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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Vydáno v:	Molecular therapy Ročník 25; číslo 9; s. 2140 - 2149
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 06.09.2017 Elsevier Limited American Society of Gene & Cell Therapy
Témata:	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
On-line přístup:	Získat plný text
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work.
ISSN:	1525-0016 1525-0024 1525-0024
DOI:	10.1016/j.ymthe.2017.05.018