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Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells

Ghrelin, an orexigenic peptide, acts via the growth hormone secretagogue receptor (GHSR) to stimulate the release of growth hormone. Moreover, it has a range of biological actions, including the stimulation of food intake, modulation of insulin signaling and cardiovascular effects. Recently, it has...

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Autores principales: Liu, An, Huang, Chenggang, Xu, Jia, Cai, Xuehong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055151/
https://www.ncbi.nlm.nih.gov/pubmed/27464938
http://dx.doi.org/10.1002/cam4.723
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author Liu, An
Huang, Chenggang
Xu, Jia
Cai, Xuehong
author_facet Liu, An
Huang, Chenggang
Xu, Jia
Cai, Xuehong
author_sort Liu, An
collection PubMed
description Ghrelin, an orexigenic peptide, acts via the growth hormone secretagogue receptor (GHSR) to stimulate the release of growth hormone. Moreover, it has a range of biological actions, including the stimulation of food intake, modulation of insulin signaling and cardiovascular effects. Recently, it has been demonstrated that ghrelin has a proliferative and antiapoptotic effects in cancers, suggesting a potential role in promoting tumor growth. However, it remains unknown whether GHSR contributes to colorectal cancer proliferation. In this study, the therapeutic effect of lentivirus‐mediated short hairpin RNA (shRNA) targeting ghrelin receptor 1a (GHSR1a) was analyzed in colorectal cancer cell line SW480 both in vitro and in vivo. Our study demonstrated that ghrelin and GHSR1a are significantly upregulated in cancerous colorectal tissue samples and cell lines. In vitro, human colorectal cancer cell line SW480 with downregulation of GHSR1a by shRNA showed significant inhibition of cell viability compared with blank control (BC) or scrambled control (SC) regardless of the application of exogenous ghrelin. Furthermore, GHSR1a silencing by target specific shRNA was shown capable of increasing PTEN, inhibiting AKT phosphorylation and promoting the release of p53 in SW480 cells. In addition, the effects of GHSR1a knockdown were further explored in vivo using colorectal tumor xenograft mouse model. The tumor weights were decreased markedly in GHSR1α knockdown SW480 mouse xenograft tumors compared with blank control or negative control tumors. Our results suggested that the expression of GHSR1a is significantly correlated with the growth of colorectal cancer cells, and the GHSR1a knockdown approach may be a potential therapy for the treatment of colorectal cancer.
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spelling pubmed-50551512016-12-12 Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells Liu, An Huang, Chenggang Xu, Jia Cai, Xuehong Cancer Med Cancer Biology Ghrelin, an orexigenic peptide, acts via the growth hormone secretagogue receptor (GHSR) to stimulate the release of growth hormone. Moreover, it has a range of biological actions, including the stimulation of food intake, modulation of insulin signaling and cardiovascular effects. Recently, it has been demonstrated that ghrelin has a proliferative and antiapoptotic effects in cancers, suggesting a potential role in promoting tumor growth. However, it remains unknown whether GHSR contributes to colorectal cancer proliferation. In this study, the therapeutic effect of lentivirus‐mediated short hairpin RNA (shRNA) targeting ghrelin receptor 1a (GHSR1a) was analyzed in colorectal cancer cell line SW480 both in vitro and in vivo. Our study demonstrated that ghrelin and GHSR1a are significantly upregulated in cancerous colorectal tissue samples and cell lines. In vitro, human colorectal cancer cell line SW480 with downregulation of GHSR1a by shRNA showed significant inhibition of cell viability compared with blank control (BC) or scrambled control (SC) regardless of the application of exogenous ghrelin. Furthermore, GHSR1a silencing by target specific shRNA was shown capable of increasing PTEN, inhibiting AKT phosphorylation and promoting the release of p53 in SW480 cells. In addition, the effects of GHSR1a knockdown were further explored in vivo using colorectal tumor xenograft mouse model. The tumor weights were decreased markedly in GHSR1α knockdown SW480 mouse xenograft tumors compared with blank control or negative control tumors. Our results suggested that the expression of GHSR1a is significantly correlated with the growth of colorectal cancer cells, and the GHSR1a knockdown approach may be a potential therapy for the treatment of colorectal cancer. John Wiley and Sons Inc. 2016-07-27 /pmc/articles/PMC5055151/ /pubmed/27464938 http://dx.doi.org/10.1002/cam4.723 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (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 Cancer Biology
Liu, An
Huang, Chenggang
Xu, Jia
Cai, Xuehong
Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells
title Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells
title_full Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells
title_fullStr Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells
title_full_unstemmed Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells
title_short Lentivirus‐mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells
title_sort lentivirus‐mediated shrna interference of ghrelin receptor blocks proliferation in the colorectal cancer cells
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055151/
https://www.ncbi.nlm.nih.gov/pubmed/27464938
http://dx.doi.org/10.1002/cam4.723
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