J Cancer 2019; 10(20):4913-4920. doi:10.7150/jca.32582

Research Paper

SYT12 plays a critical role in oral cancer and may be a novel therapeutic target

Keitaro Eizuka1, Dai Nakashima1, Noritoshi Oka1, Sho Wagai1, Toshikazu Takahara2, Tomoaki Saito2, Kazuyuki Koike2, Atsushi Kasamatsu2,✉, Masashi Shiiba3, Hideki Tanzawa1,2, Katsuhiro Uzawa1,2,✉

1. Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan
2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan
3. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

Abstract

Synaptotagmin12 (SYT12) has been well characterized as the regulator of transmitter release in the nervous system, however the relevance and molecular mechanisms of SYT12 in oral squamous cell carcinoma (OSCC) are not understood. In the current study, we investigated the expression of SYT12 and its molecular biological functions in OSCC by quantitative reverse transcriptase polymerase chain reaction, immunoblot analysis, and immunohistochemistry. SYT12 were up-regulated significantly in OSCC-derived cell lines and primary OSCC tissue compared with the normal counterparts (P<0.05) and the SYT12 expression levels were correlated significantly with clinical indicators, such as the primary tumoral size, lymph node metastasis, and TNM stage (P<0.05). SYT12 knockdown OSCC cells showed depressed cellular proliferation, migration, and invasion with cell cycle arrest at G1 phase. Surprisingly, we found increased calcium/calmodulin-dependent protein kinase 2 (CAMK2) inhibitor 1 (CAMK2N1) and decreased CAMK2-phosphorylation in the knockdown cells. Furthermore, treatment with L-3, 4-dihydroxyphenylalanine (L-dopa), a drug approved for Parkinson's disease, led to down-regulation of SYT12 and similar phenotypes to SYT12 knockdown cells. Taken together, we concluded that SYT12 plays a significant role in OSCC progression via CAMK2N1 and CAMK2, and that L-dopa would be a new drug for OSCC treatment through the SYT12 expression.

Keywords: Oral squamous cell carcinoma, SYT12, CAMK2N1, CAMK2, L-dopa

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How to cite this article:
Eizuka K, Nakashima D, Oka N, Wagai S, Takahara T, Saito T, Koike K, Kasamatsu A, Shiiba M, Tanzawa H, Uzawa K. SYT12 plays a critical role in oral cancer and may be a novel therapeutic target. J Cancer 2019; 10(20):4913-4920. doi:10.7150/jca.32582. Available from http://www.jcancer.org/v10p4913.htm