Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2022; 14(12): 2353-2366
Published online Dec 15, 2022. doi: 10.4251/wjgo.v14.i12.2353
Anti-silencing function 1B knockdown suppresses the malignant phenotype of colorectal cancer by inactivating the phosphatidylinositol 3-kinase/AKT pathway
Gen-Hua Yu, Xu-Feng Gong, Ying-Ying Peng, Jun Qian
Gen-Hua Yu, Xu-Feng Gong, Ying-Ying Peng, Department of Radiation Oncology, Zhebei Mingzhou Hospital, Huzhou 313000, Zhejiang Province, China
Jun Qian, Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, Zhejiang Province, China
Author contributions: Yu GH, Gong XF and Qian J were involved in the conceptualization; Peng YY and Qian J contributed to the formal analysis and investigation; Yu GH and Gong XF wrote the original draft.
Supported by Huzhou Science and Technology Bureau Foundation, No. 2018GY09.
Institutional review board statement: The current study received permission from the Ethics Committee of Zhebei Mingzhou Hospital (ZBMZYYLL211028).
Institutional animal care and use committee statement: Animal experiments obtained permission from the Institutional Animal Care and Use Committee of Beijing Viewsolid Biotechnology Co., Ltd (VS212601454), which complied with the National Institutes of Health Guide for the Care and Use of Laboratory Animals as well as ARRIVE guidelines.
Informed consent statement: All subjects signed informed consents.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All the data used to support the findings of this study are included within the article.
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: Jun Qian, MD, PhD, Professor, Surgeon, Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), No. 1 Banshan East Road, Gongshu District, Hangzhou 310022, Zhejiang Province, China. qianj1973@aliyun.com
Received: June 29, 2022
Peer-review started: June 29, 2022
First decision: August 6, 2022
Revised: August 31, 2022
Accepted: November 4, 2022
Article in press: November 4, 2022
Published online: December 15, 2022
Abstract
BACKGROUND

Mounting studies have highlighted the pivotal influence of anti-silencing function 1B (ASF1B) on the malignancy of cancers.

AIM

To explore the influence and mechanism of ASF1B in colorectal cancer (CRC).

METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA expression of ASF1B. Immunohistochemical staining was performed to detect protein expression of ASF1B and Ki67 in tumor tissues. Western blot analysis was used to determine levels of ASF1B and proliferation/epithelial mesenchymal transition (EMT)/stemness-related proteins. In addition, the proliferation of CRC cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2’-Deoxyuridine assays. The migration and invasion of CRC cells were evaluated using transwell assays. Stemness of CRC cells was tested using the sphere formation assay. To construct a xenograft tumor model, HCT116 cells were introduced into mouse flanks via subcutaneous injection.

RESULTS

ASF1B expression was markedly increased in CRC tissues and cells, and it was inversely correlated with overall survival of CRC patients and was positively associated with the tumor node metastasis (TNM) stage of CRC patients. Silencing of ASF1B suppressed proliferation, migration, invasion, stemness and EMT of CRC cells as well as tumorigenesis of xenograft mice. Furthermore, protein levels of P-phosphatidylinositol 3-kinase (p-PI3K) and p-AKT were decreased after silencing of ASF1B in CRC cells. The inhibitory effects of ASF1B knockdown on cell proliferation, stemness and EMT were partly abolished by PI3K activator in CRC cells.

CONCLUSION

Silencing of ASF1B inactivated the PI3K/AKT pathway to suppress CRC malignancy in vitro.

Keywords: Colorectal cancer, Anti-silencing function 1B, Phosphatidylinositol 3-kinase/AKT, Stemness, Epithelial mesenchymal transition

Core Tip: Anti-silencing function 1B (ASF1B) expression was increased in colorectal cancer (CRC) tissues and cells, and was negatively associated with prognosis of CRC patients. Functionally, ASF1B knockdown repressed the malignant behaviors of CRC cells in vitro and tumorigenesis in vivo, therefore having potential for CRC treatment. Moreover, our findings showed that ASF1B down-regulation suppressed the malignant behaviors of CRC cells by inactivating the PI3K/AKT pathway.