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Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer

Rho GDP‐dissociation inhibitor α (RhoGDIα) is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We...

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Autores principales: Huang, Dandan, Lu, Weisi, Zou, Shaomin, Wang, Huaiming, Jiang, Yuanling, Zhang, Xiya, Li, Pengqing, Songyang, Zhou, Wang, Lei, Wang, Jianping, Huang, Junjiu, Fang, Lekun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497806/
https://www.ncbi.nlm.nih.gov/pubmed/28417530
http://dx.doi.org/10.1111/cas.13259
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author Huang, Dandan
Lu, Weisi
Zou, Shaomin
Wang, Huaiming
Jiang, Yuanling
Zhang, Xiya
Li, Pengqing
Songyang, Zhou
Wang, Lei
Wang, Jianping
Huang, Junjiu
Fang, Lekun
author_facet Huang, Dandan
Lu, Weisi
Zou, Shaomin
Wang, Huaiming
Jiang, Yuanling
Zhang, Xiya
Li, Pengqing
Songyang, Zhou
Wang, Lei
Wang, Jianping
Huang, Junjiu
Fang, Lekun
author_sort Huang, Dandan
collection PubMed
description Rho GDP‐dissociation inhibitor α (RhoGDIα) is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We founded that downregulation of RhoGDIα repressed CRC cell proliferation, motility, and invasion. Overexpression of RhoGDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that RhoGDIα could promote telomeric repeat factor 1 (TRF1) expression through the phosphatidylinositol 3‐kinase–protein kinase B signal pathway. Moreover, RhoGDIα protein levels were strongly correlated with TRF1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between RhoGDIα and TRF1, and revealed that RhoGDIα and TRF1 levels were negatively associated with CRC patients' survival. Taken together, our results suggest that RhoGDIα regulate TRF1 and telomere length and may be novel prognostic biomarkers in colorectal cancer.
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spelling pubmed-54978062017-07-10 Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer Huang, Dandan Lu, Weisi Zou, Shaomin Wang, Huaiming Jiang, Yuanling Zhang, Xiya Li, Pengqing Songyang, Zhou Wang, Lei Wang, Jianping Huang, Junjiu Fang, Lekun Cancer Sci Original Articles Rho GDP‐dissociation inhibitor α (RhoGDIα) is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We founded that downregulation of RhoGDIα repressed CRC cell proliferation, motility, and invasion. Overexpression of RhoGDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that RhoGDIα could promote telomeric repeat factor 1 (TRF1) expression through the phosphatidylinositol 3‐kinase–protein kinase B signal pathway. Moreover, RhoGDIα protein levels were strongly correlated with TRF1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between RhoGDIα and TRF1, and revealed that RhoGDIα and TRF1 levels were negatively associated with CRC patients' survival. Taken together, our results suggest that RhoGDIα regulate TRF1 and telomere length and may be novel prognostic biomarkers in colorectal cancer. John Wiley and Sons Inc. 2017-05-31 2017-07 /pmc/articles/PMC5497806/ /pubmed/28417530 http://dx.doi.org/10.1111/cas.13259 Text en © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Huang, Dandan
Lu, Weisi
Zou, Shaomin
Wang, Huaiming
Jiang, Yuanling
Zhang, Xiya
Li, Pengqing
Songyang, Zhou
Wang, Lei
Wang, Jianping
Huang, Junjiu
Fang, Lekun
Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
title Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
title_full Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
title_fullStr Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
title_full_unstemmed Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
title_short Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
title_sort rho gdp‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497806/
https://www.ncbi.nlm.nih.gov/pubmed/28417530
http://dx.doi.org/10.1111/cas.13259
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