Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2023; 15(3): 490-503
Published online Mar 15, 2023. doi: 10.4251/wjgo.v15.i3.490
F-box and leucine-rich repeat 6 promotes gastric cancer progression via the promotion of epithelial-mesenchymal transition
Lei Meng, Yu-Ting Hu, A-Man Xu
Lei Meng, A-Man Xu, Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Yu-Ting Hu, Department of Immunology, College of Basic Medicine, Anhui Medical University, Hefei 230022, Anhui Province, China
Author contributions: Meng L collected the data and wrote the manuscript; Hu YT participated in the discussion; Xu AM reviewed the manuscript and provided funding support; all authors contributed to the article and approved the submitted version.
Supported by the Key Research and Development Program of Anhui Province, No. 202104J07020029.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the First Affiliated Hospital of Anhui Medical University (Approval No. Quick PJ 2019-10-11).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by Anhui Medical University Laboratory Animal Ethics Committee (Approval No. LLSC20200513).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There is no conflict of interest in this 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:
Corresponding author: A-Man Xu, Doctor, PhD, Chief Physician, Full Professor, Department of General Surgery, First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Avenue, Shushan District, Hefei 230022, Anhui Province, China.
Received: December 4, 2022
Peer-review started: December 4, 2022
First decision: December 24, 2022
Revised: January 6, 2023
Accepted: February 14, 2023
Article in press: February 14, 2023
Published online: March 15, 2023

F-box and leucine-rich repeat 6 (FBXL6) have reportedly been associated with several cancer types. However, the role and mechanisms of FBXL6 in gastric cancer (GC) require further elucidation.


To investigate the effect of FBXL6 in GC tissues and cells and the underlying mechanisms.


TCGA and GEO database analysis was performed to evaluate the expression of FBXL6 in GC tissues and adjacent normal tissues. Reverse transcription-quantitative polymerase chain reaction, immunofluorescence, and western blotting were used to detect the expression of FBXL6 in GC tissue and cell lines. Cell clone formation, 5-ethynyl-2’-deoxyuridine (EdU) assays, CCK-8, transwell migration assay, and wound healing assays were performed to evaluate the malignant biological behavior in GC cell lines after transfection with FBXL6-shRNA and the overexpression of FBXL6 plasmids. Furthermore, in vivo tumor assays were performed to prove whether FBXL6 promoted cell proliferation in vivo.


FBXL6 expression was upregulated more in tumor tissues than in adjacent normal tissues and positively associated with clinicopathological characteristics. The outcomes of CCK-8, clone formation, and Edu assays demonstrated that FBXL6 knockdown inhibited cell proliferation, whereas upregulation of FBXL6 promoted proliferation in GC cells. Additionally, the transwell migration assay revealed that FBXL6 knockdown suppressed migration and invasion, whereas the overexpression of FBXL6 showed the opposite results. Through the subcutaneous tumor implantation assay, it was evident that the knockdown of FBXL6 inhibited GC graft tumor growth in vivo. Western blotting showed that the effects of FBXL6 on the expression of the proteins associated with the epithelial-mesenchymal transition-associated proteins in GC cells.


Silencing of FBXL6 inactivated the EMT pathway to suppress GC malignancy in vitro. FBXL6 can potentially be used for the diagnosis and targeted therapy of patients with GC.

Keywords: Gastric cancer, F-box and leucine-rich repeat 6, Invasion, Epithelial-mesenchymal transition, Metastasis

Core Tip: F-box and leucine-rich repeat 6 (FBXL6) is up-regulated in gastric cancer (GC) cell lines and tissues, which is correlated with tumor size, grade of differentiation, and TNM stage. Knockdown of TRIM55 in GC cells suppressed proliferation, migration and invasion of cells and affected the expression of cell epithelial-mesenchymal transition-related proteins. Our study provides novel evidence that FBXL6 contributes the growth and metastasis of GC.