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Sp1 contributes to overexpression of stanniocalcin 2 through regulation of promoter activity in colon adenocarcinoma
- Source :
- World Journal of Gastroenterology
- Publication Year :
- 2019
- Publisher :
- Baishideng Publishing Group Inc, 2019.
-
Abstract
- 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.
- Subjects :
- Transcriptional Activation
Overexpression
Sp1 Transcription Factor
Biology
Adenocarcinoma
Promoter activity
Cell Line, Tumor
Stanniocalcin 2
Humans
Colon adenocarcinoma
Promoter Regions, Genetic
Glycoproteins
Sp1 transcription factor
Gastroenterology
General Medicine
Basic Study
DNA Methylation
Prognosis
digestive system diseases
Up-Regulation
Gene Expression Regulation, Neoplastic
Survival Rate
HEK293 Cells
Gene Knockdown Techniques
Colonic Neoplasms
Cancer research
Intercellular Signaling Peptides and Proteins
Transcription factor Sp1
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 22192840 and 10079327
- Volume :
- 25
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- World Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....505590d14386a490c770a8e61b2ca666