1525-0016, 1525-0024, 1525-0024
Online Access:Get full text
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Summary: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. Wang et al. show that suppressed expression of miR-491 contributes to osteosarcoma (OS) lung metastasis and chemoresistance. In contrast, overexpression of miR-491 can inhibit OS lung metastasis and overcome chemoresistance, suggesting restoration of miR-491 is a novel strategy for treatment of OS lung metastasis and chemoresistance.
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These authors contributed equally to this work.
ISSN:1525-0016
1525-0024
1525-0024
DOI:10.1016/j.ymthe.2017.05.018