RESUMO
OBJECTIVE: The aim of this study was to investigate the function of FAL1 in gastric cancer (GC) development and to examine its underlying mechanism. Our study might provide a theoretical basis for developing novel diagnostic markers for GC. PATIENTS AND METHODS: FAL1 expression in GC tissues and adjacent tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The serum level of FAL1 in GC patients with different pathological grades was further detected. The effects of FAL1 on cell proliferation and cell cycle were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Meanwhile, Western blot was used to detect the protein expression of PTEN after FAL1 overexpression or knockdown in GC cells. In addition, rescue experiments were conducted to verify the regulatory effect of FAL1 on PTEN. RESULTS: QRT-PCR results showed that the expression of FAL1 in GC tissues was remarkably higher than that of adjacent tissues. FAL1 expression was correlated with pathological grades of GC patients. Meanwhile, FAL1 overexpression promoted the proliferation and cell cycle of BGC-823 and MGC-803 cells. Western blot analysis demonstrated that FAL1 could inhibit the protein expression of PTEN in GC cells. In addition, rescue experiments indicated that the overexpression of PTEN could partially reverse the effect of FAL1 on the proliferation and cell cycle of BGC-823 and MGC-803 cells. CONCLUSIONS: The overexpression of FAL1 can promote cell proliferation and cell cycle of GC via inhibiting PTEN.
Assuntos
Proliferação de Células , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/enzimologia , Ciclo Celular , Linhagem Celular Tumoral , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Gradação de Tumores , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Three-dimensional (3D) cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC) spheroids were made by solid freeform fabrication (SFF) from the solution of poly(D,L-lactide-co-glycolide). Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.