Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2019; 25(40): 6063-6076
Published online Oct 28, 2019. doi: 10.3748/wjg.v25.i40.6063
Insulin-like growth factor 2 mRNA-binding protein 1 promotes cell proliferation via activation of AKT and is directly targeted by microRNA-494 in pancreatic cancer
Bai-Shun Wan, Ming Cheng, Ling Zhang
Bai-Shun Wan, Ling Zhang, Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan Province, China
Ming Cheng, Department of Information, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
Author contributions: Wan BS and Zhang L designed the research and critically revised the manuscript for important intellectual content; Cheng M helped with the statistical analysis; all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 61802350.
Institutional review board statement: This study was approved by the Institutional Review Board of the Affiliated Cancer Hospital of Zhengzhou University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Affiliated Cancer Hospital of Zhengzhou University.
Conflict-of-interest statement: All authors declare no competing financial interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This 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: Ling Zhang, MD, Professor, Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Cancer Hospital of Zhengzhou University, No. 127, Dongming Road, Zhengzhou 450008, Henan Province, China. zzuzhangling@163.com
Telephone: +86-371-65587787 Fax: +86-371-65587787
Received: July 13, 2019
Peer-review started: July 16, 2019
First decision: August 18, 2019
Revised: September 3, 2019
Accepted: September 27, 2019
Article in press: September 28, 2019
Published online: October 28, 2019
Abstract
BACKGROUND

Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays critical roles in the genesis and development of human cancers.

AIM

To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.

METHODS

Expression levels of IGF2BP1 and microRNA-494 (miR-494) were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot. The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed. The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo. Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the post-transcriptional regulation of IGF2BP1 by miR-494.

RESULTS

We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients. We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway. Mechanistically, we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer. Furthermore, we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.

CONCLUSION

Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.

Keywords: Pancreatic cancer, Insulin-like growth factor 2 mRNA-binding protein 1, Proliferation, MicroRNA-494

Core tip: Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) exerts vital roles in the development of various cancers; however, the expression, functional role, and regulatory mechanisms of IGF2BP1 in pancreatic cancer remain unclear. In this study, the expression levels of IGF2BP1 and miR-494 were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines. The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed. The effect of IGF2BP1 on pancreatic cancer cell proliferation and underlying regulatory mechanism were investigated. Our study suggests that IGF2BP1 may be a new therapeutic target for pancreatic cancer.