MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44

Abstract Tumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that are aberrantly regulated in cancer cells. This study aimed to determine the therapeutic potential of putative tumor suppressive miRNA, miR-138, agains...

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Autores principales:	Margaret Yeh, Yin-Ying Wang, Ji Young Yoo, Christina Oh, Yoshihiro Otani, Jin Muk Kang, Eun S. Park, Eunhee Kim, Sangwoon Chung, Young-Jun Jeon, George A. Calin, Balveen Kaur, Zhongming Zhao, Tae Jin Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8f6cf3c53d640d68b83a4e87dade76c
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spelling	oai:doaj.org-article:d8f6cf3c53d640d68b83a4e87dade76c2021-12-02T14:53:42ZMicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD4410.1038/s41598-021-88615-82045-2322https://doaj.org/article/d8f6cf3c53d640d68b83a4e87dade76c2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88615-8https://doaj.org/toc/2045-2322Abstract Tumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that are aberrantly regulated in cancer cells. This study aimed to determine the therapeutic potential of putative tumor suppressive miRNA, miR-138, against glioblastoma (GBM). Whole transcriptome and miRNA expression profiling analyses on human GBM patient tissues identified miR-138 as one of the significantly downregulated miRNAs with an inverse correlation with CD44 expression. Transient overexpression of miR-138 in GBM cells inhibited cell proliferation, cell cycle, migration, and wound healing capability. We unveiled that miR-138 negatively regulates the expression of CD44 by directly binding to the 3′ UTR of CD44. CD44 inhibition by miR-138 resulted in an inhibition of glioblastoma cell proliferation in vitro through cell cycle arrest as evidenced by a significant induction of p27 and its translocation into nucleus. Ectopic expression of miR-138 also increased survival rates in mice that had an intracranial xenograft tumor derived from human patient-derived primary GBM cells. In conclusion, we demonstrated a therapeutic potential of tumor suppressive miR-138 through direct downregulation of CD44 for the treatment of primary GBM.Margaret YehYin-Ying WangJi Young YooChristina OhYoshihiro OtaniJin Muk KangEun S. ParkEunhee KimSangwoon ChungYoung-Jun JeonGeorge A. CalinBalveen KaurZhongming ZhaoTae Jin LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Margaret Yeh Yin-Ying Wang Ji Young Yoo Christina Oh Yoshihiro Otani Jin Muk Kang Eun S. Park Eunhee Kim Sangwoon Chung Young-Jun Jeon George A. Calin Balveen Kaur Zhongming Zhao Tae Jin Lee MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
description	Abstract Tumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that are aberrantly regulated in cancer cells. This study aimed to determine the therapeutic potential of putative tumor suppressive miRNA, miR-138, against glioblastoma (GBM). Whole transcriptome and miRNA expression profiling analyses on human GBM patient tissues identified miR-138 as one of the significantly downregulated miRNAs with an inverse correlation with CD44 expression. Transient overexpression of miR-138 in GBM cells inhibited cell proliferation, cell cycle, migration, and wound healing capability. We unveiled that miR-138 negatively regulates the expression of CD44 by directly binding to the 3′ UTR of CD44. CD44 inhibition by miR-138 resulted in an inhibition of glioblastoma cell proliferation in vitro through cell cycle arrest as evidenced by a significant induction of p27 and its translocation into nucleus. Ectopic expression of miR-138 also increased survival rates in mice that had an intracranial xenograft tumor derived from human patient-derived primary GBM cells. In conclusion, we demonstrated a therapeutic potential of tumor suppressive miR-138 through direct downregulation of CD44 for the treatment of primary GBM.
format	article
author	Margaret Yeh Yin-Ying Wang Ji Young Yoo Christina Oh Yoshihiro Otani Jin Muk Kang Eun S. Park Eunhee Kim Sangwoon Chung Young-Jun Jeon George A. Calin Balveen Kaur Zhongming Zhao Tae Jin Lee
author_facet	Margaret Yeh Yin-Ying Wang Ji Young Yoo Christina Oh Yoshihiro Otani Jin Muk Kang Eun S. Park Eunhee Kim Sangwoon Chung Young-Jun Jeon George A. Calin Balveen Kaur Zhongming Zhao Tae Jin Lee
author_sort	Margaret Yeh
title	MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
title_short	MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
title_full	MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
title_fullStr	MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
title_full_unstemmed	MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
title_sort	microrna-138 suppresses glioblastoma proliferation through downregulation of cd44
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d8f6cf3c53d640d68b83a4e87dade76c
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MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44

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