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
Processing time: 79 Days and 5.9 Hours
ARTICLE HIGHLIGHTS
Research background

To date, growing evidence has shown that stanniocalcin 2 (STC2) might be a cancer-promoter in several cancer types. Some reports demonstrated that the expression of STC2 was higher in colon adenocarcinoma (COAD), but its significance needs further study as the effect of the overexpression of STC2 in COAD remains unclear.

Research motivation

COAD is an aggressive cancer and is linked with high mortality rate. A previous study demonstrated that STC2 might be an oncogenic factor in COAD. This study confirmed that STC2 is overexpressed in COAD and, for the first time, showed that transcription factor Sp1 was essential to the expression of STC2. These findings provide new insight into the oncogenic function of STC2 in COAD.

Research objectives

We confirmed the expression of STC2 and its clinical significance in COAD and evaluated the potential regulation mechanism for the overexpression of STC2.

Research methods

The expression of STC2 in COAD was confirmed with the TCGA database, and expression of STC2 in COAD with liver metastasis or not was confirmed by the GEO database. The methylation levels of the STC2 promoter was analyzed with the UALCAN tool. Survival of the high expression STC2 group and the low expression STC2 group was determined using the Kaplan Meier method. The pGL3 luciferase reporter system to analyze the activity of STC2 promoter. Western blotting was performed to identify the expression of STC2 in several cell lines and evaluate the effect of Sp1 on STC2 expression.

Research results

We confirmed that STC2 was overexpressed in COAD and that the expression of STC2 was positively correlated with the stage of COAD patients and liver metastasis, where high expression of STC2 predicted low survival. Interestingly, the promoter of STC2 was hypermethylated. Through construction of several luciferase reporter systems of STC2 to evaluate its promoter activity, we confirmed the core region of the STC2 promoter. Also, we evaluated if Sp1 was involved in the overexpression of STC2 in COAD.

Research conclusions

Our findings revealed for the first time that transcription factor Sp1 was essential to the overexpression of STC2 in the COAD. Sp1 mediated the expression of STC2 through regulation of its promoter activity. Furthermore, the promoter of STC2 was hypermethylation in COAD tumor tissues, suggesting that hypermethylation of the STC2 promoter might be another factor contributing to the overexpression of STC2. These data provide novel insight into the tumor-promoter function of STC2 in COAD.

Research perspectives

In this study, we showed that Sp1 contributed to the overexpression of STC2 in COAD and that the promoter of STC2 was hypermethylated. In the future, efforts should focus on the interaction between Sp1 and STC2 and the methylation of the promoter for the regulation of STC2.