RESUMO
OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor worldwide. Its five-year survival rate has decreased significantly in recent years. This study was aimed at exploring the roles of the IGF2BP1/UHRF2 axis and miR-98-5p in the progression of esophageal squamous cell carcinoma. METHODS: The ESCC tissues and paracancerous tissues were collected from the 40 patients with ESCC after surgical resection at the First Affiliated Hospital of Chongqing Medical University (Chongqing, China) from January 2019 to January 2020. The clinicopathological characteristics of these patients were analyzed. Gene expression in all specimens was tested to detect miR-98-5p expression. The function of miR-98-5p on ESCC cell proliferation and apoptosis was performed in vitro. The relationship between UHRF2, IGF2BP1, and miR-98-5p was analyzed by IP assay, bioinformatics methods, and Western bolt. RESULTS: The expression of miR-98-5p decreased in 32/40 (80.0%) of the ESCC patient samples. Kaplan-Meier survival analysis of the TCGA cohort grouped by miR-98-5p levels produced significant differences in overall survival (log rank p=0.027). miR-98-5p suppressed ESCC progression. IGF2BP1 and UHRF2 promoted ESCC invasion and proliferation, and they inhibited apoptosis through miR-98-5p mediation. CONCLUSION: miR-98-5p and the IGF2BP1/UHRF2 axis might have the biological functions of regulating cell proliferation and apoptosis in the progression of ESCC, which might provide potential novel targets, such as miR-98-5p, in the treatment of esophageal squamous cell carcinoma.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas de Ligação a RNA/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/genéticaRESUMO
OBJECTIVE: To study the effect of valproate acid sodium(VPA) on apoptosis of human gastric cancer cell BGC-823 and to explore its possible mechanism. METHODS: Cell growth inhibition was examined by MTT assay. Apoptosis rate was detected by FCM with Annexin V/PI staining. The activities and protein expression levels of caspase 3, caspase 8 and caspase 9 were examined by spectrophotometry and indirect immunofluorescence technique respectively. RESULTS: The growth inhibition rate and apoptosis rate of human gastric cancer cells, treated with 0.75-4.00 mmol/L VPA for 24 h and 48 h, elevated in time- and dose-dependent manner. Apoptosis rates of VPA 0.75 mmol/L 24 h and 48 h were (7.2 +/- 0.5)% and (9.2 +/- 1.0)%, of VPA 4.00 mmol/L 24 h and 48 h were (16.7 +/- 2.2)% and (20.4 +/- 1.6)% respectively, which were significantly different as compared to the control [24 h, (4.9 +/- 0.2)%, 48 h, (5.1 +/- 0.8)%] (P< 0.001). The activities and protein expression levels of caspase 3 and caspase 9 were up-regulated compared with the control group (P< 0.001), meanwhile the activity and protein expression of caspase 8 enhanced slightly after VPA treatment for 48 h. CONCLUSION: VPA can inhibit the growth and induce the apoptosis of BGC-823 cells mainly through the activation of caspase 9 pathway.
