HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2

Abstract Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data f...

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Main Authors: Peng Luo, Yan-dong Zhang, Feng He, Chang-jun Tong, Kai Liu, He Liu, Shi-zhuang Zhu, Jian-zhou Luo, Bing Yuan
Format: Article
Language:English
Published: Nature Portfolio 2022-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-13660-w
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author Peng Luo
Yan-dong Zhang
Feng He
Chang-jun Tong
Kai Liu
He Liu
Shi-zhuang Zhu
Jian-zhou Luo
Bing Yuan
author_facet Peng Luo
Yan-dong Zhang
Feng He
Chang-jun Tong
Kai Liu
He Liu
Shi-zhuang Zhu
Jian-zhou Luo
Bing Yuan
author_sort Peng Luo
collection DOAJ
description Abstract Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.
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spelling doaj.art-37149339bced41d7b6f8928904a6c3512022-12-22T03:34:01ZengNature PortfolioScientific Reports2045-23222022-06-0112111210.1038/s41598-022-13660-wHIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2Peng Luo0Yan-dong Zhang1Feng He2Chang-jun Tong3Kai Liu4He Liu5Shi-zhuang Zhu6Jian-zhou Luo7Bing Yuan8Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen HospitalGuangdong Medical UniversityDepartment of Orthopedics, Huazhong University of Science and Technology Union Shenzhen HospitalDepartment of Orthopedics, Huazhong University of Science and Technology Union Shenzhen HospitalDepartment of Orthopedic Surgery, The Third Hospital of Hebei Medical UniversityDepartment of Orthopedics, Huazhong University of Science and Technology Union Shenzhen HospitalDepartment of Orthopedics, Huazhong University of Science and Technology Union Shenzhen HospitalDepartment of Orthopedics, Huazhong University of Science and Technology Union Shenzhen HospitalDepartment of Orthopedics, The Fifth Hospital of Wuhan/The Second Affiliated Hospital of Jianghan UniversityAbstract Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.https://doi.org/10.1038/s41598-022-13660-w
spellingShingle Peng Luo
Yan-dong Zhang
Feng He
Chang-jun Tong
Kai Liu
He Liu
Shi-zhuang Zhu
Jian-zhou Luo
Bing Yuan
HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
Scientific Reports
title HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
title_full HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
title_fullStr HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
title_full_unstemmed HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
title_short HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
title_sort hif 1α mediated augmentation of mirna 18b 5p facilitates proliferation and metastasis in osteosarcoma through attenuation phf2
url https://doi.org/10.1038/s41598-022-13660-w
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