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HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation

Human hedgehog-interacting protein (HHIP), a negative regulator of hedgehog (HH) signaling pathway, has been reported to be dysregulated in many types of cancer, including gastric cancer. However, the inhibitory role of HHIP as well as the underlying molecular mechanism of HHIP regulation in gastric...

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Autores principales: Song, Yu, Tu, Jianchen, Cheng, Yanan, Zhou, Fang, Liu, Peilin, Zhou, Shuangshuang, Gu, Yongjun, Sun, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784629/
https://www.ncbi.nlm.nih.gov/pubmed/33415068
http://dx.doi.org/10.3389/fonc.2020.01667
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author Song, Yu
Tu, Jianchen
Cheng, Yanan
Zhou, Fang
Liu, Peilin
Zhou, Shuangshuang
Gu, Yongjun
Sun, Yang
author_facet Song, Yu
Tu, Jianchen
Cheng, Yanan
Zhou, Fang
Liu, Peilin
Zhou, Shuangshuang
Gu, Yongjun
Sun, Yang
author_sort Song, Yu
collection PubMed
description Human hedgehog-interacting protein (HHIP), a negative regulator of hedgehog (HH) signaling pathway, has been reported to be dysregulated in many types of cancer, including gastric cancer. However, the inhibitory role of HHIP as well as the underlying molecular mechanism of HHIP regulation in gastric cancer haven’t been fully elucidated yet. In this study, we demonstrated that HHIP overexpression significantly suppressed the proliferation and invasion of AGS cells evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays, respectively. Interestingly, methylation-specific polymerase chain reaction (MS-PCR, MSP) showed that HHIP overexpression dramatically decreased its de novo promoter methylation levels in AGS cells. Furthermore, HHIP expression was higher in adjacent non-cancerous tissue compared to matched gastric cancer tissue. High HHIP level was negatively correlated with metastasis (p = 0.035) but not local recurrence (p = 0.58). Taken together, our study suggested that HHIP can modulate gastric cancer progression and metastasis via regulation of its de novo promoter methylation levels in a feedback manner. Lower HHIP levels is positively associated with gastric cancer metastasis, which not only indicates HHIP could be served as a protective marker for gastric cancer, but also suggests restoring HHIP expression might be a potential therapeutic strategy for clinical treatment.
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spelling pubmed-77846292021-01-06 HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation Song, Yu Tu, Jianchen Cheng, Yanan Zhou, Fang Liu, Peilin Zhou, Shuangshuang Gu, Yongjun Sun, Yang Front Oncol Oncology Human hedgehog-interacting protein (HHIP), a negative regulator of hedgehog (HH) signaling pathway, has been reported to be dysregulated in many types of cancer, including gastric cancer. However, the inhibitory role of HHIP as well as the underlying molecular mechanism of HHIP regulation in gastric cancer haven’t been fully elucidated yet. In this study, we demonstrated that HHIP overexpression significantly suppressed the proliferation and invasion of AGS cells evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays, respectively. Interestingly, methylation-specific polymerase chain reaction (MS-PCR, MSP) showed that HHIP overexpression dramatically decreased its de novo promoter methylation levels in AGS cells. Furthermore, HHIP expression was higher in adjacent non-cancerous tissue compared to matched gastric cancer tissue. High HHIP level was negatively correlated with metastasis (p = 0.035) but not local recurrence (p = 0.58). Taken together, our study suggested that HHIP can modulate gastric cancer progression and metastasis via regulation of its de novo promoter methylation levels in a feedback manner. Lower HHIP levels is positively associated with gastric cancer metastasis, which not only indicates HHIP could be served as a protective marker for gastric cancer, but also suggests restoring HHIP expression might be a potential therapeutic strategy for clinical treatment. Frontiers Media S.A. 2020-12-22 /pmc/articles/PMC7784629/ /pubmed/33415068 http://dx.doi.org/10.3389/fonc.2020.01667 Text en Copyright © 2020 Song, Tu, Cheng, Zhou, Liu, Zhou, Gu and Sun. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Song, Yu
Tu, Jianchen
Cheng, Yanan
Zhou, Fang
Liu, Peilin
Zhou, Shuangshuang
Gu, Yongjun
Sun, Yang
HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation
title HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation
title_full HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation
title_fullStr HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation
title_full_unstemmed HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation
title_short HHIP Overexpression Suppresses Human Gastric Cancer Progression and Metastasis by Reducing Its CpG Island Methylation
title_sort hhip overexpression suppresses human gastric cancer progression and metastasis by reducing its cpg island methylation
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784629/
https://www.ncbi.nlm.nih.gov/pubmed/33415068
http://dx.doi.org/10.3389/fonc.2020.01667
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