Abstract
Purpose The aim of this study was to investigate the role of Visinin Like 1 (VSNL1) in the proliferation and migration of gastric cancer (GC) cells as well as its clinical prognostic significance. Methods To this end, we evaluated VSNL1 expression in GC tissues and cell lines by real-time PCR and immunohistochemistry. To further explore the effects of VSNL1, a lentiviral vector expressing a short hairpin RNA (shRNA) against VSNL1 was constructed and transduced into the GC cell lines BGC-823 and SGC-7901. The interference efficiency of VSNL1-shRNA was determined by western blot. The effects of VSNL1 on the migration and invasion of GC cells as well as the expression of P2X3/P2Y2 were explored using MTS, colony formation, migration, and western blot assays. Results VSNL1 mRNA and protein levels were increased in GC tissues and cell lines. Furthermore, VSNL1 expression was positively correlated with Lauren's classification, lymph node metastasis, distant metastasis, TNM stage, and prognosis. VSNL1 expression was inversely correlated with the 5-year survival rate of GC patients. VSNL1 expression was markedly reduced in cells transduced with lentivirus expressing shRNA against VSNL1, and inhibiting VSNL1 expression significantly suppressed cell growth, migration, and colony formation and reduced the expression of P2X3/P2Y2. Conclusion VSNL1 may promote the proliferation and migration of GC cells by regulating P2X3 and P2Y2 expression. VSNL1 plays important roles in GC development and metastasis and may be correlated with patient prognosis.
Highlights
Visinin Like 1 (VSNL1; known as VILIP-1) is a member of the neuronal calcium sensor protein family and regulates calcium-dependent cellular signaling and signal transduction by modulating adenylate cyclase [1]
Our study showed that VSNL1 was more highly expressed in gastric cancer (GC) cells and tissue and that VSNL1 expression was significantly correlated with lymph node and distant metastases and TNM stage
VSNL1 was found to be overexpressed in neuroblastoma specimens from patients with distant metastases [5]
Summary
Visinin Like 1 (VSNL1; known as VILIP-1) is a member of the neuronal calcium sensor protein family and regulates calcium-dependent cellular signaling and signal transduction by modulating adenylate cyclase [1]. The majority of current studies on VSNL1 have focused on Alzheimer’s disease and acute encephalopathy [2, 3]; VSNL1 is overexpressed in squamous cell carcinoma, neuroblastoma, non-small-cell lung cancer, colorectal cancer, and other tumor types, where it is involved in tumor invasion and metastasis [4,5,6,7]. Recent studies have shown that P2X/P2Y signaling plays important roles in inflammatory responses, metabolism, and cancer [8, 9]. Interactions between the amino terminus of VSNL1 and the carboxyl terminus of the P2X3 receptor are critical for P2X3 surface expression and functional enhancement. VSNL1 overexpression increases the expression of P2X3 receptors and enhances the excitability of naïve rat dorsal root ganglion (DRG) neurons [10].
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