Cargando…

Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas

Lung is the primary site of osteosarcoma metastasis, but the underlying genetic or epigenetic factors determining lung metastasis of osteosarcoma are unknown. In this study, we report the status of growth arrest specific 5 (GAS5) in lung metastatic osteosarcomas. GAS5 was generally downregulated in...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Ying, Ren, Xue, Yuan, Ye, Yuan, Bao-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354213/
https://www.ncbi.nlm.nih.gov/pubmed/34386496
http://dx.doi.org/10.3389/fcell.2021.707693
_version_ 1783736554840129536
author Wang, Ying
Ren, Xue
Yuan, Ye
Yuan, Bao-Shan
author_facet Wang, Ying
Ren, Xue
Yuan, Ye
Yuan, Bao-Shan
author_sort Wang, Ying
collection PubMed
description Lung is the primary site of osteosarcoma metastasis, but the underlying genetic or epigenetic factors determining lung metastasis of osteosarcoma are unknown. In this study, we report the status of growth arrest specific 5 (GAS5) in lung metastatic osteosarcomas. GAS5 was generally downregulated in osteosarcoma patients (n = 24) compared to healthy controls (n = 10) and even more so in patients with lung metastatic disease(n = 11) compared to the patients without metastasis (n = 13). We also report a role of miR-21 in GAS5-mediated effects. Downregulation of GAS5 in hFOB 1.19 and U2OS osteosarcoma cells enhanced their migration and invasion, along with an upregulated epithelial–mesenchymal transition (EMT), as evidenced by downregulated E-cadherin and upregulated vimentin, ZEB1, and ZEB2. Downregulation of GAS5 also resulted in a significantly increased expression of miR-21. Moreover, downregulation of such elevated miR-21 was found to reverse the effects of GAS5 silencing. miR-21 was also found to be elevated in osteosarcoma patients with its levels particularly high in patients with lung metastasis. Our observations reveal a possible role of GAS5 and miR-21 in lung metastasis of osteosarcoma, presenting them as novel targets for therapy.
format Online
Article
Text
id pubmed-8354213
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-83542132021-08-11 Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas Wang, Ying Ren, Xue Yuan, Ye Yuan, Bao-Shan Front Cell Dev Biol Cell and Developmental Biology Lung is the primary site of osteosarcoma metastasis, but the underlying genetic or epigenetic factors determining lung metastasis of osteosarcoma are unknown. In this study, we report the status of growth arrest specific 5 (GAS5) in lung metastatic osteosarcomas. GAS5 was generally downregulated in osteosarcoma patients (n = 24) compared to healthy controls (n = 10) and even more so in patients with lung metastatic disease(n = 11) compared to the patients without metastasis (n = 13). We also report a role of miR-21 in GAS5-mediated effects. Downregulation of GAS5 in hFOB 1.19 and U2OS osteosarcoma cells enhanced their migration and invasion, along with an upregulated epithelial–mesenchymal transition (EMT), as evidenced by downregulated E-cadherin and upregulated vimentin, ZEB1, and ZEB2. Downregulation of GAS5 also resulted in a significantly increased expression of miR-21. Moreover, downregulation of such elevated miR-21 was found to reverse the effects of GAS5 silencing. miR-21 was also found to be elevated in osteosarcoma patients with its levels particularly high in patients with lung metastasis. Our observations reveal a possible role of GAS5 and miR-21 in lung metastasis of osteosarcoma, presenting them as novel targets for therapy. Frontiers Media S.A. 2021-07-27 /pmc/articles/PMC8354213/ /pubmed/34386496 http://dx.doi.org/10.3389/fcell.2021.707693 Text en Copyright © 2021 Wang, Ren, Yuan and Yuan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wang, Ying
Ren, Xue
Yuan, Ye
Yuan, Bao-Shan
Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas
title Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas
title_full Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas
title_fullStr Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas
title_full_unstemmed Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas
title_short Downregulated lncRNA GAS5 and Upregulated miR-21 Lead to Epithelial–Mesenchymal Transition and Lung Metastasis of Osteosarcomas
title_sort downregulated lncrna gas5 and upregulated mir-21 lead to epithelial–mesenchymal transition and lung metastasis of osteosarcomas
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354213/
https://www.ncbi.nlm.nih.gov/pubmed/34386496
http://dx.doi.org/10.3389/fcell.2021.707693
work_keys_str_mv AT wangying downregulatedlncrnagas5andupregulatedmir21leadtoepithelialmesenchymaltransitionandlungmetastasisofosteosarcomas
AT renxue downregulatedlncrnagas5andupregulatedmir21leadtoepithelialmesenchymaltransitionandlungmetastasisofosteosarcomas
AT yuanye downregulatedlncrnagas5andupregulatedmir21leadtoepithelialmesenchymaltransitionandlungmetastasisofosteosarcomas
AT yuanbaoshan downregulatedlncrnagas5andupregulatedmir21leadtoepithelialmesenchymaltransitionandlungmetastasisofosteosarcomas