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
Abstract
BACKGROUND

Abnormal tuftelin 1 (TUFT1) has been reported in multiple cancers and exhibits oncogenic roles in tumor progression. However, limited data are available on the relationship between TUFT1 and hepatocellular carcinoma (HCC), and the exact biological mechanism of TUFT1 is still poorly understood in HCC.

AIM

To investigate TUFT1 expression in HCC and how interfering TUFT1 transcription affects HCC growth.

METHODS

TUFT1 in HCC and non-HCC tissues based on databases of the Cancer Genome Atlas and Oncomine were analyzed, and TUFT1 in human HCC tissues on microarray were detected by immunohistochemistry for clinicopathological features, overall survival, and disease-free survival. HCC cells were transfected with constructed vectors of TUFT1 that interfere or over-express TUFT1 for analyzing the biological behaviors of HCC cells. Proliferation, invasion, migration, and apoptosis of cells were detected by cell counting kit-8, scratch assay, transwell tests, and flow cytometry and confirmed by Western blotting, respectively.

RESULTS

Abnormal TUFT1 levels in databases expressed in HCC at messenger RNA (mRNA) level and HCC tissues were mainly located in cytoplasm and membrane. The level of TUFT1 expression in the HCC group was significantly higher (χ2 = 18.563, P < 0.001) than that in the non-cancerous group, closely related to clinical staging, size, vascular invasion of tumor, hepatitis B e-antigen positive, and ascites (P < 0.01) of HCC patients, and negatively to HCC patients’ overall survival and disease-free survival (P < 0.001). After interfering with TUFT1 transcription at mRNA level in the MHCC-97H cells by the specific TUFT1-short hairpin RNA, cell proliferation, invasion, and metastasis were significantly inhibited with increasing apoptosis rate. In contrast, proliferation, invasion, and migration were significantly enhanced after over-expression of TUFT1 mRNA in Hep3B cells in vitro.

CONCLUSION

Oncogenic TUFT1 was associated with the progression of HCC and could be a potential molecular-target for inhibiting HCC growth.

Keywords: Hepatocellular carcinoma, Tuftelin 1, Prognosis, Molecular-target, Growth

Core Tip: Tuftelin1 (TUFT1) has been reported to be regulated by hypoxia and involved in the Hedgehog signaling pathway, with over-expression in hepatocellular carcinoma (HCC) tissues or cell lines. Abnormal TUFT1 level was significantly related to tumor size, vascular invasion, positive hepatitis B e-antigen, advanced tumor-node-metastasis stage of HCC, patients with ascites, and shorter overall survival and disease-free survival. Interfering TUFT1 transcription could markedly suppress the growth and metastasis of high TUFT1 MHCC-97H cell lines in vitro through accelerating apoptosis. Moreover, increasing TUFT1 expression might promote the growth and metastasis of low TUFT1 Hep3B cell lines in vitro. The data suggested that TUFT1 is involved in HCC progression via the mechanism of inhibiting apoptosis and might serve as a potential therapeutic target for inhibiting HCC growth.