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
Abstract
BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies that seriously threaten people’s health worldwide. DEAD-box helicase 51 (DDX51) is a member of the DEAD-box (DDX) RNA helicase family, and drives or inhibits tumor progression in multiple cancer types.

AIM

To determine whether DDX51 affects the biological behavior of ESCC.

METHODS

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

RESULTS

DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented 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. Investigations into the underlying mechanisms suggested that DDX51 knockdown induced inactivation of the PI3K/AKT pathway, including decreased phosphorylation levels of phosphate and tensin homolog, PI3K, AKT, and mammalian target of rapamycin. 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 cells into an animal model, which resulted in slower tumor growth.

CONCLUSION

Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway; thus, DDX51 might be a therapeutic target for ESCC.

Keywords: Esophageal squamous cell carcinoma; DDX51; PI3K/AKT pathway; Tumor growth; Therapeutic target

Core Tip: Our study revealed that DEAD-box helicase 51 was upregulated in esophageal squamous cell carcinoma (ESCC) tumor tissues and promoted tumor proliferation and development by upregulating the phosphorylation of phosphoinositide 3-kinase/AKT pathway members. These data extend our knowledge of the function and molecular mechanism of the DEAD-box family in tumor biology and provide a potential therapeutic target for ESCC treatment.