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Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients

One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoti...

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Autores principales: Tsoi, H, Lam, K C, Dong, Y, Zhang, X, Lee, C K, Zhang, J, Ng, S C, Ng, S S M, Zheng, S, Chen, Y, Fang, J, Yu, J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671943/
https://www.ncbi.nlm.nih.gov/pubmed/28692053
http://dx.doi.org/10.1038/onc.2017.86
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author Tsoi, H
Lam, K C
Dong, Y
Zhang, X
Lee, C K
Zhang, J
Ng, S C
Ng, S S M
Zheng, S
Chen, Y
Fang, J
Yu, J
author_facet Tsoi, H
Lam, K C
Dong, Y
Zhang, X
Lee, C K
Zhang, J
Ng, S C
Ng, S S M
Zheng, S
Chen, Y
Fang, J
Yu, J
author_sort Tsoi, H
collection PubMed
description One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.
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spelling pubmed-56719432017-11-09 Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients Tsoi, H Lam, K C Dong, Y Zhang, X Lee, C K Zhang, J Ng, S C Ng, S S M Zheng, S Chen, Y Fang, J Yu, J Oncogene Original Article One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients. Nature Publishing Group 2017-11-02 2017-07-10 /pmc/articles/PMC5671943/ /pubmed/28692053 http://dx.doi.org/10.1038/onc.2017.86 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
Tsoi, H
Lam, K C
Dong, Y
Zhang, X
Lee, C K
Zhang, J
Ng, S C
Ng, S S M
Zheng, S
Chen, Y
Fang, J
Yu, J
Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
title Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
title_full Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
title_fullStr Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
title_full_unstemmed Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
title_short Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients
title_sort pre-45s rrna promotes colon cancer and is associated with poor survival of crc patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671943/
https://www.ncbi.nlm.nih.gov/pubmed/28692053
http://dx.doi.org/10.1038/onc.2017.86
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