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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Y-box binding protein 1 augments sorafenib resistance via the PI3K/Akt signaling pathway in hepatocellular carcinoma
Ting Liu, Xiao-Li Xie, Xue Zhou, Sheng-Xiong Chen, Yi-Jun Wang, Lin-Ping Shi, Shu-Jia Chen, Yong-Juan Wang, Shu-Ling Wang, Jiu-Na Zhang, Shi-Ying Dou, Xiao-Yu Jiang, Ruo-Lin Cui, Hui-Qing Jiang
Ting Liu, Xiao-Li Xie, Xue Zhou, Yi-Jun Wang, Yong-Juan Wang, Shu-Ling Wang, Jiu-Na Zhang, Xiao-Yu Jiang, Ruo-Lin Cui, Hui-Qing Jiang, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Sheng-Xiong Chen, Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Lin-Ping Shi, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050000, Hebei Province, China
Shu-Jia Chen, Department of Gastroenterology, Shijiazhuang People’s Hospital, Shijiazhuang 050000, Hebei Province, China
Shi-Ying Dou, Department of Infectious Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Author contributions: Liu T, Xie XL and Jiang HQ conceived, designed the study; Liu T, Xie XL, Zhou X, Chen SX and Wang YJ performed most experiments, analyzed the data, wrote the manuscript and edited the paper; Xie XL and Jiang HQ helped to supervised the study; Shi LP, Chen SJ, Wang YJ, Wang SL, Zhang JN, Dou SY, Cui RL and Jiang XY helped to perform the experiments and analyzed the data; Xie XL and Jiang HQ helped to edited the paper.
Supported by National Natural Science Foundation of China, No. 81770601, No. 81702324, and No. 81602529; Natural Science Foundation of Hebei Province, No. H2018206176 and No. H2017206141; and Post-graduate’s Innovation Fund Project of Hebei Province, No. CXZZBS2019121.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Second Hospital of Hebei Medical University (approval letter No.: 2020-P025).
Institutional animal care and use committee statement: All animal procedures were approved by the ethics committee of the Second Hospital of Hebei Medical University (approval letter No.: 2020-AE002).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest in our study.
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: Hui-Qing Jiang, MD, Professor, Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China. jianghq@aliyun.com
Received: March 19, 2021
Peer-review started: March 19, 2021
First decision: June 3, 2021
Revised: June 4, 2021
Accepted: June 22, 2021
Article in press: June 22, 2021
Published online: July 28, 2021
ARTICLE HIGHLIGHTS
Research background
Y-box binding protein 1 (YB-1) promotes the proliferation of tumor cells, inhibits apoptosis, and activates the expression of multidrug resistance genes in breast cancer, kidney cancer and other cancers. It can also promote the resistance of gefitinib in lung adenocarcinoma cells. The specific molecular mechanism of YB-1 mediating drug resistance in hepatocellular carcinoma (HCC) is still unclear.
Research motivation
The study will provide a basis for the application of YB-1 in sorafenib resistance of HCC.
Research objectives
To detect the expression of YB-1 in HCC tissues and cells, and explore the role and the potential mechanism of YB-1 in sorafenib resistance of HCC.
Research methods
In this study, the authors examined the expression levels of YB-1 in cancer and corresponding paracancerous tissues of HCC patients, and clarified whether YB-1 was involved in sorafenib resistance in HCC by overexpressing and knocking down YB-1 in two kinds of hepatoma cell lines. Furthermore, a nude mouse liver cancer xenograft tumor model was established to verify the role of YB-1 in mediating sorafenib resistance in HCC in vivo. The signaling pathways involved in YB-1-mediated drug resistance in hepatocarcinoma cells were also screened and validated by digital expression profiling (DGE) technology.
Research results
YB-1 expression levels were significantly upregulated in both cancer tissues of HCC patients and human hepatoma cell lines. YB-1 could resist the effects of sorafenib on proliferation and apoptosis in hepatocarcinoma cells, which in turn mediated the resistance of HCC cells to sorafenib. YB-1 mediates sorafenib resistance in hepatocarcinoma cells through activating the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.
Research conclusions
Knockdown of YB-1 can effectively inhibit the occurrence of sorafenib resistance, and can also enhance the inactivation of sorafenib on the PI3K/Akt signaling pathway. Therefore, YB-1 is a sorafenib resistance related gene.
Research perspectives
Downregulation of YB-1 may be a new potential method for the treatment of advanced HCC, and it is expected to improve the efficacy of sorafenib in the treatment of advanced HCC patients.
