Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2019; 25(22): 2776-2787
Published online Jun 14, 2019. doi: 10.3748/wjg.v25.i22.2776
Sp1 contributes to overexpression of stanniocalcin 2 through regulation of promoter activity in colon adenocarcinoma
Ji-Bin Li, Zhe-Xian Liu, Rui Zhang, Si-Ping Ma, Tao Lin, Yan-Xi Li, Shi-Hua Yang, Wan-Chuan Zhang, Yong-Peng Wang
Ji-Bin Li, Zhe-Xian Liu, Rui Zhang, Si-Ping Ma, Tao Lin, Yan-Xi Li, Shi-Hua Yang, Wan-Chuan Zhang, Yong-Peng Wang, Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, China
Shi-Hua Yang, Wan-Chuan Zhang, China Medical University, Shenyang 110000, Liaoning Province, China
Author contributions: Li JB and Liu ZX contributed equally to this study; Li JB, Liu ZX, Zhang R, Ma SP, Lin T, and Li YX conducted the experiments and data analysis.; Yang SH and Zhang WC provided technical support and participated in the project discussion; Yang SH and Liu ZX drafted the manuscript; Li JB, Zhang R, and Wang YP designed and directed the project; All authors read and approved the submission of the manuscript.
Supported by: the Natural Science Foundation of Liaoning Province, China, No. 20180550769.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yong-Peng Wang, MD, Director, Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, NO. 44, Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China. zzzrrr1234@sina.com
Telephone: +86-24-24315679 Fax: +86-24-24315679
Received: March 27, 2019
Peer-review started: March 27, 2019
First decision: April 17, 2019
Revised: April 22, 2019
Accepted: April 29, 2019
Article in press: April 29, 2019
Published online: June 14, 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.

Keywords: Transcription factor Sp1, Stanniocalcin 2, Overexpression, Promoter activity, Colon adenocarcinoma

Core tip: This study demonstrated that stanniocalcin 2 (STC2) is overexpressed in colon adenocarcinoma (COAD) and that high expression of STC2 predicts poor prognosis. The promoter of STC2 in COAD was hypermethylated, and the transcription factor Sp1 was essential for STC2 expression. These findings provide new insights into the mechanism of oncogenic function of STC2 in COAD.