The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation
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LIM蛋白Ajuba/SP1复合物形成前馈环路诱导SP1靶基因并促进胰腺癌细胞增殖
DOI：
10.1186/s13046-019-1203-2
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发表时间：
2019-05
影响因子：
11.3
通讯作者：
Hou Zhaoyuan
中科院分区：
文献类型：
--
作者：
Zhang Bosen;Song Liwei;Cai Jiali;Li Lei;Xu Hong;Li Mengying;Wang Jiamin;Shi Minmin;Chen Hao;Jia Hao;Hou Zhaoyuan
BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionAjuba 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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影响因子：
5.3
作者：
Jagannathan R;Schimizzi GV;Zhang K;Loza AJ;Yabuta N;Nojima H;Longmore GD
通讯作者：
Longmore GD
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1146/annurev.pathol.3.121806.154305
发表时间：
2021-08
期刊：
Annual review of pathology
影响因子：
--
作者：
A. Maitra;R. Hruban
通讯作者：
A. Maitra;R. Hruban
Snail 招募 Ring1B 介导胰腺癌细胞的转录抑制和细胞迁移
影响因子：
11.2
作者：
Chen J;Xu H;Zou X;Wang J;Zhu Y;Chen H;Shen B;Deng X;Zhou A;Chin YE;Rauscher FJ 3rd;Peng C;Hou Z
通讯作者：
Hou Z
DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal