RESUMO
Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial-mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.
Assuntos
Transição Epitelial-Mesenquimal , MicroRNAs/metabolismo , Osteopontina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Apoptose/genética , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Camundongos Nus , MicroRNAs/genética , Modelos Biológicos , Invasividade Neoplásica , Osteopontina/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/genéticaRESUMO
The aim of this study was to investigate the expression of Nrf2 and IGF-1 in benign, premalignant, and malignant gastric lesions, and to explore the role of Nrf2 and IGF-1 in gastric carcinoma carcinogenesis. Nrf2 and IGF-1 expression was detected in normal gastric mucosa, hyperplastic polyp, intraepithelial neoplasia, and adenocarcinoma by immunohistochemistry. There was no expression of Nrf2 and IGF-1 in normal gastric mucous membrane. With the elevation of Nrf2, IGF-1 expression, their co-expressions were highly elevated from benign proliferative lesions to malignant lesions. There were significant differences between hyperplastic polyps, intraepithelial neoplasias, and adenocarcinoma (hyperplastic polys vs. intraepithelial neoplasia: P=0.012; hyperplastic polyps vs. adenocarcinoma: P=0.023; and intraepithelial neoplasia vs. adenocarcinoma: P=0.027; hyperplastic polyps vs. adenocarcinoma: P=0.0000, respectively). Nrf2 expression and IGF-1 expression were correlated positively (r=0.337, P=0.037). The increased expression of Nrf2 and IGF-1 may be related to gastric carcinogenesis. Elevated Nrf2 and IGF-1 may play important roles in promoting tumor progression.