Synaptotagmin-7 Research Articles

G-Quadruplex-Mediated Transcriptional Regulation of SYT7: Implications for Tumor Progression and Therapeutic Strategies.

Synaptotagmin 7 (SYT7), a member of the synaptotagmin family, exhibits high expression in various tumors and is closely associated with patient prognosis. The tight regulation of SYT7 expression assumes paramount significance in the progression of tumorigenesis. In this study, we detected a high GC content in the first 1000 bp of the promoter region of SYT7, suggesting a potential role of the G-quadruplex in its transcriptional regulation. Circular dichroism spectroscopy results showed that -187 to -172 bp sequence can form a typical parallel G-quadruplex structure, and site mutation revealed the critical role of the ninth guanine in its formation. Then, treatment of two ligands of G-quadruplex (TMPyP4 and Pyridostatin) reduced both the expression of SYT7 and subsequent tumor proliferation, demonstrating the potential of the G-quadruplex as a targeted therapy for tumors. By shedding light on the pivotal role of the G-quadruplex in regulating SYT7 transcription, our study not only advances our comprehension of this intricate regulatory mechanism but also emphasizes the significance of SYT7 in tumor proliferation. These findings collectively contribute to a more comprehensive understanding of the interplay between G-quadruplex regulation and SYT7 function in tumor development.

Double-strand-break repair protein rad21 homolog/Synaptotagmin-7 alleviates Alzheimer's disease in mice by promoting M2 polarization of microglia

Synaptotagmin-7 (SYT7) has been proposed as an innovative therapeutic strategy for treating cognitive impairment, while its contribution to Alzheimer’s disease (AD) alleviation remains unclear. In this study, we investigated the role and potential mechanisms of SYT7 in AD. APP/PS1 mice were induced as an AD mouse model, and RNA-sequencing was conducted to analyze the transcriptomic differences between the brain tissues of AD mice and controls. SYT7, which was the most significantly differentially expressed gene in the RNA-sequencing, was found to be reduced in AD-like mice, and overexpression of SYT7 alleviated cognitive dysfunction and attenuated neuroinflammation and neuronal loss in the hippocampal tissues of mice with AD. Transcription factor double-strand-break repair protein rad21 homolog (RAD21) bound to the promoter of SYT7 to activate SYT7 transcription. SYT7 and RAD21 were expressed in microglia. SYT7 and RAD21 both promoted M2 polarization of microglia, while silencing of SYT7 repressed the M2 polarization of microglia in the presence of RAD21 overexpression. Overall, our results indicate that RAD21 mediated transcriptional activation of SYT7 to promote M2 polarization of microglia, thereby alleviating AD-like symptoms in mice, which might provide prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course.

SYT7 (synaptotagmin 7) promotes cervical squamous cell carcinoma

Cervical squamous cell carcinoma (CESC) ranks among the primary contributors to global cancer-associated mortality. However, the role mediated by synaptotagmin 7 (SYT7) in CESC remains unclear. Our study employed immunohistochemistry to assess the level of SYT7 expression in the tissue microarray. Furthermore, lentiviral shRNA transduction was utilized to establish SYT7 knockdown cell line models based on HeLa and SiHa cell lines. The functional impacts of silencing SYT7 expression in vitro were evaluated. A subcutaneous xenograft model was employed to examine the tumorigenic potential of cells with or without SYT7. The content of SYT7 in CESC tissues was significantly elevated compared to adjacent normal tissues. Functionally, silencing SYT7 in HeLa and SiHa cells suppressed cell proliferation, colony formation ability, and apoptosis enhancement. Additionally, cells with suppressed SYT7 also exhibited inhibited cell migration and invasion. In vivo experiments demonstrated the loss of tumorigenic ability in SYT7 knockdown cells and suppressed tumor growth. Quantitative PCR PrimeView PathArray and apoptosis antibody array analyses revealed that upon elimination of SYT7, there was a significant upregulation observed in Caspase 8, TNF-R1 (TNF receptor superfamily member 1A), and HSPA5 (heat shock protein family A [Hsp70] member 5), while TGFBI (transforming growth factor beta-induced), RPL31 (ribosomal protein L31), LUM (lumican), HSDL2 (hydroxysteroid dehydrogenase-like 2), ITGB5 (integrin subunit beta 5), and Smad2 (SMAD family member2) were downregulated. Overall, we have demonstrated the tumor-promoting functions of SYT7 in CESC.

SYT7 is a key player in increasing exosome secretion and promoting angiogenesis in non-small-cell lung cancer

Lung cancer is the leading cause of cancer-related mortality, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Our previous study confirmed that synaptotagmin 7 (SYT7) promoted NSCLC metastasis in vivo and in vitro. Studies have shown that SYT7 is an important regulatory molecule of exocytosis in various cells. However, the characteristics of SYT7 across cancers and the function of SYT7 in tumor exosome secretion remain unclear. In this study, we conducted systematic pancancer analyses of SYT7, namely, analyses of expression patterns, diagnostic and prognostic values, genetic alterations, methylation, immune infiltration, and potential biological pathways. Furthermore, we demonstrated that SYT7 increased the secretion of exosomes from A549 and H1299 cells, promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs). Notably, SYT7 promoted angiogenesis by transferring exosomes containing the molecule centrosomal protein of 55 kDa (CEP55) protein to HUVECs. The CEP55 protein levels was downregulated in STAT1 inhibitor-treating SYT7-overexpresion NSCLC cells. We further found that SYT7 activated the mTOR signaling pathway through the downstream molecule CEP55, thereby promoting the invasion and metastasis of NSCLC cells. SYT7 promoted exosome secretion by NSCLC cells through upregulating syntaxin-1a and syntaxin-3. In vivo, SYT7 promoted the tumorigenesis, angiogenesis and metastasis of A549 cells through the exosome pathway. Our study is of great importance for understanding the mechanism of tumor exosome secretion and the role of exosomes in tumor progression.

SYT7 regulates the progression of chronic lymphocytic leukemia through interacting and regulating KNTC1

BackgroundChronic lymphocytic leukemia (CLL) is one of the most frequent occurring types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. At present, the molecular mechanism driving the pathogenesis and progression of CLL is not fully understood. The protein Synaptotagmin 7 (SYT7) encoded by the SYT7 gene has been found to be closely related to the development of various solid tumors, but its role in CLL is unclear. In this study, we investigated the function and molecular mechanism of SYT7 in CLL.MethodsThe expression level of SYT7 in CLL was determined by immunohistochemical staining and qPCR. The role of SYT7 in promoting CLL development was verified by in vivo and in vitro experiments. The molecular mechanism of SYT7 in CLL was elucidated by methods such as GeneChip analysis and Co-immunoprecipitation assay.ResultsMalignant behaviors such as proliferation, migration, and anti-apoptosis of CLL cells were significantly inhibited after SYT7 gene knockdown. In contrast, SYT7 overexpression promoted CLL development in vitro. Consistently, the knockdown of SYT7 also inhibited xenograft tumor growth of CLL cells. Mechanistically, SYT7 promoted CLL development by inhibiting SYVN1-mediated KNTC1 ubiquitination. The KNTC1 knockdown also attenuated the effects of SYT7 overexpression on development of CLL.ConclusionsSYT7 regulates the progression of CLL through SYVN1-mediated KNTC1 ubiquitination, which has potential value for molecular targeted therapy of CLL.

Excessive iron inhibits insulin secretion via perturbing transcriptional regulation of SYT7 by OGG1.

Although iron overload is closely related to the occurrence of type2diabetesmellitus (T2DM), the specific mechanism is unclear. Here, we found that excessive iron inhibited the secretion of insulin (INS) and impaired islet β cell function through downregulating Synaptotagmin 7 (SYT7) in iron overload model in vivo and in vitro. Our results further demonstrated that 8-oxoguanine DNA glycosylase (OGG1), a key protein in the DNA base excision repair, was an upstream regulator of SYT7. Interestingly, such regulation could be suppressed by excessive iron. Ogg1-null mice, iron overload mice and db/db mice exhibit reduced INS secretion, weakened β cell function and subsequently impaired glucose tolerance. Notably, SYT7 overexpression could rescue these phenotypes. Our data revealed an intrinsic mechanism by which excessive iron inhibits INS secretion through perturbing the transcriptional regulation of SYT7 by OGG1, which suggested that SYT7 was a potential target in clinical therapy for T2DM.

SYT7 promotes breast cancer cells growth through the PI3K/AKT pathway.

Breast cancer is one of the most malignant tumors in the reproductive system and has a poor prognosis. The aim of this study was to investigate the function and underlying mechanism of synaptotagmin 7 (SYT7) in breast cancer. We utilized The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter database to assess the correlation between SYT7 expression and the prognosis of breast cancer patients. The efficacy of SYT7 knockdown was evaluated through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Furthermore, we examined the impact of SYT7 on breast cancer cell proliferation and apoptosis using Cell Counting Kit-8 (CCK-8), clone formation assays, and flow cytometry. Through Western blot analysis, we investigated the influence of SYT7 on the expression of apoptosis-related markers and the PI3K/AKT signaling pathway in breast cancer. The TCGA database data analysis revealed a significant up-regulation of SYT7 expression in breast cancer tissues compared to normal tissues (P<0.001). A correlation was observed between SYT7 expression and tumor size (P=0.009), as well as estrogen receptor (ER) expression level (P<0.001) and progesterone receptor (PR) expression level (P<0.001) in breast cancer patients. Analysis of the Kaplan-Meier plotter database indicated that high SYT7 expression was associated with a shorter overall survival (OS) (P=0.009). The mRNA expression results indicated higher SYT7 expression in breast cancer tissues compared to adjacent normal tissues (P=0.005). CCK-8, clone formation assay, and flow cytometry results demonstrated that SYT7 promoted the proliferation and inhibited the apoptosis of breast cancer cells. Western blot assay confirmed the activation of PI3K/AKT signaling by SYT7. The findings suggest that SYT7 is highly expressed in breast cancer and that its high expression is linked to clinical characteristics and prognosis. Inhibition of SYT7 through knockdown can suppress proliferation and promote apoptosis of breast cancer cells, making it a potential target for breast cancer diagnosis and treatment.

Circ_0022340 promotes colorectal cancer progression via HNRNPC/EBF1/SYT7 or miR-382-5p/ELK1 axis

Circular RNAs (circRNAs) are characterized as a class of new noncoding RNAs and function in tumorigenesis of colorectal cancer (CRC). In our study, the molecule mechanism of circ_0022340 in CRC was investigated. For this aim, quantitative real-time polymerase chain reaction (RT-qPCR) was used to test gene expression in CRC cells. Cell function assays including 5-ethynyl-20-deoxyuridine (EdU), colony formation and transwell investigated the proliferation and migration capacity in CRC cells. Luciferase reporter and RNA immunoprecipitation (RIP)assays determined the interaction between circRNA, miRNA and mRNA. Western blot was used to test protein expression. An immunohistochemistry assay was used to assess the tumor growth in vivo. Results showed that Circ_0022340 was highly expressed in CRC cells. Circ_0022340 was formed from exon 5 to 6 of the synaptotagmin 7 (SYT7). Silencing of circ_0022340 suppressed CRC cell proliferation and migration. Functionally, circ_0022340 recruited heterogeneous nuclear ribonucleoprotein C (HNRNPC) to stabilize EBF1 mRNA and thereby activated SYT7. Moreover, circ_0022340 targeted miR-382-5p to up-regulate ETS transcription factor ELK1 (ELK1). It is concluded that Circ_0022340 promoted colorectal cancer progression via recruiting HNRNPC to stabilize EBF1 mRNA and thereby activated SYT7 or miR-382-5p/ELK1 axis, which might provide a novel target for CRC treatment.

Poloxamer-188 Exacerbates Brain Amyloidosis, Presynaptic Dystrophies, and Pathogenic Microglial Activation in 5XFAD Mice.

Alzheimer's disease (AD) is initiated by aberrant accumulation of amyloid beta (Aβ) protein in the brain parenchyma. The microenvironment surrounding amyloid plaques is characterized by the swelling of presynaptic terminals (dystrophic neurites) associated with lysosomal dysfunction, microtubule disruption, and impaired axonal transport. Aβ-induced plasma membrane damage and calcium influx could be potential mechanisms underlying dystrophic neurite formation. We tested whether promoting membrane integrity by brain administration of a safe FDA approved surfactant molecule poloxamer-188 (P188) could attenuate AD pathology in vivo. Three-month-old 5XFAD male mice were administered several concentrations of P188 in the brain for 42 days with mini-osmotic pumps. After 42 days, mice were euthanized and assessed for amyloid pathology, dystrophic neurites, pathogenic microglia activation, tau phosphorylation, and lysosomal / vesicular trafficking markers in the brain. P188 was lethal at the highest concentration of 10mM. Lower concentrations of P188 (1.2, 12, and 120μM) were well tolerated. P188 increased brain Aβ burden, potentially through activation of the γ-secretase pathway. Dystrophic neurite pathology was exacerbated in P188 treated mice as indicated by increased LAMP1 accumulation around Aβ deposits. Pathogenic microglial activation was increased by P188. Total tau levels were decreased by P188. Lysosomal enzyme cathepsin D and calciumdependent vesicular trafficking regulator synaptotagmin-7 (SYT7) were dysregulated upon P188 administration. P188 brain delivery exacerbated amyloid pathology, dystrophic neurites, and pathogenic microglial activation in 5XFAD mice. These effects correlated with lysosomal dysfunction and dysregulation of plasma membrane vesicular trafficking. P188 is not a promising therapeutic strategy against AD pathogenesis.

Synaptotagmin 7 is targeted to the axonal plasma membrane through γ-secretase processing to promote synaptic vesicle docking in mouse hippocampal neurons.

Synaptotagmin 7 (SYT7) has emerged as a key regulator of presynaptic function, but its localization and precise role in the synaptic vesicle cycle remain the subject of debate. Here, we used iGluSnFR to optically interrogate glutamate release, at the single-bouton level, in SYT7KO-dissociated mouse hippocampal neurons. We analyzed asynchronous release, paired-pulse facilitation, and synaptic vesicle replenishment and found that SYT7 contributes to each of these processes to different degrees. 'Zap-and-freeze' electron microscopy revealed that a loss of SYT7 diminishes docking of synaptic vesicles after a stimulus and inhibits the recovery of depleted synaptic vesicles after a stimulus train. SYT7 supports these functions from the axonal plasma membrane, where its localization and stability require both γ-secretase-mediated cleavage and palmitoylation. In summary, SYT7 is a peripheral membrane protein that controls multiple modes of synaptic vesicle (SV) exocytosis and plasticity, in part, through enhancing activity-dependent docking of SVs.

High SYT7 expression is associated with poor prognosis in human non-small cell lung carcinoma

Synaptotagmin 7 (SYT7) can encode a single-pass 46-kDa transmembrane protein which located on human chromosome 11q12.2. It has been reported to be dysregulated in several cancers; however, there are few reports on the role of SYT7 in non-small cell lung carcinoma (NSCLC). The purpose of our study was to investigate the expression of SYT7 in NSCLC and its relationship with the prognosis of NSCLC. Differences in SYT7 expression were explored by using a public database and tissue samples. The prognostic value of SYT7 and its expression correlation with clinical parameters were evaluated by statistical analysis. Our current study found that elevated mRNA and protein levels of SYT7 in NSCLC tissues compared to adjacent normal tissues. The high expression of SYT7 in NSCLC patients was positively correlated with tumour differentiation (P = 0.031) and pT (P = 0.041). The higher SYT7 expression had a shorter survival time than those with lower SYT7 expression in NSCLC patients. Furthermore, multivariate analysis demonstrated that the expression of SYT7 was an unfavourable independent prognostic factor for NSCLC (P = 0.044). In conclusion, SYT7 was upregulated in NSCLC tissues and maybe a prognostic and diagnostic factor of NSCLC.

Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner.

Synchronous neurotransmitter release is triggered by Ca2+ binding to the synaptic vesicle protein Synaptotagmin 1, while asynchronous fusion and short-term facilitation is hypothesized to be mediated by plasma membrane-localized Synaptotagmin 7 (SYT7). We generated mutations in Drosophila Syt7 to determine if it plays a conserved role as the Ca2+ sensor for these processes. Electrophysiology and quantal imaging revealed evoked release was elevated 2-fold. Syt7 mutants also had a larger pool of readily-releasable vesicles, faster recovery following stimulation, and intact facilitation. Syt1/Syt7 double mutants displayed more release than Syt1 mutants alone, indicating SYT7 does not mediate the residual asynchronous release remaining in the absence of SYT1. SYT7 localizes to an internal membrane tubular network within the peri-active zone, but does not enrich at active zones. These findings indicate the two Ca2+ sensor model of SYT1 and SYT7 mediating all phases of neurotransmitter release and facilitation is not applicable at Drosophila synapses.

Silencing of synaptotagmin 7 regulates osteosarcoma cell proliferation, apoptosis, and migration.

Synaptotagmin 7 (SYT7) is a component of the synaptotagmin family, which is essential in many physiological and pathological processes. In this study, we aimed to investigate the role of SYT7 in osteosarcoma. We defined the expression levels of SYT7 in osteosarcoma tissues and para-sarcoma tissues by immunohistochemistry and analyzed the possible correlation between SYT7 expression and pathological characteristics via Mann-Whitney U analysis and Spearman correlation analysis. The effects of SYT7 silencing in vitro cell growth were assessed by MTT assay. Cell cycle and cell apoptosis were assessed by flow cytometry analysis. Wound healing assay and transwell assay were applied to assess the migration and invasion capacity. The results showed that the expression levels of SYT7 were upregulated in osteosarcoma tissues compared with para-sarcoma tissues and positively correlated with the pathological characteristics of osteosarcoma. Functional experiments demonstrated that SYT7 silencing significantly inhibited cell proliferation and colony formation capacity (P<0.001), induced cell cycle arrest which increased the proportion of G2 phase and decreased the proportion of S phase, enhanced cell apoptosis (P<0.01), and limited the capacity of migration and invasion (P<0.01), compared with shCtrl group. The results indicated that SYT7 plays a crucial role in the development of osteosarcoma. SYT7 can be applied as a new diagnostic and therapeutic target in osteosarcoma.

Synaptotagmin 7 in twist-related protein 1-mediated epithelial – Mesenchymal transition of non-small cell lung cancer

BackgroundTwist-related protein 1 (TWIST1) plays an essential role in the carcinogenesis and metastasis of NSCLC. Our aims were to identify the molecule at the downstream of TWIST1 and to evaluate its potential as a diagnostic and a prognostic marker in NSCLC. MethodsThe functional genes at the downstream of TWIST1 were obtained via microarray gene expression analyses in the NSCLC cell line. The expression levels of synaptotagmin 7 (SYT7) in a cohort of patients with NSCLC (n = 154) were examined using immunohistochemistry staining and assessed by Kaplan-Meier survival analysis and Cox regression analysis. The effects of SYT7 on the tumorigenesis and metastasis of NSCLC were measured in NSCLC cells. In vivo xenograft lung cancer models were used to study the tumorigenesis role of SYT7. FindingsWe discovered that SYT7 is significantly altered by TWIST1 expression. We further confirmed that SYT7 protein was significantly higher in NSCLC than that in the adjacent normal lung tissue, and higher SYT7 expression was associated with poor survival of NSCLC patients. The protein level of SYT7 was positively correlated with TWIST1 in NSCLC tissue. Functional experiments indicated that SYT7 promoted proliferation, invasion, and metastasis and inhibited cell apoptosis of NSCLC cells in vitro. In vivo experiments showed that shSYT7 inhibited the xenograft tumor growth of NSCLC cells. Knocking down of SYT7 increased the expression of E-cadherin and decreased the level of N-cadherin and Vimentin in cultured cells. InterpretationOur data indicate that SYT7 is an important promoter for EMT and tumor progression in NSCLC. FundThis project was supported by grants from the Major Scientific and Technological Innovation Project of Shandong Province (2018CXGC1212), Science and Technology Foundation of Shandong Province (2014GSF118084, 2016GSF121043), Medical and Health Technology Innovation Plan of Jinan City (201805002) and the National Natural Science Foundation of China (81372333).

Identification of Genetic Loci Associated with Plasma Long-chain Polyunsaturated Fatty Acids in Hispanic Children (P08-129-19)

ObjectivesLong-chain polyunsaturated fatty acids (LC-PUFAs) are critical to the functioning of cell membranes as important constituents of phospholipids. They also serve as precursors for prostaglandins, leukotrienes and thromboxanes which affect metabolic processes such as vasodilation, inflammation and cell proliferation. The objective of this study was to identify genes that influence the plasma levels of LC-PUFAs in Hispanic children of the Viva La Familia study. MethodsPlasma levels of LC-PUFAs, including eicosapentanoic acid (EPA, 20:5, n-3), docosahexanoic acid (DHA, 22:6, n-3), docosapentanoic acid (DPA, 22:5, n-3), arachidonic acid (20: 4 n-6) and docosapentanoic acid (DPA, 22:5 n-6), were measured as part of metabolomics profiling. Genome-wide single nucleotide polymorphisms (SNP) (array and exome sequence) association analysis (GWAS) were conducted using additive genetic models adjusting for kinships. ResultsGWAS identified several loci on chromosome 11 with significant evidence of association with LC-PUFAs. These include association of EPA and arachidonic acid with rs174548, rs174545, rs174546, rs174550, 1rs74538 of fatty acid desaturase 1 (FADS1), rs1535, rs174577, rs174568, 174570, 2072114, 2727270 of FADS2, rs174538 of flap structure-specific endonuclease 1 (FEN1), rs174535, rs174528, rs198462, rs174532, rs149803 and rs198464 of myelin regulatory factor (MYRF) and rs102275 and rs102274 of transmembrane protein 258 (TMEM258) (P < 10−12, MAF 5–45%). Other LC-PUFAs showed suggestive evidence of association with the same SNPs. Except for FADS2 SNPs, carriers of minor alleles of all other identified SNPs had lower levels of EPA and arachidonic acid with effect sizes ranging from 5–10%. The analysis of exome variants revealed significant association of EPA with two novel SNPs in syphingomyelin synthase 2 (SGMS2) (P = 1.6 × 10−8) and synaptotagmin 7 (SYT7) (<3 × 10−15, MAF 1.5–33%). The same two loci were associated with arachidonic acid (<6 × 10−9). No significant or suggestive associations were found for other LC-PUFAs. ConclusionsIn summary, our genome-wide and exome sequencing results replicated the association of EPA and arachidonic acid with FADS and TMEM258 genes and identified novel loci related to neuronal signaling mainly in MYRF, SGMS2 and SYT7. Funding SourcesNational Institutes of Health (NIH) [DK080457], and the USDA/ARS [Cooperative Agreement 6250-51000-053].

Synaptotagmin-7, a binding protein of P53, inhibits the senescence and promotes the tumorigenicity of lung cancer cells.

Lung cancer has been one of the most common malignancies in the world. Cell senescence has been recognized as the avenue to inhibit tumor progression. However, the mechanisms remain poorly understood. In the present study, we have shown that synaptotagmin-7 (SYT7) expression was up-regulated in lung cancer. SYT7 also promoted the growth and colony formation of lung cancer cells and inhibited their senescence. In a molecular mechanism study, SYT7 was shown to interact with P53 and to potentiate the interaction between P53 and MDM2. Taken together, the present study demonstrates the oncogenic roles of SYT7 in lung cancer, and suggests that SYT7 may be a good therapeutic target for lung cancer treatment.

Synaptotagmin 7 in Twist-Related Protein 1-Mediated Epithelial-Mesenchymal Transition of Non-Small Cell Lung Cancer

Background: Twist-related protein 1 (TWIST1) plays an essential role in the carcinogenesis and metastasis of NSCLC. Our aims were to identify a novel molecule at the downstream of TWIST1 that mediates metastasis of NSCLC, and to evaluate its potential as a diagnosis and a prognosis marker. Methods: The functional genes associated with invasion and metastasis at the downstream of TWIST1 were obtained by microarray gene expression analyses in NSCLC cell line. The expression levels of Synaptotagmin 7 (SYT7) in a cohort of patients with NSCLC (n=154) were examined by immunohistochemistry staining, and assessed by Kaplan-Meier survival analysis and Cox regression analysis. The effects of SYT7 on tumorgenesis and metastasis of NSCLC were measured in vitro and in vivo. Findings: We first discovered that SYT7 is significantly altered by TWIST1 expression in microarray gene expression analyses. We further confirmed that SYT7 protein was significantly higher in NSCLC tissues than that in the adjacent normal lung tissues, and higher SYT7 protein expression was associated with poor survival of NSCLC patients. Functional experiments indicated that SYT7 promotes proliferation, invasion and metastasis, and inhibits cell apoptosis of NSCLC cells in vitro and in vivo. We demonstrated that knocking down SYT7 increases expression of E-cadherin and decreases the level of N-cadherin and Vimentin of cultured cells, indicating an involvement of EMT by SYT7. Interpretation: Our data indicate that SYT7 is an important promoter for EMT and tumor progression in NSCLC. Funding: This project was supported by grants from the Major Scientific and Technological Innovation Project of Shandong Province (2018CXGC1212), Science and Technology Foundation of Shandong Province (2014GSF118084, 2016GSF121043), Medical and Health Technology Innovation Plan of Jinan City (201805002) and the National Natural Science Foundation of China (81372333). Declaration of Interest: No potential conflicts of interest were disclosed. Ethical Approval: This study was conducted with the approval of the ethical committees of Qilu Hospital of Shandong University (Jinan, China).

Synaptotagmin7 Is Overexpressed In Colorectal Cancer And Regulates Colorectal Cancer Cell Proliferation.

Purpose: Synaptotagmin7 (SYT7) belongs to the synaptotagmin gene family and plays an important role in synaptic transmission. However, the function of this gene in most human cancer especially in colorectal cancer (CRC) remains unknown. In this research, we examined SYT7's role in CRC and tried to reveal its underlying mechanism.Methods: We examined SYT7's expression levels in normal colorectal tissue and CRC tissues from 83 patients and analyzed the possible correlation between the expression level of SYT7 and pathological characteristics. The influences of SYT7 knockdown on cell growth were detected by Celigo image cytometer, colony formation assay, cell cycle analysis and apoptosis assay in vitro. The possible molecular mechanism was assessed using a microarray and Ingenuity Pathway Analysis.Results: Our results show that the expression of SYT7 is upregulated in colorectal cancer tissues in comparison with normal tissues and positively correlated with the pathological stage of colorectal cancer. (P=0.015). We examined SYT7's role in human colorectal cancer cell line RKO by using SYT7-shRNA and revealed that SYT7 knockdown inhibit cell proliferation (P=8.6E-5), clonogenic ability (P=4.5E-6) and promoted G2/M Phase arrest and apoptosis (P=4.6E-7). Multiple cancer-associated pathways regulated by SYT7 were unraveled by microarray and Ingenuity Pathway Analysis.Conclusions: Our study suggests that SYT7 plays an important role in the development of CRC and SYT7 may become a new therapeutic target in CRC.

Downregulation of SYT7 inhibits glioblastoma growth by promoting cellular apoptosis.

Synaptotagmin‑7 (SYT7) is a member of the synaptotagmin gene family, and encodes a protein that mediates the calcium‑dependent regulation of membrane trafficking during synaptic transmission. A previous study demonstrated that the expression of SYT7 is associated with prostate cancer and serves an important role in development of prostate cancer. However, the roles of SYT7 in the progression of glioma remain unknown. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis demonstrated that SYT7 was expressed in three human glioma cell lines. Western blotting and RT‑qPCR analysis demonstrated the knockdown efficiency of SYT7 shRNA in 293Tcells and U87MG cells. Celigo Image Cytometer Analysis, a caspase‑3/7 assay, flow cytometry and an MTT assay demonstrated that the proliferation of U87MG cells was inhibited as SYT7 was downregulated by a lentiviral vector expressing SYT7 shRNA, via the promotion of cellular apoptosis. The results of the present study demonstrated that the downregulation of SYT7 inhibited glioblastoma growth by promoting cellular apoptosis, and that SYT7 may therefore be a potential target for glioma intervention.

Synaptotagmin 7 and SYNCRIP proteins are ubiquitously expressed in the rat brain and co-localize in Purkinje neurons

Synaptotagmin 7 (SYT7) is ubiquitously expressed calcium sensor, involved in neuronal membrane trafficking. Immunoprecipitation experiments demonstrated that SYT7 interacts with Synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP). SYNCRIP is a component of mRNA granules, which are transported to dendrites and are prerequisite for synaptic plasticity. Given the potential significance of SYT7 regulation in processes of neurodegeneration, which are characterized by high level of synaptic vulnerability, we aimed to analyse and compare the distribution of SYT7 and SYNCRIP proteins in the adult rat striatum, hippocampus, cerebral and cerebellar cortex. We investigated the degree of SYT7-SYNCRIP co-localization in order to examine possible functional interaction of these two proteins. We found that SYT7 is abundantly distributed in neuropil of all examined anatomical areas of the brain, most prominently in axons. On the contrary, SYNCRIP had cytoplasmic somatodendritic pattern of expression, which was most prominent in the hippocampus and cerebellum. In the striatum, hippocampus and cerebral cortex SYT7 and SYNCRIP immunofluorescent signals were mutually excluded, thus diminishing the probability for their physiological interaction. In somata of Purkinje neurons in the cerebellar cortex, both SYT7 and SYNCRIP were expressed and partially co-localized suggesting possible functional connection between SYT7 and SYNCRIP proteins in Purkinje neurons.