HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1

Abstract POU5F1-expressing cells can self-renew and differentiate, contributing to metastasis formation in colorectal cancer (CRC), but it plays an important role in normal pluripotent stem cells. Here, we identified the CRC-specific gene, HNF1A, which is the downstream of POU5F1. HNF1A associates w...

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Autores principales:	Shiki Fujino, Norikatsu Miyoshi, Aya Ito, Masayoshi Yasui, Chu Matsuda, Masayuki Ohue, Mamoru Uemura, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f85e71fae9941418cd4c2ed466a26cd
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spelling	oai:doaj.org-article:0f85e71fae9941418cd4c2ed466a26cd2021-12-02T15:54:59ZHNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F110.1038/s41598-021-89126-22045-2322https://doaj.org/article/0f85e71fae9941418cd4c2ed466a26cd2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89126-2https://doaj.org/toc/2045-2322Abstract POU5F1-expressing cells can self-renew and differentiate, contributing to metastasis formation in colorectal cancer (CRC), but it plays an important role in normal pluripotent stem cells. Here, we identified the CRC-specific gene, HNF1A, which is the downstream of POU5F1. HNF1A associates with fatty acid and glucose metabolism, and CRC cells highly expressed it. In 198 CRC patients, high HNF1A expression was an independent predictor of disease-free (P = 0.031) and overall (P = 0.007) survival. HNF1A-knockdown showed significantly reduced cell growth, increased apoptosis, and improved anticancer drug sensitivity. We revealed that HNF1A regulated controlled GLUT1 expression via HIF1A and multidrug resistance protein function to suppress SRI. HNF1A expression was elevated in persister cells after exposure to anticancer drugs, and anticancer drug sensitivity was also improved in persister cells via the inhibition of HNF1A. In conclusion, HNF1A expression can reflect resistance to anticancer drug treatment, and its suppression improves anticancer drug sensitivity as a new therapeutic target.Shiki FujinoNorikatsu MiyoshiAya ItoMasayoshi YasuiChu MatsudaMasayuki OhueMamoru UemuraTsunekazu MizushimaYuichiro DokiHidetoshi EguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shiki Fujino Norikatsu Miyoshi Aya Ito Masayoshi Yasui Chu Matsuda Masayuki Ohue Mamoru Uemura Tsunekazu Mizushima Yuichiro Doki Hidetoshi Eguchi HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1
description	Abstract POU5F1-expressing cells can self-renew and differentiate, contributing to metastasis formation in colorectal cancer (CRC), but it plays an important role in normal pluripotent stem cells. Here, we identified the CRC-specific gene, HNF1A, which is the downstream of POU5F1. HNF1A associates with fatty acid and glucose metabolism, and CRC cells highly expressed it. In 198 CRC patients, high HNF1A expression was an independent predictor of disease-free (P = 0.031) and overall (P = 0.007) survival. HNF1A-knockdown showed significantly reduced cell growth, increased apoptosis, and improved anticancer drug sensitivity. We revealed that HNF1A regulated controlled GLUT1 expression via HIF1A and multidrug resistance protein function to suppress SRI. HNF1A expression was elevated in persister cells after exposure to anticancer drugs, and anticancer drug sensitivity was also improved in persister cells via the inhibition of HNF1A. In conclusion, HNF1A expression can reflect resistance to anticancer drug treatment, and its suppression improves anticancer drug sensitivity as a new therapeutic target.
format	article
author	Shiki Fujino Norikatsu Miyoshi Aya Ito Masayoshi Yasui Chu Matsuda Masayuki Ohue Mamoru Uemura Tsunekazu Mizushima Yuichiro Doki Hidetoshi Eguchi
author_facet	Shiki Fujino Norikatsu Miyoshi Aya Ito Masayoshi Yasui Chu Matsuda Masayuki Ohue Mamoru Uemura Tsunekazu Mizushima Yuichiro Doki Hidetoshi Eguchi
author_sort	Shiki Fujino
title	HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1
title_short	HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1
title_full	HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1
title_fullStr	HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1
title_full_unstemmed	HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1
title_sort	hnf1a regulates colorectal cancer progression and drug resistance as a downstream of pou5f1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0f85e71fae9941418cd4c2ed466a26cd
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HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1

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