Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2020; 26(25): 3586-3602
Published online Jul 7, 2020. doi: 10.3748/wjg.v26.i25.3586
TBL1XR1 induces cell proliferation and inhibit cell apoptosis by the PI3K/AKT pathway in pancreatic ductal adenocarcinoma
Jian-Feng Gu, Wei Fu, Hai-Xin Qian, Wen-Xiu Gu, Yang Zong, Qian Chen, Long Lu
Jian-Feng Gu, Wen-Xiu Gu, Yang Zong, Qian Chen, Department of General Surgery, Changshu No. 1 People’s Hospital Affiliated to Soochow University, Changshu 215500, Jiangsu Province, China
Wei Fu, Long Lu, Department of Oncology, Changshu No. 1 People’s Hospital Affiliated to Soochow University, Changshu 215500, Jiangsu Province, China
Hai-Xin Qian, Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Author contributions: Gu JF and Fu W contributed equally to this work. Gu JF was involved in study concept and design, and acquisition, analysis and interpretation of data, drafted manuscript, critically revised the manuscript for important intellectual content, and provided statistical analysis and administrative, technical, or material support; Fu W performed data acquisition and drafted manuscript; Qian HX participated in data analysis and interpretation; Gu WX was involved in the drafting of the manuscript; Zong Y was involved in critically revising the manuscript for important intellectual content; Chen Q and Lu L took part in the statistical analysis.
Institutional animal care and use committee statement: The animal care and use was approved by the Ethics Committee of Changshu No.1 People’s Hospital.
Institutional review board statement: The study was approved by the Ethics Committee of Changshu No.1 People’s Hospital.
Conflict-of-interest statement: The authors declare no conflict of interest. The authors declare that they have nothing to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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 NonCommercial (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: Jian-Feng Gu, MD, Doctor, Department of General Surgery, Changshu No. 1 People’s Hospital Affiliated to Soochow University, No.91, Yongjia Road, Changshu 215500, Jiangsu Province, China. jscsgjf@sina.cn
Received: February 3, 2020
Peer-review started: February 3, 2020
First decision: March 24, 2020
Revised: March 26, 2020
Accepted: May 26, 2020
Article in press: May 26, 2020
Published online: July 7, 2020
Processing time: 155 Days and 4.1 Hours
Abstract
BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors. Identification of diagnostic and therapeutic biomarkers for PDAC is urgently needed. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been linked to the progression of various human cancers. Nevertheless, the function and role of TBL1XR1 in pancreatic cancers are unclear.

AIM

To elucidate the function and potential mechanism of TBL1XR1 in the development of PDAC.

METHODS

Ninety patients with histologically-confirmed PDAC were included in this study. PDAC tumor samples and cell lines were used to determine the expression of TBL1XR1. CCK-8 assays and colony formation assays were carried out to assess PDAC cell viability. Flow cytometry was performed to measure the changes in the cell cycle and cell apoptosis. Changes in related protein expression were measured by western blot analysis. Animal analysis was conducted to confirm the impact of TBL1XR1 in vivo.

RESULTS

Patients with TBL1XR1-positive tumors had worse overall survival than those with TBL1XR1-negative tumors. Moreover, we found that TBL1XR1 strongly promoted PDAC cell proliferation and inhibited PDAC cell apoptosis. Moreover, knockdown of TBL1XR1 induced G0/G1 phase arrest. In vivo animal studies confirmed that TBL1XR1 accelerated tumor cell growth. The results of western blot analysis showed that TBL1XR1 might play a key role in regulating PDAC cell proliferation and apoptosis via the PI3K/AKT pathway.

CONCLUSION

TBL1XR1 promoted PDAC cell progression and might be an effective diagnostic and therapeutic marker for pancreatic cancer.

Keywords: Pancreatic ductal adenocarcinoma; TBL1XR1; Proliferation; PI3K/AKT pathway

Core tip: Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been linked to the progression of various human cancers. However, the function and role of TBL1XR1 in pancreatic cancers are unclear. Elucidation of the effect and potential molecular mechanism of TBL1XR1 in pancreatic cancer is important. This study showed that TBL1XR1 promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation, inhibited PDAC cell apoptosis and might regulate PDAC cell proliferation and apoptosis by the phosphatidylinositol 3-kinase/protein kinase B pathway. Therefore, TBL1XR1 might be a promising therapeutic marker for patients with advanced PDAC.