摘要
BACKGROUND Aberrant expression of stanniocalcin 2(STC2)is implicated in colon adenocarcinoma(COAD).A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers,but the role of its overexpression in the development of COAD remains unclear.AIM To evaluate the regulation mechanism of STC2 overexpression in COAD.METHODS The expression of STC2 in COAD was assessed by TCGA COAD database and GEO(GSE50760).Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform,and the correlation between STC2 expression and survival rate was investigated with TCGA COAD.Transcription binding site prediction was conducted by TRANSFAC and LASAGNA,and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines,including HEK293T,NCM460,HT29,SW480,and HCT116.Western blotting was performed to evaluate the role of Sp1 on the expression of STC2.RESULTS The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis.Importantly,the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2.A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2,and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2.Furthermore,inhibition of Sp1 remarkably decreased protein levels of STC2.CONCLUSION Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity.Taken together,our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.
基金
the Natural Science Foundation of Liaoning Province,China,No.20180550769
