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NF-κB potentiates tumor growth by suppressing a novel target LPTS
BACKGROUND: Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incomplet...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634951/ https://www.ncbi.nlm.nih.gov/pubmed/29017500 http://dx.doi.org/10.1186/s12964-017-0196-8 |
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author | Liu, Dongbo Miao, Hongping Zhao, Yuanyin Kang, Xia Shang, Shenglan Xiang, Wei Shi, Rongchen Hou, Along Wang, Rui Zhao, Kun Liu, Yingzhe Ma, Yue Luo, Huan Miao, Hongming He, Fengtian |
author_facet | Liu, Dongbo Miao, Hongping Zhao, Yuanyin Kang, Xia Shang, Shenglan Xiang, Wei Shi, Rongchen Hou, Along Wang, Rui Zhao, Kun Liu, Yingzhe Ma, Yue Luo, Huan Miao, Hongming He, Fengtian |
author_sort | Liu, Dongbo |
collection | PubMed |
description | BACKGROUND: Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated. METHODS: Real-time PCR and western blotting were used to determine the expression of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation were performed to decipher the regulatory mechanism between p65 and LPTS. Cell counting kit-8 assays and xenograt models were used to detect p65-LPTS-regulated cancer cell growth in vitro and in vivo, respectively. RESULTS: Here we for the first time demonstrated that NF-κB could inhibit LPTS expression in the mRNA and protein levels in multiple cancer cells (e.g. cervical cancer and colon cancer cells). Mechanistically, NF-κB p65 could bind to two consensus response elements locating at −1143/−1136 and −888/−881 in the promoter region of human LPTS gene according to EMSA and ChIP assays. Mutation of those two binding sites rescued p65-suppressed LPTS promoter activity. Functionally, NF-κB regulated LPTS-dependent cell growth of cervical and colon cancers in vitro and in xenograft models. In translation studies, we verified that increased p65 expression was associated with decreased LPTS level in multiple solid cancers. CONCLUSIONS: Taken together, we revealed that NF-κB p65 potentiated tumor growth via suppressing a novel target LPTS. Modulation of NF-κB-LPTS axis represented a potential strategy for treatment of those inflammation-associated malignancies. |
format | Online Article Text |
id | pubmed-5634951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-56349512017-10-19 NF-κB potentiates tumor growth by suppressing a novel target LPTS Liu, Dongbo Miao, Hongping Zhao, Yuanyin Kang, Xia Shang, Shenglan Xiang, Wei Shi, Rongchen Hou, Along Wang, Rui Zhao, Kun Liu, Yingzhe Ma, Yue Luo, Huan Miao, Hongming He, Fengtian Cell Commun Signal Research BACKGROUND: Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated. METHODS: Real-time PCR and western blotting were used to determine the expression of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation were performed to decipher the regulatory mechanism between p65 and LPTS. Cell counting kit-8 assays and xenograt models were used to detect p65-LPTS-regulated cancer cell growth in vitro and in vivo, respectively. RESULTS: Here we for the first time demonstrated that NF-κB could inhibit LPTS expression in the mRNA and protein levels in multiple cancer cells (e.g. cervical cancer and colon cancer cells). Mechanistically, NF-κB p65 could bind to two consensus response elements locating at −1143/−1136 and −888/−881 in the promoter region of human LPTS gene according to EMSA and ChIP assays. Mutation of those two binding sites rescued p65-suppressed LPTS promoter activity. Functionally, NF-κB regulated LPTS-dependent cell growth of cervical and colon cancers in vitro and in xenograft models. In translation studies, we verified that increased p65 expression was associated with decreased LPTS level in multiple solid cancers. CONCLUSIONS: Taken together, we revealed that NF-κB p65 potentiated tumor growth via suppressing a novel target LPTS. Modulation of NF-κB-LPTS axis represented a potential strategy for treatment of those inflammation-associated malignancies. BioMed Central 2017-10-10 /pmc/articles/PMC5634951/ /pubmed/29017500 http://dx.doi.org/10.1186/s12964-017-0196-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Liu, Dongbo Miao, Hongping Zhao, Yuanyin Kang, Xia Shang, Shenglan Xiang, Wei Shi, Rongchen Hou, Along Wang, Rui Zhao, Kun Liu, Yingzhe Ma, Yue Luo, Huan Miao, Hongming He, Fengtian NF-κB potentiates tumor growth by suppressing a novel target LPTS |
title | NF-κB potentiates tumor growth by suppressing a novel target LPTS |
title_full | NF-κB potentiates tumor growth by suppressing a novel target LPTS |
title_fullStr | NF-κB potentiates tumor growth by suppressing a novel target LPTS |
title_full_unstemmed | NF-κB potentiates tumor growth by suppressing a novel target LPTS |
title_short | NF-κB potentiates tumor growth by suppressing a novel target LPTS |
title_sort | nf-κb potentiates tumor growth by suppressing a novel target lpts |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634951/ https://www.ncbi.nlm.nih.gov/pubmed/29017500 http://dx.doi.org/10.1186/s12964-017-0196-8 |
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