Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma
Abstract Background Receptor tyrosine kinase AXL has been found to be highly expressed in osteosarcoma and positively associated with poor prognosis. There are tumor groups with high or low AXL expression, which had different capabilities of invading vessels and forming distal metastases. Exosome‐tr...
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doaj-fe2d0375604b4621962063c70b2f8b752020-11-25T02:51:50ZengWileyCancer Medicine2045-76342020-09-019176354636610.1002/cam4.3303Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcomaQiming Li0Xuedi Wang1Nian Jiang2Xianbiao Xie3Ni Liu4JunFeng Liu5Jingnan Shen6Tingsheng Peng7Department of Pathology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaDepartment of Pathology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaDepartment of Pathology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaDepartment of Musculoskeletal Oncology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaDepartment of Pathology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaDepartment of Pathology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaDepartment of Musculoskeletal Oncology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaDepartment of Pathology First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaAbstract Background Receptor tyrosine kinase AXL has been found to be highly expressed in osteosarcoma and positively associated with poor prognosis. There are tumor groups with high or low AXL expression, which had different capabilities of invading vessels and forming distal metastases. Exosome‐transmitted lncRNA may be transferred intercellularly to promote tumor cells’ proliferation and invasion. Methods Exosomes were detected by electron microscopy, particle size analysis, and western blotting. High‐throughput sequencing helped to find the highest differentially expressed lncRNA in AXL‐associated exosomes. Clone formation, wound healing, transwell assay, and xenograft model in nude mice were performed to evaluate cells’ proliferation, migration, and invasion in vitro and in vivo. Lentiviral transfection was used to up‐ or down‐regulate the lncRNA levels in cell lines. Luciferase reporter assay and RNA FISH etchelped to indicate the molecular mechanisms. The results in the cell lines were proved in the osteosarcoma tissues with clinical analysis. Results The exosomes derived from donor cells with high AXL expression could promote the proliferation and invasion and upregulate AXL expression of the receiver cells with low AXL. Linc00852 was the highest differentially expressed lncRNA in AXL‐associated exosomes and was also regulated by AXL expression. Although the mechanisms of linc00852 in nucleus were unrevealed, it could upregulate AXL expression partly by competitively binding to miR‐7‐5p. The AXL‐exosome‐linc00852‐AXL positive feedback loop might exist between the donor cells and the receiver cells. Clinically, linc00852 was significantly highly expressed in osteosarcoma tissues and positively associated with tumor volumes and metastases, which was also obviously related with AXL mRNA expression. Conclusion AXL‐associated exosomal linc00852 up‐regulated the proliferation, migration, and invasion of osteosarcoma cells, which would be considered as a new tumor biomarker and a special therapeutic target for osteosarcoma.https://doi.org/10.1002/cam4.3303AXLexosomeinvasionlinc00852osteosarcoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qiming Li Xuedi Wang Nian Jiang Xianbiao Xie Ni Liu JunFeng Liu Jingnan Shen Tingsheng Peng |
spellingShingle |
Qiming Li Xuedi Wang Nian Jiang Xianbiao Xie Ni Liu JunFeng Liu Jingnan Shen Tingsheng Peng Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma Cancer Medicine AXL exosome invasion linc00852 osteosarcoma |
author_facet |
Qiming Li Xuedi Wang Nian Jiang Xianbiao Xie Ni Liu JunFeng Liu Jingnan Shen Tingsheng Peng |
author_sort |
Qiming Li |
title |
Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma |
title_short |
Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma |
title_full |
Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma |
title_fullStr |
Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma |
title_full_unstemmed |
Exosome‐transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma |
title_sort |
exosome‐transmitted linc00852 associated with receptor tyrosine kinase axl dysregulates the proliferation and invasion of osteosarcoma |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2020-09-01 |
description |
Abstract Background Receptor tyrosine kinase AXL has been found to be highly expressed in osteosarcoma and positively associated with poor prognosis. There are tumor groups with high or low AXL expression, which had different capabilities of invading vessels and forming distal metastases. Exosome‐transmitted lncRNA may be transferred intercellularly to promote tumor cells’ proliferation and invasion. Methods Exosomes were detected by electron microscopy, particle size analysis, and western blotting. High‐throughput sequencing helped to find the highest differentially expressed lncRNA in AXL‐associated exosomes. Clone formation, wound healing, transwell assay, and xenograft model in nude mice were performed to evaluate cells’ proliferation, migration, and invasion in vitro and in vivo. Lentiviral transfection was used to up‐ or down‐regulate the lncRNA levels in cell lines. Luciferase reporter assay and RNA FISH etchelped to indicate the molecular mechanisms. The results in the cell lines were proved in the osteosarcoma tissues with clinical analysis. Results The exosomes derived from donor cells with high AXL expression could promote the proliferation and invasion and upregulate AXL expression of the receiver cells with low AXL. Linc00852 was the highest differentially expressed lncRNA in AXL‐associated exosomes and was also regulated by AXL expression. Although the mechanisms of linc00852 in nucleus were unrevealed, it could upregulate AXL expression partly by competitively binding to miR‐7‐5p. The AXL‐exosome‐linc00852‐AXL positive feedback loop might exist between the donor cells and the receiver cells. Clinically, linc00852 was significantly highly expressed in osteosarcoma tissues and positively associated with tumor volumes and metastases, which was also obviously related with AXL mRNA expression. Conclusion AXL‐associated exosomal linc00852 up‐regulated the proliferation, migration, and invasion of osteosarcoma cells, which would be considered as a new tumor biomarker and a special therapeutic target for osteosarcoma. |
topic |
AXL exosome invasion linc00852 osteosarcoma |
url |
https://doi.org/10.1002/cam4.3303 |
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