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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-89126-2 |
| _version_ | 1818430310047547392 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T15:31:22Z |
| format | Article |
| id | doaj.art-0f85e71fae9941418cd4c2ed466a26cd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:31:22Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0f85e71fae9941418cd4c2ed466a26cd2022-12-21T22:55:53ZengNature PortfolioScientific Reports2045-23222021-05-0111111510.1038/s41598-021-89126-2HNF1A regulates colorectal cancer progression and drug resistance as a downstream of POU5F1Shiki Fujino0Norikatsu Miyoshi1Aya Ito2Masayoshi Yasui3Chu Matsuda4Masayuki Ohue5Mamoru Uemura6Tsunekazu Mizushima7Yuichiro Doki8Hidetoshi Eguchi9Department of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Surgery, Osaka International Cancer InstituteDepartment of Surgery, Osaka International Cancer InstituteDepartment of Surgery, Osaka International Cancer InstituteDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41598-021-89126-2 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-89126-2 |
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