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Article

The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma

by
Chung-Chih Tseng
1,2,†,
Chung-Ching Hung
3,†,
Chih-Wen Shu
4,
Cheng-Hsin Lee
5,
Chun-Feng Chen
6,
Mei-Shu Kuo
7,
Yu-Ying Kao
7,
Chun-Lin Chen
8,
Luo-Ping Ger
9 and
Pei-Feng Liu
5,10,11,12,*
1
Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
2
Department of Dentistry, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan
3
Department of Otolaryngology, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan
4
Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
5
Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
6
Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
7
Department of Biotechnology, Chia Nan University, Tainan 71710, Taiwan
8
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
9
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
10
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
11
Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
12
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
 
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*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2023, 11(5), 1270; https://doi.org/10.3390/biomedicines11051270
Submission received: 23 March 2023 / Revised: 7 April 2023 / Accepted: 23 April 2023 / Published: 25 April 2023
(This article belongs to the Special Issue Head and Neck Cancer: From Molecular Characterization to Therapy)
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Abstract

There are currently no effective biomarkers for the diagnosis and treatment of tongue squamous cell carcinoma (TSCC), which causes a poor 5-year overall survival rate. Thus, it is crucial to identify more effective diagnostic/prognostic biomarkers and therapeutic targets for TSCC patients. The receptor expression-enhancing protein 6 (REEP6), a transmembrane endoplasmic reticulum resident protein, controls the expression or transport of a subset of proteins or receptors. Although it was reported that REEP6 plays a role in lung and colon cancers, its clinical impact and biological role in TSCC are still unknown. The present study aimed to identify a novel effective biomarker and therapeutic target for TSCC patients. Expression levels of REEP6 in specimens from TSCC patients were determined with immunohistochemistry. Gene knockdown was used to evaluate the effects of REEP6 in cancer malignancy (colony/tumorsphere formation, cell cycle regulation, migration, drug resistance and cancer stemness) of TSCC cells. The clinical impact of REEP6 expression and gene co-expression on prognosis were analyzed in oral cancer patients including TSCC patients from The Cancer Genome Atlas database. Tumor tissues had higher levels of REEP6 compared to normal tissues in TSCC patients. Higher REEP6 expression was related to shorter disease-free survival (DFS) in oral cancer patients with poorly differentiated tumor cells. REEP6-knocked-down TSCC cells showed diminished colony/tumorsphere formation, and they also caused G1 arrest and decreased migration, drug resistance and cancer stemness. A high co-expression of REEP6/epithelial–mesenchymal transition or cancer stemness markers also resulted in poor DFS in oral cancer patients. Thus, REEP6 is involved in the malignancy of TSCC and might serve as a potential diagnostic/prognostic biomarker and therapeutic target for TSCC patients.
Keywords: tongue squamous cell carcinoma; receptor expression-enhancing protein 6; malignancy; prognosis tongue squamous cell carcinoma; receptor expression-enhancing protein 6; malignancy; prognosis

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MDPI and ACS Style

Tseng, C.-C.; Hung, C.-C.; Shu, C.-W.; Lee, C.-H.; Chen, C.-F.; Kuo, M.-S.; Kao, Y.-Y.; Chen, C.-L.; Ger, L.-P.; Liu, P.-F. The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma. Biomedicines 2023, 11, 1270. https://doi.org/10.3390/biomedicines11051270

AMA Style

Tseng C-C, Hung C-C, Shu C-W, Lee C-H, Chen C-F, Kuo M-S, Kao Y-Y, Chen C-L, Ger L-P, Liu P-F. The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma. Biomedicines. 2023; 11(5):1270. https://doi.org/10.3390/biomedicines11051270

Chicago/Turabian Style

Tseng, Chung-Chih, Chung-Ching Hung, Chih-Wen Shu, Cheng-Hsin Lee, Chun-Feng Chen, Mei-Shu Kuo, Yu-Ying Kao, Chun-Lin Chen, Luo-Ping Ger, and Pei-Feng Liu. 2023. "The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma" Biomedicines 11, no. 5: 1270. https://doi.org/10.3390/biomedicines11051270

APA Style

Tseng, C.-C., Hung, C.-C., Shu, C.-W., Lee, C.-H., Chen, C.-F., Kuo, M.-S., Kao, Y.-Y., Chen, C.-L., Ger, L.-P., & Liu, P.-F. (2023). The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma. Biomedicines, 11(5), 1270. https://doi.org/10.3390/biomedicines11051270

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