LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis

Abstract The treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechan...

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Autores principales:	Shuhong Dai, Ning Li, Ming Zhou, Yue Yuan, Ding Yue, Tao Li, Xiaowei Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6aa9863a36664e7a871c350770d5c9e0
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spelling	oai:doaj.org-article:6aa9863a36664e7a871c350770d5c9e02021-12-02T13:51:16ZLncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis10.1038/s41598-021-81641-62045-2322https://doaj.org/article/6aa9863a36664e7a871c350770d5c9e02021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81641-6https://doaj.org/toc/2045-2322Abstract The treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3′-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR‐372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.Shuhong DaiNing LiMing ZhouYue YuanDing YueTao LiXiaowei ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shuhong Dai Ning Li Ming Zhou Yue Yuan Ding Yue Tao Li Xiaowei Zhang LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis
description	Abstract The treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3′-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR‐372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.
format	article
author	Shuhong Dai Ning Li Ming Zhou Yue Yuan Ding Yue Tao Li Xiaowei Zhang
author_facet	Shuhong Dai Ning Li Ming Zhou Yue Yuan Ding Yue Tao Li Xiaowei Zhang
author_sort	Shuhong Dai
title	LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis
title_short	LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis
title_full	LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis
title_fullStr	LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis
title_full_unstemmed	LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis
title_sort	lncrna ebln3p promotes the progression of osteosarcoma through modifying the mir-224-5p/rab10 signaling axis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6aa9863a36664e7a871c350770d5c9e0
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LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis

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