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The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway
Increasing evidence demonstrates that Lin28B plays critical roles in numerous biological processes including cell proliferation and stemness maintenance. However, the molecular mechanisms underlying Lin28B nuclear translocation remain poorly understood. Here, we found for the first time that KRAS pr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782082/ https://www.ncbi.nlm.nih.gov/pubmed/33107691 http://dx.doi.org/10.1002/1878-0261.12836 |
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author | Liu, Yawen Wang, Dawei Zhou, Meng Chen, Hui Wang, Huizhi Min, Jingyu Chen, Jiaxi Wu, Shuhui Ni, Xiufan Zhang, Youli Gong, Aihua Xu, Min |
author_facet | Liu, Yawen Wang, Dawei Zhou, Meng Chen, Hui Wang, Huizhi Min, Jingyu Chen, Jiaxi Wu, Shuhui Ni, Xiufan Zhang, Youli Gong, Aihua Xu, Min |
author_sort | Liu, Yawen |
collection | PubMed |
description | Increasing evidence demonstrates that Lin28B plays critical roles in numerous biological processes including cell proliferation and stemness maintenance. However, the molecular mechanisms underlying Lin28B nuclear translocation remain poorly understood. Here, we found for the first time that KRAS promoted Lin28B nuclear translocation through PKCβ, which directly bound to and phosphorylated Lin28B at S243. Firstly, we observed that Lin28B was upregulated in pancreatic cancer, contributing to cellular migration and proliferation. Furthermore, nuclear Lin28B upregulated TET3 messenger RNA and protein levels by blocking the production of mature let‐7i. Subsequently, increased TET3 expression could also promote the expression of Lin28B, thereby forming a Lin28B/let‐7i/TET3 feedback loop. Our results suggest that the KRAS/Lin28B axis drives the let‐7i/TET3 pathway to maintain the stemness of pancreatic cancer cells. These findings illuminate the distinct mechanism of Lin28B nuclear translocation and its important roles in KRAS‐driven pancreatic cancer, and have important implications for development of novel therapeutic strategies for this cancer. |
format | Online Article Text |
id | pubmed-7782082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77820822021-01-08 The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway Liu, Yawen Wang, Dawei Zhou, Meng Chen, Hui Wang, Huizhi Min, Jingyu Chen, Jiaxi Wu, Shuhui Ni, Xiufan Zhang, Youli Gong, Aihua Xu, Min Mol Oncol Research Articles Increasing evidence demonstrates that Lin28B plays critical roles in numerous biological processes including cell proliferation and stemness maintenance. However, the molecular mechanisms underlying Lin28B nuclear translocation remain poorly understood. Here, we found for the first time that KRAS promoted Lin28B nuclear translocation through PKCβ, which directly bound to and phosphorylated Lin28B at S243. Firstly, we observed that Lin28B was upregulated in pancreatic cancer, contributing to cellular migration and proliferation. Furthermore, nuclear Lin28B upregulated TET3 messenger RNA and protein levels by blocking the production of mature let‐7i. Subsequently, increased TET3 expression could also promote the expression of Lin28B, thereby forming a Lin28B/let‐7i/TET3 feedback loop. Our results suggest that the KRAS/Lin28B axis drives the let‐7i/TET3 pathway to maintain the stemness of pancreatic cancer cells. These findings illuminate the distinct mechanism of Lin28B nuclear translocation and its important roles in KRAS‐driven pancreatic cancer, and have important implications for development of novel therapeutic strategies for this cancer. John Wiley and Sons Inc. 2020-11-28 2021-01 /pmc/articles/PMC7782082/ /pubmed/33107691 http://dx.doi.org/10.1002/1878-0261.12836 Text en © 2020 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Liu, Yawen Wang, Dawei Zhou, Meng Chen, Hui Wang, Huizhi Min, Jingyu Chen, Jiaxi Wu, Shuhui Ni, Xiufan Zhang, Youli Gong, Aihua Xu, Min The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway |
title | The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway |
title_full | The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway |
title_fullStr | The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway |
title_full_unstemmed | The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway |
title_short | The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let‐7i/TET3 pathway |
title_sort | kras/lin28b axis maintains stemness of pancreatic cancer cells via the let‐7i/tet3 pathway |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782082/ https://www.ncbi.nlm.nih.gov/pubmed/33107691 http://dx.doi.org/10.1002/1878-0261.12836 |
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