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
ARTICLE HIGHLIGHTS
Research background

Pancreatic cancer is one of the most common causes of cancer-related deaths worldwide. Current treatment options for patients with pancreatic cancer are very limited, and the clinical outcomes remain unsatisfactory. New therapy targets are necessary to improve the survival rates of pancreatic cancer patients. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays critical roles in the genesis and development of human cancers. Little is known regarding IGF2BP1 expression and its role in the carcinogenesis or progression of pancreatic ductal adenocarcinoma (PDAC).

Research motivation

Our findings will provide a new therapeutic target for pancreatic cancer.

Research objectives

To study the expression, function, and regulatory mechanisms of IGF2BP1 in pancreatic cancer.

Research methods

We detected the expression levels of IGF2BP1 and miR-494 in Gene Expression Omnibus datasets and validated in clinical samples 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.

Research results

In the present study, we found that IGF2BP1 was upregulated and associated with a poor prognosis of pancreatic cancer patients. We showed that knockdown of IGF2BP1 reduced pancreatic cancer cell proliferation in vitro and in vivo via the AKT signaling pathway. Meanwhile, the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.

Research conclusions

IGF2BP1 is upregulated and promotes the proliferation of pancreatic cancer via the AKT signaling pathway. Upregulation of IGF2BP1 is partly due to the silencing of miR-494.

Research perspectives

This study provides insight into the role of IGF2BP1 in promoting pancreatic cancer development by activating AKT. IGF2BP1 might be a new therapeutic target for pancreatic cancer.