Cargando…
DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1
Let-7 miRNAs act as tumour suppressors by directly binding to the 3′UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For exam...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459849/ https://www.ncbi.nlm.nih.gov/pubmed/25702703 http://dx.doi.org/10.1111/jcmm.12522 |
_version_ | 1782375281009360896 |
---|---|
author | Sun, Xin Tang, Shou-Ching Xu, Chongwen Wang, Chenguang Qin, Sida Du, Ning Liu, Jian Zhang, Yiwen Li, Xiang Luo, Gang Zhou, Jie Xu, Fei Ren, Hong |
author_facet | Sun, Xin Tang, Shou-Ching Xu, Chongwen Wang, Chenguang Qin, Sida Du, Ning Liu, Jian Zhang, Yiwen Li, Xiang Luo, Gang Zhou, Jie Xu, Fei Ren, Hong |
author_sort | Sun, Xin |
collection | PubMed |
description | Let-7 miRNAs act as tumour suppressors by directly binding to the 3′UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback relationship is Dicer, a central regulator of miRNA expression through sequence-specific silencing. We first identified that DICER1 is the key downstream gene for cyclin D1-induced let-7 expression. In addition, we found that let-7 miRNAs expression decreased because of the p53-induced cell death response, with deregulated cyclin D1. Our results also showed that cyclin D1 is required for Nutlin-3 and TAX-induced let-7 expression in cancer repression and the cell death response. For the first time, we provide evidence that let-7 and cyclin D1 form a feedback loop in regulating therapy response of cancer cells and cancer stem cells, and importantly, that alteration of let-7 expression, mainly caused by cyclin D1, is a sensitive indicator for better chemotherapies response. |
format | Online Article Text |
id | pubmed-4459849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-44598492015-06-16 DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1 Sun, Xin Tang, Shou-Ching Xu, Chongwen Wang, Chenguang Qin, Sida Du, Ning Liu, Jian Zhang, Yiwen Li, Xiang Luo, Gang Zhou, Jie Xu, Fei Ren, Hong J Cell Mol Med Original Articles Let-7 miRNAs act as tumour suppressors by directly binding to the 3′UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback relationship is Dicer, a central regulator of miRNA expression through sequence-specific silencing. We first identified that DICER1 is the key downstream gene for cyclin D1-induced let-7 expression. In addition, we found that let-7 miRNAs expression decreased because of the p53-induced cell death response, with deregulated cyclin D1. Our results also showed that cyclin D1 is required for Nutlin-3 and TAX-induced let-7 expression in cancer repression and the cell death response. For the first time, we provide evidence that let-7 and cyclin D1 form a feedback loop in regulating therapy response of cancer cells and cancer stem cells, and importantly, that alteration of let-7 expression, mainly caused by cyclin D1, is a sensitive indicator for better chemotherapies response. BlackWell Publishing Ltd 2015-06 2015-02-20 /pmc/articles/PMC4459849/ /pubmed/25702703 http://dx.doi.org/10.1111/jcmm.12522 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Sun, Xin Tang, Shou-Ching Xu, Chongwen Wang, Chenguang Qin, Sida Du, Ning Liu, Jian Zhang, Yiwen Li, Xiang Luo, Gang Zhou, Jie Xu, Fei Ren, Hong DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1 |
title | DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1 |
title_full | DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1 |
title_fullStr | DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1 |
title_full_unstemmed | DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1 |
title_short | DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1 |
title_sort | dicer1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin d1 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459849/ https://www.ncbi.nlm.nih.gov/pubmed/25702703 http://dx.doi.org/10.1111/jcmm.12522 |
work_keys_str_mv | AT sunxin dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT tangshouching dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT xuchongwen dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT wangchenguang dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT qinsida dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT duning dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT liujian dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT zhangyiwen dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT lixiang dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT luogang dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT zhoujie dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT xufei dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 AT renhong dicer1regulatedlet7expressionlevelsinp53inducedcancerrepressionrequirescyclind1 |