RESUMO
PURPOSE: To explore FGF1 and miR-143-3p expression in hepatocellular carcinoma (HCC) cells and its related mechanisms. METHODS: Eighty-two HCC patients treated at our hospital from January 2018 to January 2019 were enrolled as Group A, while further 80 healthy people undergoing physical examinations during the same time period were enrolled as Group B. HCC cells and normal human liver cells were purchased, with HepG2 and SMMC-7721 cells transfected with pcDNA3.1-FGF1, si-FGF1, NC, miR-143-3p-inhibitor and miR-143-3p-mimics. FGF1 and miR-143-3p expression was detected by qRT-PCR. The expression of N-cadherin, vimentin, Snail, Slug, E-cadherin and γ-catenin was detected by Western Blotting (WB). Cell proliferation was detected by MTT assay. Cell invasion was detected by Transwell. Cell apoptosis was detected by flow cytometry (FCM). RESULTS: FGF1 was highly expressed but miR-143-3p was poorly expressed in HCC cells. Areas under the curves (AUCs) of the two indicators were > 0.8. The indicators were correlated with the age, gender, tumor invasion, degree of differentiation, tumor location and TNM staging of the patients. Silencing FGF1 and overexpressing miR-143-3p could promote cell apoptosis, inhibit cell growth, cell epithelial-mesenchymal transition (EMT) and the expression of N-cadherin, vimentin, Snail and Slug, and increase the expression of E-cadherin and γ-catenin. Dual luciferase reporter gene assay (DLRGA) confirmed that FGF1 and miR-143-3p had a targeted relationship. The rescue experiment showed that the proliferation, invasion and apoptosis of HepG2 and SMMC-7721 cells in the miR-143-3p-mimics+pcDNA3.1-FGF1 and miR-143-3p-inhibitor+Si-FGF1 groups were not different from those in the miR-NC group. CONCLUSION: Inhibiting FGF1 can upregulate miR-143-3p-mediated Hedgehog signaling pathway, and affect cells' EMT, proliferation and invasion, so FGF1 is expected to become a potential therapeutic target for HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Fator 1 de Crescimento de Fibroblastos/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Fatores Etários , Apoptose , Área Sob a Curva , Caderinas/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Fator 1 de Crescimento de Fibroblastos/genética , Citometria de Fluxo , Inativação Gênica , Humanos , Fígado/citologia , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Invasividade Neoplásica , Sondas RNA , Fatores Sexuais , Fatores de Transcrição da Família Snail/metabolismo , Vimentina/metabolismo , gama Catenina/metabolismoRESUMO
The A-20C polymorphism in the angiotensinogen (AGT) gene has been associated with increased risk of essential hypertension in several studies; however, these studies gave inconsistent results. In this study, we performed a meta-analysis to assess the association between AGT A-20C polymorphism and essential hypertension. Published literature was retrieved from PubMed. Pooled odd's ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effect models. A total of 10 case-control studies containing 3653 cases and 3457 controls were enrolled to this meta-analysis. In a combined analysis, the results showed a significant association between the AGT A-20C polymorphism and risk of essential hypertension (AA vs CC: OR = 0.62, 95%CI = 0.46-0.84; recessive model: OR = 0.66, 95%CI = 0.49-0.88). In the subgroup analysis stratified by race, significant associations were found between the AGT A-20C polymorphism and essential hypertension risk in Asians (AA vs CC: OR = 0.59, 95%CI = 0.43-0.80; recessive model: OR = 0.63, 95%CI = 0.46-0.85). In conclusion, the results of this meta-analysis suggested that the AGT A-20C polymorphism was associated with risk of essential hypertension in Asians.
Assuntos
Angiotensinogênio/genética , Hipertensão/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático , Hipertensão Essencial , Predisposição Genética para Doença/genética , Humanos , Razão de ChancesRESUMO
Epidemiological studies have indicated that folate metabolism is correlated with increased risk of gastric cancer. Since methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, in this study, we examined whether polymorphisms and haplotypes of MTHFR are correlated with the risk of gastric cancer. The polymorphisms MTHFR C677T and MTHFR A1298C were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 285 patients and 570 healthy controls. Association analyses based on binary logistic regression were conducted to determine the odds ratio (OR) and its 95% confidence interval (95%CI) for each genotype. The MTHFR 677TT genotype was significantly related with a reduced risk of gastric cancer (OR = 0.60, 95%CI = 0.39-0.92) compared to the CC genotype. Similarly, the MTHFR 1298CC genotype was significantly associated with a decreased risk of cancer (OR = 0.52, 95%CI = 0.32- 0.81). Haplotype analysis showed that the TC haplotype was associated with a reduced risk of gastric cancer compared to the most common haplotype, CA (OR = 0.28, 95%CI = 0.12-0.60). Our results suggest that the MTHFR C677T and MTHFR A1298C polymorphisms are related to gastric cancer susceptibility in the Chinese population.