Hechen Wang1,2, Tianyu Wang2, Zeying Zhang1, Yu Fan3, Lan Zhang4, Kuan Gao2, Shuya Luo2, Qinghuan Xiao5, Changfu Sun6. 1. Liaoning Provincial Key Laboratory of Oral Diseases, Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, 117 Nanjing Bei Jie, Heping District, Shenyang,, 110002, Liaoning, China. 2. Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, China. 3. Liaoning Provincial Key Laboratory of Oral Diseases, Department of Pathology, School and Hospital of Stomatology, China Medical University, Shenyang, China. 4. Liaoning Provincial Key Laboratory of Oral Diseases, Hospital Infection Management Office, School and Hospital of Stomatology, China Medical University, Shenyang, China. 5. Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, China. qinghuanxiao12345@163.com. 6. Liaoning Provincial Key Laboratory of Oral Diseases, Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, 117 Nanjing Bei Jie, Heping District, Shenyang,, 110002, Liaoning, China. changfusun@hotmail.com.
Abstract
PURPOSE: Ca2+-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear. METHODS: In this study, we explored the role of TMEM16A expression in human OSCC tissues using both TCGA dataset and immunohistochemistry. CCK-8 assay was applied to evaluate cell proliferation. Patch clamp technique was applied to record TMEM16A Cl- currents. RESULTS: We found that high TMEM16A expression is related with large tumor size, lymph node metastasis, and poor clinical outcome in patients with OSCC. In addition, TMEM16A overexpression could promote cell proliferation, and inhibition of TMEM16A channel activities could suppress cell proliferation in OSCC cells. Furthermore, simvastatin could suppress TMEM16A channel activities, and inhibited cell proliferation in OSCC cells via TMEM16A. CONCLUSION: Our findings identify a novel anti-tumor mechanism of simvastatin by targeting TMEM16A. Simvastatin may represent an innovative strategy for treating OSCC with high TMEM16A expression.
PURPOSE: Ca2+-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear. METHODS: In this study, we explored the role of TMEM16A expression in human OSCC tissues using both TCGA dataset and immunohistochemistry. CCK-8 assay was applied to evaluate cell proliferation. Patch clamp technique was applied to record TMEM16A Cl- currents. RESULTS: We found that high TMEM16A expression is related with large tumor size, lymph node metastasis, and poor clinical outcome in patients with OSCC. In addition, TMEM16A overexpression could promote cell proliferation, and inhibition of TMEM16A channel activities could suppress cell proliferation in OSCC cells. Furthermore, simvastatin could suppress TMEM16A channel activities, and inhibited cell proliferation in OSCC cells via TMEM16A. CONCLUSION: Our findings identify a novel anti-tumor mechanism of simvastatin by targeting TMEM16A. Simvastatin may represent an innovative strategy for treating OSCC with high TMEM16A expression.
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