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.
基金：
National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31671415, 31601114, 81402177]; Shanghai talent development funding [2017034]; Shanghai Rising-Star Program [19QA1405000]
第一作者机构：[1]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Surg, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China[2]Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Hongqiao Int Inst Med,Fac Basic Med, 280 South Chongqing Rd, Shanghai 200025, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[2]Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Hongqiao Int Inst Med,Fac Basic Med, 280 South Chongqing Rd, Shanghai 200025, Peoples R China[5]Lanling Peoples Hosp, Dept Thorac Surg, Linyi 277700, Shandong, Peoples R China[6]Shanghai Jiao Tong Univ, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Dept Biochem & Mol Cell Biol, 280 South Chongqing Rd, Shanghai 200025, Peoples R China
推荐引用方式(GB/T 7714)：
Zhang Bosen,Song Liwei,Cai Jiali,et al.The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2019,38:doi:10.1186/s13046-019-1203-2.
APA：
Zhang, Bosen,Song, Liwei,Cai, Jiali,Li, Lei,Xu, Hong...&Hou, Zhaoyuan.(2019).The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,38,
MLA：
Zhang, Bosen,et al."The LIM protein Ajuba/SP1 complex forms a feed forward loop to induce SP1 target genes and promote pancreatic cancer cell proliferation".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 38.(2019)
医学