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Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Thus, identification of the mechanisms involved in the progression of CRC has become a crucial element of facilitating early CRC diagnosis and targeted therapy for...

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Autores principales: Hou, Bin, Li, Wenhan, Li, Jianhui, Ma, Jia, Xia, Peng, Liu, Zhao, Zeng, Qingnuo, Zhang, Xin, Chang, Dongmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967159/
https://www.ncbi.nlm.nih.gov/pubmed/31894339
http://dx.doi.org/10.3892/or.2019.7442
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author Hou, Bin
Li, Wenhan
Li, Jianhui
Ma, Jia
Xia, Peng
Liu, Zhao
Zeng, Qingnuo
Zhang, Xin
Chang, Dongmin
author_facet Hou, Bin
Li, Wenhan
Li, Jianhui
Ma, Jia
Xia, Peng
Liu, Zhao
Zeng, Qingnuo
Zhang, Xin
Chang, Dongmin
author_sort Hou, Bin
collection PubMed
description Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Thus, identification of the mechanisms involved in the progression of CRC has become a crucial element of facilitating early CRC diagnosis and targeted therapy for patients with advanced CRC. Currently, Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a type of histidine phosphatase protein, has been confirmed as a tumor suppressor in hepatocellular carcinoma (HCC) and cervical cancer. However, the functions and molecular mechanisms underlying LHPP in CRC remain undefined. The present study revealed that dysregulation of LHPP was frequently observed in CRC tissues and was positively correlated with tumor severity and poor prognosis. Functional experiments demonstrated that overexpression of LHPP impeded CRC cell growth and proliferation in vitro, and was associated with a change in p53 expression and PI3K/AKT activity. In contrast, silencing of LHPP significantly promoted cell growth and proliferation by modulating the PI3K/AKT signaling pathway. Notably, the anti-CRC effects of LHPP were also observed in nude mouse in vivo experiments. Overall, the data obtained in the present study suggested that LHPP may be exploited as a diagnostic and prognostic candidate for patients with CRC.
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spelling pubmed-69671592020-01-31 Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway Hou, Bin Li, Wenhan Li, Jianhui Ma, Jia Xia, Peng Liu, Zhao Zeng, Qingnuo Zhang, Xin Chang, Dongmin Oncol Rep Articles Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Thus, identification of the mechanisms involved in the progression of CRC has become a crucial element of facilitating early CRC diagnosis and targeted therapy for patients with advanced CRC. Currently, Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a type of histidine phosphatase protein, has been confirmed as a tumor suppressor in hepatocellular carcinoma (HCC) and cervical cancer. However, the functions and molecular mechanisms underlying LHPP in CRC remain undefined. The present study revealed that dysregulation of LHPP was frequently observed in CRC tissues and was positively correlated with tumor severity and poor prognosis. Functional experiments demonstrated that overexpression of LHPP impeded CRC cell growth and proliferation in vitro, and was associated with a change in p53 expression and PI3K/AKT activity. In contrast, silencing of LHPP significantly promoted cell growth and proliferation by modulating the PI3K/AKT signaling pathway. Notably, the anti-CRC effects of LHPP were also observed in nude mouse in vivo experiments. Overall, the data obtained in the present study suggested that LHPP may be exploited as a diagnostic and prognostic candidate for patients with CRC. D.A. Spandidos 2020-02 2019-12-20 /pmc/articles/PMC6967159/ /pubmed/31894339 http://dx.doi.org/10.3892/or.2019.7442 Text en Copyright: © Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Hou, Bin
Li, Wenhan
Li, Jianhui
Ma, Jia
Xia, Peng
Liu, Zhao
Zeng, Qingnuo
Zhang, Xin
Chang, Dongmin
Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway
title Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway
title_full Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway
title_fullStr Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway
title_full_unstemmed Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway
title_short Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway
title_sort tumor suppressor lhpp regulates the proliferation of colorectal cancer cells via the pi3k/akt pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967159/
https://www.ncbi.nlm.nih.gov/pubmed/31894339
http://dx.doi.org/10.3892/or.2019.7442
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