RESUMO
Mini-chromosome maintenance (MCM) proteins play important roles in initiating eukaryotic genome replication. The MCM family of proteins includes several members associated with the development and progression of certain cancers. We performed online data mining to assess the expression of MCMs in gastric cancer (GC) and the correlation between their expression and survival in patients with GC. Notably, MCM8 expression was undoubtedly up-regulated in GC, and higher expression correlated with shorter overall survival (OS) and progression-free survival (PFS) in patients with GC. However, the role of MCM8 in GC has not been previously explored. Our in vitro experiments revealed that MCM8 knockdown inhibited cell growth and metastasis. Moreover, MCM8 knockdown induced apoptosis. Mechanistically, the expression levels of Bax and cleaved caspase-3 were increased, whereas Bcl-2 expression decreased. Additionally, we demonstrated that MCM8 knockdown suppressed tumorigenesis in vivo. Overall, these results suggest that MCM8 plays a significant role in GC progression.
Assuntos
Apoptose/genética , Biomarcadores Tumorais , Proteínas de Manutenção de Minicromossomo/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Animais , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Proteínas de Manutenção de Minicromossomo/metabolismo , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Análise de SobrevidaRESUMO
Qingjie Fuzheng granule (QFG) promotes cancer cell apoptosis and ameliorates intestinal mucosal damage caused by 5-fluorouracil. However, the antitumor role of QFG in colorectal cancer (CRC) progression remains unclear. In this study, the growth of HCT-8 and HCT116 cells incubated with various concentrations of QFG for 24 and 48 h was evaluated using MTT assays; their abilities of migration and invasion were investigated through wound healing and Transwell assays. The expression of lncRNA ANRIL, let-7a, and the TGF-ß1/Smad signaling pathway components was assessed using real-time PCR and western blotting. The results elicited that QFG significantly suppressed the growth of HCT-8 and HCT116 cells; the half-maximal inhibitory concentrations (IC50) of QFG for HCT-8 and HCT116 cells for 48 h were 1.849 and 1.608 mg/mL, respectively. The abilities of wound healing, migration, and invasion of HCT-8 and HCT116 cells were dose-dependently decreased by QFG treatment for 24 h, respectively. QFG decreased the expression of lncRNA ANRIL, TGF-ß1, phosphorylated (p)-Smad2/3, Smad4, and N-cadherin and upregulated the expression of let-7a in HCT-8 and HCT116 cells. Collectively, our data demonstrated that QFG inhibited the metastasis of CRC cells by regulating the lncRNA ANRIL/let-7a/TGF-ß1/Smad axis, indicating that they might serve as an adjunctive medicine for CRC treatment.
