Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2021; 27(23): 3327-3341
Published online Jun 21, 2021. doi: 10.3748/wjg.v27.i23.3327
Oncogenic tuftelin 1 as a potential molecular-targeted for inhibiting hepatocellular carcinoma growth
Meng-Na Wu, Wen-Jie Zheng, Wen-Xin Ye, Li Wang, Ying Chen, Jie Yang, Deng-Fu Yao, Min Yao
Meng-Na Wu, Wen-Jie Zheng, Deng-Fu Yao, Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Wen-Xin Ye, Min Yao, Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
Li Wang, Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
Ying Chen, Department of Oncology, The Affiliated Second Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Jie Yang, Department of Molecular Biology, Life Science School of Nantong University, Nantong 226009, Jiangsu Province, China
Author contributions: Wu MN, Zheng WJ, and Ye WX contributed equally to this work and wrote the first draft; Wang L, Chen Y, and Yang J contributed to the methodology, data curation, and formal analysis; Yao M and Yao DF revised the manuscript. All authors approved the final version of the manuscript.
Supported by Projects of the Ministry of Science and Technology, National Key Research and Development Program, No. 2018YFC0116902; National Natural Science Foundation of China, No. 81673241, No. 31872738, No. 81873915.
Institutional review board statement: This study was approved by the Ethics Committee of the Affiliated Hospital of Nantong University (TDFY2018-025), China.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: No additional data are available.
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: Deng-Fu Yao, MD, PhD, Director, Full Professor, Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong 226001, Jiangsu Province, China. yaodf@ahnmc.com
Received: December 14, 2020
Peer-review started: December 14, 2020
First decision: December 27, 2020
Revised: January 6, 2021
Accepted: May 19, 2021
Article in press: May 19, 2021
Published online: June 21, 2021
Processing time: 185 Days and 22.1 Hours
ARTICLE HIGHLIGHTS
Research background

Tuftelin 1 (TUFT1) has been reported to be elevated in multiple cancer types, and its abnormal expression has attracted medical attention as a novel oncogenic biomarker. However, the relationship between TUFT1 and hepatocellular carcinoma (HCC) remains to be identified. In this study, the levels of TUFT1 in HCC tissues were investigated and the roles of TUFT1 expression were explored in vitro by intervening in TUFT1 activation of HCC cell lines.

Research motivation

TUFT1 was first identified and sequenced from a bovine ameloblast-enriched complementary DNA library with a highly conserved gene localized in chromosome 1q21-31 that contained 13 exons, encoding an acidic, phosphorylated glycoprotein of 390 amino acids, and it plays a critical role in the development and mineralization of enamel. Recently, TUFT1 has been reported to be elevated in multiple cancers, and abnormal TUFT1 has attracted medical attention for HCC. However, limited data is available on the relationship between TUFT1 and HCC, and the exact biological mechanism of TUFT1 is still poorly understood in HCC.

Research objectives

The pathogenesis and feasible therapeutic treatments of HCC need urgent investigation. Abnormal TUFT1 has been reported in multiple cancers, and it exhibits oncogenic roles in tumor progression. In this study, the landscape of TUFT1 expression in human HCC tissues was investigated, and its mechanism was confirmed through intervening or over-expressing TUFT1 activation in vitro.

Research methods

TUFT1 on databases of the Cancer Genome Atlas and Oncomine or in HCC tissues were analyzed for clinicopathological features, overall survival, and disease-free survival. High and low expressing HCC cell lines were screened among different HCC cell lines and transfected with constructed vectors that interfere or over-express TUFT1 to analyze biological behaviors. Proliferation, invasion, migration, and apoptosis of cells were detected by CCK-8, scratch assay, transwell tests, and flow cytometry, respectively, and confirmed by Western blotting.

Research results

The research results confirmed that TUFT1 was over-expressed in HCC tissues, and its expression was significantly related to tumor size, vascular invasion, positive hepatitis B e-antigen, advanced tumor-node-metastasis staging, ascites, shorter overall survival, and disease-free survival of HCC patients. Novel findings were that interfering with TUFT1 gene transcription could markedly suppress the proliferation and metastasis of the higher TUFT1 MHCC-97H cell lines through an apoptosis mechanism. Moreover, over-expressing TUFT1 promoted the growth and metastasis of the lower TUFT1 Hep3B cell lines in vitro.

Research conclusions

Based on human specimen studies, high TUFT1 levels were associated with HCC progression, inhibiting TUFT1 affected proliferation and metastasis, over-expressing TUFT1 promoted proliferation and metastasis, and interfering activation of TUFT1 led to significant increase in cell apoptosis. TUFT1 could be a novel useful target for HCC effective therapy.

Research perspectives

Basic and clinical studies have confirmed that the alterations of oncogenic TUFT1 expression might promote HCC growth and metastasis via an anti-apoptotic mechanism, and abnormal TUFT1 level could be a new prognostic marker or potential molecular target for HCC therapy. More studies in the future are needed to clarify the molecular mechanisms underlying TUFT1 up-regulation contribution to the progression of HCC.