Decreased TMEM40 expression is associated with malignant behavior of cutaneous squamous cell carcinoma and inhibits tumor progression

Yu,Lei; Liu,Jie; Zhang,Tang-De; Zheng,Xiu-Fen; Luo,Dong-Lan; Zhu,Wei-Liang; Qiu,Xian-Wen; Guo,Lin-Lang

doi:10.3892/ol.2021.12867

Decreased TMEM40 expression is associated with malignant behavior of cutaneous squamous cell carcinoma and inhibits tumor progression

Authors:
- Lei Yu
- Jie Liu
- Tang-De Zhang
- Xiu-Fen Zheng
- Dong-Lan Luo
- Wei-Liang Zhu
- Xian-Wen Qiu
- Lin-Lang Guo
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Affiliations: Department of Dermatology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Clinical Laboratory, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China, Department of Dermatology, Shunde Hospital of Southern Medical University, Shunde, Guangdong 528308, P.R. China, Department of Dermatology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong 518028, P.R. China, Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Pathology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China
Published online on: June 15, 2021 https://doi.org/10.3892/ol.2021.12867
Article Number: 606
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer in humans worldwide. The identification and characterization of cancer‑associated transmembrane proteins are important for understanding the molecular biology of CSCC. The aim of the present study was to evaluate the expression pattern of transmembrane protein 40 (TMEM40) in CSCC and its clinical significance. The underlying mechanisms were also examined. Reverse transcription‑quantitative PCR, western blot and immunohistochemistry analysis were used to determine the relative expression of TMEM40 in CSCC cell lines and clinical tissue samples. The effect of TMEM40 gene silencing on cell proliferation was also evaluated using Cell Counting Kit‑8 assays. Wound healing assays, flow cytometry and Transwell assays were used to explore the migration, cell cycle distribution/apoptosis and invasion of CSCC cells following TMEM40 silencing, respectively. In the present study, increased TMEM40 expression was observed in CSCC tissue samples, compared with normal skin, and TMEM40 expression was associated with large tumor size in patients with CSCC. In vitro functional assays indicated that TMEM40 was involved in the regulation of A431 and SCL1 cell growth through its effects on the cell cycle and apoptosis. Silencing TMEM40 in A431 and SCL1 cells resulted in cell cycle arrest at the G0/G1 phase and promoted apoptosis. In addition, migration and invasion were significantly inhibited following silencing of TMEM40 expression in CSCC cells. Taken together, the results of the present study indicated that reduced TMEM40 expression could inhibit CSCC development and that TMEM40 may represent a therapeutic target in CSCC.

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