ABSTRACT
BACKGROUND: Rab37 encodes a Rab GTPase which regulates the vesicular transport of exocytosis. But the different findings in two types of cancers made its roles in oncology more confused. In this study, a clinical research on genetic polymorphisms was performed to evaluate the association between Rab37 and esophageal squamous cell carcinoma (ESCC). METHODS: The mRNA expression was tested by reverse transcription-polymerase chain reaction (RT-PCR) in four ESCC cell lines. A case-control study including 212 ESCC patients and 213 cancer-free controls was genotyped by PCR-restriction fragment length polymorphism. The Hardy-Weinberg equilibrium test, association analysis and haplotype analysis were performed with SPSS and SHEsis software respectively. RESULTS: Rab37 mRNA could be specifically detected in two ESCC cell lines, EC109 and EC9706, but not in KYS150 and KYS450. The allele, genotype and haplotype frequencies of rs9904078G>A, rs2034310T>C and rs5018106T>C, located in Rab37, did not significantly differ between the patients and the controls. No association between the polymorphisms and the TNM stages of patients was found. CONCLUSIONS: Rab37 mRNA was specifically expressed in some ESCC cell lines but its genetic polymorphisms were not associated with ESCC.
Subject(s)
Carcinoma, Squamous Cell/genetics , Esophageal Neoplasms/genetics , Genetic Association Studies , rab GTP-Binding Proteins/genetics , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Cell Line, Tumor , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Staging , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers worldwide. However, the etiology is complex and unclear. 3q26 harboring abundant oncogenes have been identified as the loci of ESCC susceptibility. In the present study, we examined whether CNVs on 3q26 would be associated with the risk, TNM stage and prognosis of ESCC. METHODS: Variation_91720 in phosphatidylinositol 3-kinase catalytic subunit (PIK3CA) and Variation_91733 in sex-determining region Y-box 2 overlapping transcript (SOX2OT) were selected for investigation. The study included 204 ESCC patients and 208 healthy controls. The copy number of the selected sites and mRNA was detected by real-time fluorescence quantitative polymerase chain reaction and calculated using the CopyCaller v2.0 software program. RESULTS: The copy number distribution of Variation_91720 was significantly different in ESCC cases and matched controls (p<0.001). Copy number loss of Variation_91720 may increase the risk of ESCC (OR=6.217, 95% CI=3.117-12.400; adjusted OR =6.251, 95% CI=3.130-12.428). PIK3CA mRNA expression was higher in tumor tissue (P=0.0003) and increased with the copy number gain of Variation_91720. CONCLUSION: Our findings suggest that copy number loss of Variation_91720 in PIK3CA predicts risk of ESCC, which might serve as a biomarker that for early diagnosis of ESCC.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , DNA Copy Number Variations , Esophageal Neoplasms/genetics , Gene Dosage , Phosphatidylinositol 3-Kinases/genetics , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Class I Phosphatidylinositol 3-Kinases , Early Detection of Cancer , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma , Female , Fluorescence , Gene Expression Regulation, Neoplastic , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Phenotype , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Risk Factors , Software , Time FactorsABSTRACT
SCOPE: Adult hippocampal neurogenesis is a lifelong feature of brain plasticity that appears to be critically involved in adult brain function and neurological disease. Recent studies suggest that (-)-epigallocatechin-3-gallate (EGCG), which is the main polyphenolic constituent of green tea, may be used for the prevention and treatment of various neurodegenerative diseases. We hypothesized that EGCG promotes adult neurogenesis, which may be beneficial to hippocampus-dependent learning and memory. METHODS AND RESULTS: We show that EGCG treatment significantly increased the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in adult hippocampal neural progenitor cell (NPC) cultures and in the dentate gyrus of adult mice. Meanwhile, EGCG markedly improved spatial cognition in mice. These events are associated with the sonic hedgehog (Shh) signaling pathway. We observed that EGCG triggered a robust upregulation of Shh receptor (Patched) mRNA and protein expression in cultured NPCs as well as an upregulation of the downstream Shh transcriptional target Gli1. These changes were further confirmed in the hippocampus of mice administered EGCG. The blockage of the Shh signal with the pharmacological inhibitor cyclopamine attenuated EGCG-induced hippocampal neurogenesis. CONCLUSION: Our results provide strong evidence that EGCG enhances adult hippocampal neurogenesis.