Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2022; 28(4): 464-478
Published online Jan 28, 2022. doi: 10.3748/wjg.v28.i4.464
Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway
Dong-Xin Hu, Qi-Feng Sun, Lin Xu, Hong-Da Lu, Fan Zhang, Zhen-Miao Li, Ming-Yan Zhang
Dong-Xin Hu, Qi-Feng Sun, Lin Xu, Hong-Da Lu, Fan Zhang, Zhen-Miao Li, Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong Province, China
Ming-Yan Zhang, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong Province, China
Author contributions: Hu DX, Sun QF, Xu L, Li ZM, Lu HD, and Zhang F contributed to the material preparation, data collection and analyses; Hu DX and Zhang MY contributed to the first draft; All authors contributed to the study conception and design, commented on previous versions of the manuscript, and read and approved the final manuscript.
Supported by the Natural Science Foundation of Shandong Province, No. ZR2020QH194.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University.
Institutional animal care and use committee statement: All animal experiments were approved with Shandong Provincial Hospital Affiliated to Shandong First Medical University.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Yan Zhang, MD, Associate Chief Physician, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwuwei Seventh Road, Huaiyin District, Jinan 250000, Shandong Province, China. zhangmingyan@sdfmu.edu.cn
Received: August 8, 2021
Peer-review started: August 8, 2021
First decision: November 7, 2021
Revised: November 15, 2021
Accepted: January 6, 2022
Article in press: January 6, 2022
Published online: January 28, 2022
Processing time: 166 Days and 22.7 Hours
ARTICLE HIGHLIGHTS
Research background

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies that seriously threatens people’s health worldwide. DDX51 is a member of the DEAD-box (DDX) RNA helicase family, which drives or inhibits tumor progression in multiple cancer types.

Research motivation

To identify the role of DDX51 in ESCC and the molecular mechanisms involved.

Research objectives

To explore the effect of DDX51 on ESCC progression.

Research methods

The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by immunohistochemistry analysis and quantitative PCR (qPCR). We knocked down DDX51 in ESCC cell lines using small interfering RNA (siRNA) transfection. The proliferation, apoptosis, and mobility of DDX51 siRNA-transfected cells were detected. The effects of DDX51 on the phosphoinositide 3-kinase (PI3K)/AKT pathway were investigated using western blot analysis. A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.

Research results

DDX51 exhibited high expression in ESCC tissues compared with normal tissues and was associated with a poor prognosis in patients with ESCC. Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis. Moreover, DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates. Investigation into the mechanism of action suggested that DDX51 knockdown induced inactivation of the PI3K/AKT pathway including decreased phosphorylation levels of PTEN, PI3K, AKT and mTOR. Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development. Finally, we injected DDX51 siRNA transfected TE-1 cell into an animal model, which resulted in slower tumor growth.

Research conclusions

Our study suggests for the first time that DDX51 contributes to ESCC cell proliferation by regulating the PI3K/AKT signaling pathway.

Research perspectives

DDX51 may serve as a potential therapeutic target for the treatment of ESCC.