Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma

Abstract Stemness factors control microRNA expression in cancer stem cells. Downregulation of miR-100 and miR-125b is associated with tumor progression and prognosis of various cancers. Comparing miRNA profiling of patient-derived tumorsphere (TS) and adherent (2D) hepatocellular carcinoma cells, mi...

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Autores principales:	Hyang Sook Seol, Yoshimitsu Akiyama, San-Eun Lee, Shu Shimada, Se Jin Jang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bde0dc7046044a5ebe4582a3fc80b476
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spelling	oai:doaj.org-article:bde0dc7046044a5ebe4582a3fc80b4762021-12-02T16:18:06ZLoss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma10.1038/s41598-020-77960-92045-2322https://doaj.org/article/bde0dc7046044a5ebe4582a3fc80b4762020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77960-9https://doaj.org/toc/2045-2322Abstract Stemness factors control microRNA expression in cancer stem cells. Downregulation of miR-100 and miR-125b is associated with tumor progression and prognosis of various cancers. Comparing miRNA profiling of patient-derived tumorsphere (TS) and adherent (2D) hepatocellular carcinoma cells, miR-100 and miR-125b are identified to have association with stemness. In TS cells, miR-100 and miR-125b were downregulated comparing to 2D cells. The finding was reproduced in Hep3B cells. Overexpression of stemness factors NANOG, OCT4 and SOX2 by introduction of gene constructs in Hep3B cells suppressed these two miRNA expression levels. Treatment of chromeceptin, an IGF signaling pathway inhibitor, decreased numbers of TS and inhibited the AKT/mTOR pathway. Stable cell line of miR-100 and miR-125b overexpression decreased IGF2 expression and inhibited tumor growth in the xenograft model. In conclusion, miR-100 and miR-125b have tumor suppressor role in hepatocellular carcinoma through inhibiting IGF2 expression and activation of the AKT/mTOR pathway.Hyang Sook SeolYoshimitsu AkiyamaSan-Eun LeeShu ShimadaSe Jin JangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyang Sook Seol Yoshimitsu Akiyama San-Eun Lee Shu Shimada Se Jin Jang Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma
description	Abstract Stemness factors control microRNA expression in cancer stem cells. Downregulation of miR-100 and miR-125b is associated with tumor progression and prognosis of various cancers. Comparing miRNA profiling of patient-derived tumorsphere (TS) and adherent (2D) hepatocellular carcinoma cells, miR-100 and miR-125b are identified to have association with stemness. In TS cells, miR-100 and miR-125b were downregulated comparing to 2D cells. The finding was reproduced in Hep3B cells. Overexpression of stemness factors NANOG, OCT4 and SOX2 by introduction of gene constructs in Hep3B cells suppressed these two miRNA expression levels. Treatment of chromeceptin, an IGF signaling pathway inhibitor, decreased numbers of TS and inhibited the AKT/mTOR pathway. Stable cell line of miR-100 and miR-125b overexpression decreased IGF2 expression and inhibited tumor growth in the xenograft model. In conclusion, miR-100 and miR-125b have tumor suppressor role in hepatocellular carcinoma through inhibiting IGF2 expression and activation of the AKT/mTOR pathway.
format	article
author	Hyang Sook Seol Yoshimitsu Akiyama San-Eun Lee Shu Shimada Se Jin Jang
author_facet	Hyang Sook Seol Yoshimitsu Akiyama San-Eun Lee Shu Shimada Se Jin Jang
author_sort	Hyang Sook Seol
title	Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma
title_short	Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma
title_full	Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma
title_fullStr	Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma
title_full_unstemmed	Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma
title_sort	loss of mir-100 and mir-125b results in cancer stem cell properties through igf2 upregulation in hepatocellular carcinoma
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/bde0dc7046044a5ebe4582a3fc80b476
work_keys_str_mv	AT hyangsookseol lossofmir100andmir125bresultsincancerstemcellpropertiesthroughigf2upregulationinhepatocellularcarcinoma AT yoshimitsuakiyama lossofmir100andmir125bresultsincancerstemcellpropertiesthroughigf2upregulationinhepatocellularcarcinoma AT saneunlee lossofmir100andmir125bresultsincancerstemcellpropertiesthroughigf2upregulationinhepatocellularcarcinoma AT shushimada lossofmir100andmir125bresultsincancerstemcellpropertiesthroughigf2upregulationinhepatocellularcarcinoma AT sejinjang lossofmir100andmir125bresultsincancerstemcellpropertiesthroughigf2upregulationinhepatocellularcarcinoma
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Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma

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