ABSTRACT
The aim of this study was to investigate the expression of miR-21 in esophageal cancer and the impact of miR-21 on apoptosis, invasion, and the expression of target genes in esophageal cancer cells. Fluorescence quantitative polymerase chain reaction analysis was used to detect the expression of miR-21 in human esophageal tissues, adjacent tissues, and an esophageal cancer cell line (TE-13). The antisense miR-21 oligonucleotide was generated commercially using the solid-phase chemical synthesis method. Transient transfection was used to transfect esophageal cancer cells (TE-13 antisense and TE-13 control cells). Flow cytometry and Transwell cell assays were used to detect the apoptosis and invasion of esophageal cancer cells, respectively. The western blot method was used to detect the expression of PTEN, PDCD4, and K-ras proteins. These analyses determined that mir-21 expression significantly increased in esophageal cancer tissues and in TE-13 cells, and that this phenomenon was not associated with staging or lymph node metastasis. The apoptosis rate of TE-13 control cells was lower than that of antisense TE-13 cells indicating an enhanced invasive ability. In tissues adjacent to esophageal cancer and in TE-13 antisense cells, the expression of PTEN and PDCD4 was found to be higher than that in the control group, whereas the expression of K-ras showed the opposite pattern. Together, these results suggest that miR- 21 might be involved in the development and metastasis of esophageal cancer, through interaction with its PDCD4 and K-ras target genes.
Subject(s)
Carcinoma, Squamous Cell/genetics , Esophageal Neoplasms/genetics , MicroRNAs/biosynthesis , Aged , Apoptosis/genetics , Apoptosis Regulatory Proteins/biosynthesis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Female , Humans , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Invasiveness , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides, Antisense/genetics , PTEN Phosphohydrolase/biosynthesis , RNA-Binding Proteins/biosynthesis , Transfection , ras Proteins/biosynthesisABSTRACT
The present study aimed to explore the relationship between miRNA expression and survival in patients with esophageal cancer (EC) using meta-analysis. We searched PubMed, EMBASE, CNKI, Wanfang, and ISI Web of Science databases without time restrictions, and extracted relevant data, such as the name of first author, publication year, age, gender, number of case, etc. from the studies included. We calculated the pooled hazard ratios (HRs) using the RevMan 5.2 software. A total of five studies involving 504 subjects were included in the meta-analysis, with the purpose of analyzing the association of miRNA-21 expression with EC prognosis. The pooled HR of elevated versus decreased miR-21 expression in EC was 1.87 [95% confidence interval (CI): 1.37-2.55, P < 0.001], with elevated miR-21 expression being associated with poorer prognosis for patients with EC. Our results support a prognostic role for miR-21 in EC.
Subject(s)
Esophageal Neoplasms/genetics , MicroRNAs/biosynthesis , Prognosis , Databases, Factual , Esophageal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , PubMed , SoftwareABSTRACT
We conducted a comprehensive study to investigate the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. Genotyping of seven gene polymorphisms was performed on a 384-well plate format on the Sequenom MassARRAY platform in 162 patients with osteosarcoma. We studied the correlation of the seven gene polymorphisms with response to chemotherapy and clinical outcome of patients. Individuals with the ABCB1 TT genotype had a higher probability of responding poorly to chemotherapy, indicated by an odds ratio (OR) of 2.64 (95%CI=1.04-6.83). Similarly, the genotype of GSTP1 GG was significantly associated with improved responses to chemotherapy, indicated by an OR of 3.33 (95%CI=1.26-8.99). The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter overall survival (OS). Our study found that two gene polymorphisms in two transporter genes and one Phase II metabolism enzymes are associated with response to chemotherapy and OS in osteosarcoma patients, suggesting the potential of the two gene polymorphisms as prognostic biomarkers for osteosarcoma.
Subject(s)
Bone Neoplasms/genetics , Glutathione S-Transferase pi/genetics , Osteosarcoma/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Adolescent , Adult , Biomarkers, Pharmacological , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Child , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Humans , Male , Metabolic Detoxication, Phase II/genetics , Middle Aged , Osteosarcoma/drug therapy , Osteosarcoma/pathology , Polymorphism, Single Nucleotide , PrognosisABSTRACT
Metallothionein (MT)-3 has cell growth inhibitory activity, and is the only currently known MT subtype with unique physiological functions. The expression levels of MT-1E, a subtype of MT-1, were positively correlated with the degree of esophageal cancer malignancy. The present study aimed to investigate the effects of MT-3 and MT-1E gene transfection on the proliferation, cell cycle, and apoptosis of esophageal cancer cells. The cationic liposome method was used to transfect the esophageal cancer strains Eca-109 and TE13. Reverse transcription-polymerase chain reaction was used to detect target gene expression, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction was applied to detect cell proliferation, and flow cytometry was used for cell cycle and apoptosis detection. Esophageal cancer cells with MT-3 and MT-1E gene transfection showed high expression of the foreign target gene and mRNA. Cells with MT-3 gene transfection showed markedly inhibited proliferation (P < 0.05), a significantly higher proportion of cells in the G0/G1 phase (P < 0.05), a significantly lower proportion of cells in the S phase (P < 0.05), and a significantly increased apoptosis rate (P < 0.05). Cells with MT-1E gene transfection did not show significant changes in proliferation, cell cycle, or apoptosis rate (P > 0.05). Therefore, the upregulation of MT-3 gene expression can inhibit esophageal cancer cell proliferation and induce apoptosis, which may be achieved by blocking the tumor cell growth cycle, whereas effects of the MT-1E gene on the proliferation of esophageal cancer cells were not evident.
Subject(s)
Apoptosis , Cell Proliferation , Esophageal Neoplasms/metabolism , Metallothionein/genetics , Nerve Tissue Proteins/genetics , Cell Cycle Checkpoints , Cell Line, Tumor , Esophageal Neoplasms/pathology , Gene Expression , Humans , Metallothionein/biosynthesis , Metallothionein 3 , Nerve Tissue Proteins/biosynthesis , TransfectionABSTRACT
An A/G polymorphism (rs3746444) has been identified in the miR-499 gene that can change the conformation of the secondary gene structure and thereby directly affect binding to target mRNAs and the microRNA (miRNA) maturation process, thus altering protein expression and potentially contributing to cancer susceptibility. Numerous studies investigating the association between the rs3746444 polymorphism and cancers have been published; however, results are inconsistent and inconclusive. To clarify the relationship between the miR-499 rs3746444 polymorphism and cancer, we conducted a comprehensive meta-analysis on 14 case-control studies comprising 7189 cases and 8577 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by using dominant, recessive, and co-dominant genetic models. A publication bias test and subgroup analysis were also performed. Results showed that the G allele was associated with a significantly increased cancer risk compared to the A allele (OR = 1.09; 95%CI = 1.00-1.18). Similarly, moderately elevated risks were also observed in overall analyses in the dominant model (OR = 1.13; 95%CI = 1.01-1.26). Moreover, significantly increased risks were observed in Asian populations (G allele vs A allele: OR = 1.18; 95%CI = 1.01-1.37; GG vs AA: OR = 1.36; 95%CI = 1.07-1.73; dominant model: OR = 1.19; 95%CI = 1.00-1.41; recessive model: OR = 1.31; 95%CI = 1.03-1.66), but not in European populations. These findings indicate that the miR-499 rs3746444 polymorphism is associated with an increased cancer risk.