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 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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Elsevier Inc
06.09.2017
Elsevier Limited American Society of Gene & Cell Therapy |
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| ISSN: | 1525-0016, 1525-0024, 1525-0024 |
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| 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.
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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| AbstractList | 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. 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.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. 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. 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. 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. |
| Author | Zou, Hua Luo, Song Wang, Shu-Nan Li, Qing Wang, Dong Jin, Hua Wang, Yan Xu, Cheng-Xiong Yang, Zhen-Zhou Gou, Wenlong Wang, Yun Piao, Zhenghao Guan, Wei Liu, Chang Xu, Meng |
| AuthorAffiliation | 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 5 Department of Orthopaedics, 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 9 Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA 7 Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China 1 Department of Radiology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China 4 Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China 6 |
| AuthorAffiliation_xml | – name: 8 Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – name: 6 Department of Pathology, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China – name: 5 Department of Orthopaedics, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – name: 7 Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – name: 1 Department of Radiology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – name: 3 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China – name: 2 Department of Orthopaedics, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China – name: 4 Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China – name: 9 Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA |
| Author_xml | – sequence: 1 givenname: Shu-Nan surname: Wang fullname: Wang, Shu-Nan organization: Department of Radiology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 2 givenname: Song surname: Luo fullname: Luo, Song organization: Department of Orthopaedics, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China – sequence: 3 givenname: Chang surname: Liu fullname: Liu, Chang organization: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China – sequence: 4 givenname: Zhenghao surname: Piao fullname: Piao, Zhenghao organization: Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Hangzhou 310036, China – sequence: 5 givenname: Wenlong surname: Gou fullname: Gou, Wenlong organization: Department of Orthopaedics, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 6 givenname: Yun surname: Wang fullname: Wang, Yun organization: Department of Pathology, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China – sequence: 7 givenname: Wei surname: Guan fullname: Guan, Wei organization: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 8 givenname: Qing surname: Li fullname: Li, Qing organization: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 9 givenname: Hua surname: Zou fullname: Zou, Hua organization: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 10 givenname: Zhen-Zhou surname: Yang fullname: Yang, Zhen-Zhou organization: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 11 givenname: Dong surname: Wang fullname: Wang, Dong organization: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 12 givenname: Yan surname: Wang fullname: Wang, Yan organization: Department of Orthopaedics, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China – sequence: 13 givenname: Meng surname: Xu fullname: Xu, Meng organization: Department of Orthopaedics, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China – sequence: 14 givenname: Hua surname: Jin fullname: Jin, Hua email: jinhua12001@hanamil.net organization: Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China – sequence: 15 givenname: Cheng-Xiong surname: Xu fullname: Xu, Cheng-Xiong email: xuchengxiong@hanmail.net organization: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China |
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| Copyright | 2017 The American Society of Gene and Cell Therapy Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved. 2017. The American Society of Gene and Cell Therapy 2017 The American Society of Gene and Cell Therapy. 2017 The American Society of Gene and Cell Therapy |
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| Keywords | miRNA chemoresistance osteosarcoma metastasis CRYAB |
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| Snippet | Dysregulated microRNAs (miRNAs) play an important role in osteosarcoma (OS) progression. In the present study, we investigate the clinical significance of... |
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| SubjectTerms | 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 |
| Title | miR-491 Inhibits Osteosarcoma Lung Metastasis and Chemoresistance by Targeting αB-crystallin |
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