Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2023; 29(19): 2932-2949
Published online May 21, 2023. doi: 10.3748/wjg.v29.i19.2932
TATA-box-binding protein-associated factor 15 is a novel biomarker that promotes cell proliferation and migration in gastrointestinal stromal tumor
Cheng-Ming Guo, Li Tang, Xu Li, Liu-Ye Huang
Cheng-Ming Guo, Li Tang, Xu Li, Liu-Ye Huang, Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong Province, China
Author contributions: Guo CM and Tang L contributed equally to this work; Guo CM and Tang L performed the data acquisition, drafted the manuscript and executed the in vitro experiments; Guo CM completed the statistical analyses; Guo CM and Li X executed the animal experiments; Huang LY designed the work and revised the manuscript.
Supported by National Natural Science Foundation of China, No. 81870453.
Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by Ethics Committee of Yantai Yuhuangding Hospital,No.2019-410.
Institutional animal care and use committee statement: All animal experiments were approved by the Affiliated Yantai Yuhuangding Hospital of Qingdao University for Laboratory Animal Welfare and Ethical Review, No. 2022-A56.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All authors report having no relevant conflicts of interest for this article.
Data sharing statement: The data can be obtained from the corresponding author upon reasonable request.
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: Liu-Ye Huang, Professor, Academic Research, Chief Doctor, Chief Physician, Research Scientist, Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai 264000, Shandong Province, China. liuye_huang@163.com
Received: November 28, 2022
Peer-review started: November 28, 2022
First decision: February 15, 2023
Revised: March 6, 2023
Accepted: April 11, 2023
Article in press: April 11, 2023
Published online: May 21, 2023
Processing time: 168 Days and 17.7 Hours
ARTICLE HIGHLIGHTS
Research background

Gastrointestinal stromal tumors (GIST) are a common neoplasm with high rates of recurrence and metastasis, and its therapeutic efficacy is still not ideal. There is an unmet need to find new molecular therapeutic targets for GIST. TATA-box-binding protein-associated factor 15 (TAF15) contributes to the progress of various tumors, while the role and molecular mechanism of TAF15 in GIST progression are still unknown.

Research motivation

To explore the novel early diagnostic markers or therapeutic targets for the diagnosis and treatment of GIST.

Research objectives

To investigate new molecular therapeutic targets for GIST and explore the role and potential molecular mechanism of TAF15 in GIST progression.

Research methods

Proteomic analysis was performed to explore the differentially expressed proteins in GIST. Western blotting and immunohistochemical analysis were used to verify expression levels of TAF15 in GIST tissues and cell lines. Cell counting kit-8, colony formation, transwell, wound healing and western blotting assays were applied to explore the effect and the molecular mechanism of TAF15 in GIST. The role of TAF15 in vivo was confirmed using a xenograft mouse model assay.

Research results

A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST. TAF15 was significantly upregulated in GIST tissues and cell lines. Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST. TAF15 knockdown suppressed proliferation and migration of GIST cells in vitro and inhibited the growth of GIST in vivo. Moreover, the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1, MEK and ERK1/2 in GIST cells and xenograft tissues, while the total levels of RAF1, MEK and ERK1/2 had no significant changes.

Research conclusions

TAF15 may contribute to malignant progression of GIST and promote cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.

Research perspectives

TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.