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

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.

SYT12 is a novel oncogene that promotes thyroid carcinoma progression and metastasis

“…To discover a gene that associates with PTC that could differentiate low-risk and high-risk PTC patients, we send 39 paired PTC samples for RNA sequencing and discovered that SYT12 was overexpressed in PTC tissues associated with nearby non-neoplastic thyroid tissues. There are a few reports about SYT12, and it has been found that played a crucial role in some cancers such as oral cancer and lung adenocarcinoma [10,11]. Jonklaas et al also showed that SYT12 could predict papillary thyroid cancer outcomes in a prospective cohort [12].…”

“…In recent years, variants of the human SYT12 were shown to be associated with some cancers [10,11]. Liu et al reported that SYT12 acted as a possible oncogene by activating the PI3K-AKT-mTOR signal channel in lung adenocarcinoma [11].…”

“…Liu et al reported that SYT12 acted as a possible oncogene by activating the PI3K-AKT-mTOR signal channel in lung adenocarcinoma [11]. Keitaro et al also found that SYT12 played a crucial part in oral carcinoma and might be an innovative therapeutic target [10]. And Jonklaas et al showed that SYT12 may contribute to predicting PTC results in a prospective cohort, but they did not verify the specific biological functions by biology empirical study [12].…”

Tumor Suppressive Circular RNA-102450: Development of a Novel Diagnostic Procedure for Lymph Node Metastasis from Oral Cancer

“…Three human OSCC-derived cell lines (HSC-3, Sa3, and SAS) were purchased from RIKEN BioResource Center (Tsukuba, Japan) and the Japanese Collection of Research Bioresources Cell Bank (Ibaraki, Japan). We obtained human normal oral keratinocytes (HNOKs) from young healthy patients and cultured the cells as described previously [13][14][15][16]. All cells were used within seven passages after thawing.…”

The dysregulated expression and functional effect of CaMK2 in cancer

“…Finally, the possible involvement of regulation of CaMK2 signaling in the progression of oral squamous cell carcinoma (OSCC) and glioblastoma multiforme (GBM) has also been reported in two other studies. One of these studies showed a positive correlation between CaMK2 activation and cancer progression in OSCC [ 59 ]. Synaptotagmin12 (SYT12) expression in primary OSCC tissue and OSCC-derived cell lines was significantly increased compared to that in normal tissues.…”