The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation

BACKGROUND: The aim of this study is to explore the molecular mechanism of the LIM protein Ajuba and the transcription factor SP1 in the pathogenesis and progression of PDAC. Ajuba is a newly defined transcriptional co-regulator and plays important role in various cancer development, while SP1 is a...

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Autores principales: Zhang, Bosen, Song, Liwei, Cai, Jiali, Li, Lei, Xu, Hong, Li, Mengying, Wang, Jiamin, Shi, Minmin, Chen, Hao, Jia, Hao, Hou, Zhaoyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525466/
https://www.ncbi.nlm.nih.gov/pubmed/31101117
http://dx.doi.org/10.1186/s13046-019-1203-2
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author Zhang, Bosen
Song, Liwei
Cai, Jiali
Li, Lei
Xu, Hong
Li, Mengying
Wang, Jiamin
Shi, Minmin
Chen, Hao
Jia, Hao
Hou, Zhaoyuan
author_facet Zhang, Bosen
Song, Liwei
Cai, Jiali
Li, Lei
Xu, Hong
Li, Mengying
Wang, Jiamin
Shi, Minmin
Chen, Hao
Jia, Hao
Hou, Zhaoyuan
author_sort Zhang, Bosen
collection PubMed
description BACKGROUND: The aim of this study is to explore the molecular mechanism of the LIM protein Ajuba and the transcription factor SP1 in the pathogenesis and progression of PDAC. Ajuba is a newly defined transcriptional co-regulator and plays important role in various cancer development, while SP1 is a classic transcription factor, and is closely related with a variety of gene expression and cancer development including PDAC. METHODS: The expression of Ajuba and SP1 in PDAC tissues was detected by immunohistochemistry (IHC), and the correlation between expression level and clinical prognosis of Ajuba and SP1 was extensively analyzed using online tools. The interaction between Ajuba and SP1 was examined by co-immunoprecipitation (co-IP) and GST-pulldown assays. Stable cell lines were established via lentiviral infection, and was examined by qRT-PCR and western blot assays. The effects of Ajuba/SP1 on PDAC cell proliferation were examined using CCK8 and colony formation assays. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were employed to examine the transcription activity. RESULTS: The expression level (protein and mRNA) of Ajuba and SP1 was elevated in PDAC tissues and was positively correlated; patients with high Ajuba and SP1 expression had a poor prognosis. Mechanistically, Ajuba binds to the C-terminus of SP1 and functions as a co-activator to enhance SP1 gene expression and promote cell proliferation; the promoter of Ajuba contains functional SP1 responsive elements and Ajuba itself is a target gene of SP1. CONCLUSION: Ajuba functions as a co-activator of SP1 to induce its target gene, and that Ajuba itself is a target genes of SP1. Ajuba/SP1 complex could form a feed forward loop to drive SP1 target gene transcription and promote cell proliferation of pancreatic cancer cells. Ajuba and SP1 might be biomarkers for PDAC diagnostics, prognosis and targets for new therapeutics.
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spelling pubmed-65254662019-05-24 The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation Zhang, Bosen Song, Liwei Cai, Jiali Li, Lei Xu, Hong Li, Mengying Wang, Jiamin Shi, Minmin Chen, Hao Jia, Hao Hou, Zhaoyuan J Exp Clin Cancer Res Research BACKGROUND: The aim of this study is to explore the molecular mechanism of the LIM protein Ajuba and the transcription factor SP1 in the pathogenesis and progression of PDAC. Ajuba is a newly defined transcriptional co-regulator and plays important role in various cancer development, while SP1 is a classic transcription factor, and is closely related with a variety of gene expression and cancer development including PDAC. METHODS: The expression of Ajuba and SP1 in PDAC tissues was detected by immunohistochemistry (IHC), and the correlation between expression level and clinical prognosis of Ajuba and SP1 was extensively analyzed using online tools. The interaction between Ajuba and SP1 was examined by co-immunoprecipitation (co-IP) and GST-pulldown assays. Stable cell lines were established via lentiviral infection, and was examined by qRT-PCR and western blot assays. The effects of Ajuba/SP1 on PDAC cell proliferation were examined using CCK8 and colony formation assays. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were employed to examine the transcription activity. RESULTS: The expression level (protein and mRNA) of Ajuba and SP1 was elevated in PDAC tissues and was positively correlated; patients with high Ajuba and SP1 expression had a poor prognosis. Mechanistically, Ajuba binds to the C-terminus of SP1 and functions as a co-activator to enhance SP1 gene expression and promote cell proliferation; the promoter of Ajuba contains functional SP1 responsive elements and Ajuba itself is a target gene of SP1. CONCLUSION: Ajuba functions as a co-activator of SP1 to induce its target gene, and that Ajuba itself is a target genes of SP1. Ajuba/SP1 complex could form a feed forward loop to drive SP1 target gene transcription and promote cell proliferation of pancreatic cancer cells. Ajuba and SP1 might be biomarkers for PDAC diagnostics, prognosis and targets for new therapeutics. BioMed Central 2019-05-17 /pmc/articles/PMC6525466/ /pubmed/31101117 http://dx.doi.org/10.1186/s13046-019-1203-2 Text en © The Author(s). 2019 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
Zhang, Bosen
Song, Liwei
Cai, Jiali
Li, Lei
Xu, Hong
Li, Mengying
Wang, Jiamin
Shi, Minmin
Chen, Hao
Jia, Hao
Hou, Zhaoyuan
The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
title The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
title_full The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
title_fullStr The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
title_full_unstemmed The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
title_short The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
title_sort lim protein ajuba/sp1 complex forms a feed forward loop to induce sp1 target genes and promote pancreatic cancer cell proliferation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525466/
https://www.ncbi.nlm.nih.gov/pubmed/31101117
http://dx.doi.org/10.1186/s13046-019-1203-2
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