MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy

Abstract Chemotherapy is an important treatment modality for osteosarcoma. However, it often fails because of chemoresistance, especially multidrug resistance. Previously, we found several genes were involved in chemoresistance development. In this report, we used high-throughput microRNA (miRNA) ex...

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Autores principales:	Yichen Meng, Rui Gao, Jun Ma, Jianquan Zhao, Enjie Xu, Ce Wang, Xuhui Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d32b9d57a7b24b7ea1b380c178c61119
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spelling	oai:doaj.org-article:d32b9d57a7b24b7ea1b380c178c611192021-12-02T11:40:51ZMicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy10.1038/s41598-017-00405-32045-2322https://doaj.org/article/d32b9d57a7b24b7ea1b380c178c611192017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00405-3https://doaj.org/toc/2045-2322Abstract Chemotherapy is an important treatment modality for osteosarcoma. However, it often fails because of chemoresistance, especially multidrug resistance. Previously, we found several genes were involved in chemoresistance development. In this report, we used high-throughput microRNA (miRNA) expression analysis to reveal that expression of miR-140-5p was associated with chemosensitivity in osteosarcoma. The exact roles of miR-140-5p in the chemoresistance of osteosarcoma were then investigated, we found that knockdown of miR-140-5p enhanced osteosarcoma cells resistance to multiple chemotherapeutics while overexpression of miR-140-5p sensitized tumors to chemotherapy in vitro. Moreover, in vivo, knockdown of miR-140-5p also increased the osteosarcoma cells resistance to chemotherapy. Luciferase assay and Western blot analysis showed that HMGN5 was the direct target of miR-140-5p which could positively regulated autophagy. Silencing these target genes by siRNA or inhibition of autophagy sensitized osteosarcoma cells to chemotherapy. These findings suggest that a miR-140-5p/HMGN5/autophagy regulatory loop plays a critical role in chemoresistance in osteosarcoma. In conclusion, our data elucidated that miR-140-5p promoted autophagy mediated by HMGN5 and sensitized osteosarcoma cells to chemotherapy. These results suggest a potential application of miR-140-5p in overall survival, chemoresistance prognosis and treatment.Yichen MengRui GaoJun MaJianquan ZhaoEnjie XuCe WangXuhui ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yichen Meng Rui Gao Jun Ma Jianquan Zhao Enjie Xu Ce Wang Xuhui Zhou MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy
description	Abstract Chemotherapy is an important treatment modality for osteosarcoma. However, it often fails because of chemoresistance, especially multidrug resistance. Previously, we found several genes were involved in chemoresistance development. In this report, we used high-throughput microRNA (miRNA) expression analysis to reveal that expression of miR-140-5p was associated with chemosensitivity in osteosarcoma. The exact roles of miR-140-5p in the chemoresistance of osteosarcoma were then investigated, we found that knockdown of miR-140-5p enhanced osteosarcoma cells resistance to multiple chemotherapeutics while overexpression of miR-140-5p sensitized tumors to chemotherapy in vitro. Moreover, in vivo, knockdown of miR-140-5p also increased the osteosarcoma cells resistance to chemotherapy. Luciferase assay and Western blot analysis showed that HMGN5 was the direct target of miR-140-5p which could positively regulated autophagy. Silencing these target genes by siRNA or inhibition of autophagy sensitized osteosarcoma cells to chemotherapy. These findings suggest that a miR-140-5p/HMGN5/autophagy regulatory loop plays a critical role in chemoresistance in osteosarcoma. In conclusion, our data elucidated that miR-140-5p promoted autophagy mediated by HMGN5 and sensitized osteosarcoma cells to chemotherapy. These results suggest a potential application of miR-140-5p in overall survival, chemoresistance prognosis and treatment.
format	article
author	Yichen Meng Rui Gao Jun Ma Jianquan Zhao Enjie Xu Ce Wang Xuhui Zhou
author_facet	Yichen Meng Rui Gao Jun Ma Jianquan Zhao Enjie Xu Ce Wang Xuhui Zhou
author_sort	Yichen Meng
title	MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy
title_short	MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy
title_full	MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy
title_fullStr	MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy
title_full_unstemmed	MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy
title_sort	microrna-140-5p regulates osteosarcoma chemoresistance by targeting hmgn5 and autophagy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d32b9d57a7b24b7ea1b380c178c61119
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_version_	1718395547431206912

MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy

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