RESUMO
Differential level and regulatory effect of circNR3C1 in gastric cancer (GC) were determined. The differential levels of circNR3C1 in clinical samples of GC were determined. The association of circNR3C1 level with pathological indicators of GC was analyzed. After intervening circNR3C1 levels in gastric cancer cells, proliferative and migratory changes were investigated. Furthermore, we measured AKT and mTOR protein levels in GC cells intervened by circNR3C1. Finally, the role of AKT/mTOR in GC cell phenotypes regulated by circNR3C1 was explored. circNR3C1 was markedly lowly expressed in GC cells and tissues. A low level of circNR3C1 predicted high incidences of lymphatic or distant metastasis of GC. Knockdown of circNR3C1 enhanced proliferation and migration abilities in BGC-823 cells, whereas overexpression of circNR3C1 yielded the opposite results in AGS cells. circNR3C1 downregulated mTOR and AKT in GC cells. In addition, induction of the AKT activator could reverse the attenuated proliferative and migratory potentials in GC cells overexpressing circNR3C1. On the contrary, induction of the AKT inhibitor reversed the stimulated malignant phenotypes of GC with circNR3C1 knockdown. circNR3C1 inhibits GC to proliferate and migrate by inactivating the AKT/mTOR signaling. It is also closely linked to GC metastasis.
Assuntos
RNA Circular/metabolismo , Receptores de Glucocorticoides/genética , Neoplasias Gástricas , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
@#[摘 要] 目的：探讨lncRNA-Z38对胃癌细胞恶性生物学行为的影响及其可能的调控机制。方法：构建lncRNA-Z38稳定过表达的胃癌细胞系（AGS、MKN74细胞），通过细胞成球实验检测过表达lncRNA-Z38对胃癌细胞肿瘤特征的影响。对过表达lncRNA-Z38的AGS细胞及对照细胞进行高通量测序，对差异表达基因进行KEGG富集分析，筛选出可能参与调控胃癌发生发展的信号通路，采用WB等技术验证lncRNA-Z38通过调控该信号通路参与提高胃癌细胞的干性。结果：成功构建lncRNA-Z38过表达细胞株，细胞成球实验提示lncRNA-Z38过表达细胞的成球能力显著高于对照细胞（P<0.05）。通过测序筛选出lncRNA-Z38过表达胃癌细胞中的1 999个差异表达基因，其中上调基因1 238个、下调基因761个；经KEGG富集分析得到其中变化最显著的通路为TGF-β信号通路（P<0.05）。WB实验结果提示，lncRNA-Z38高表达胃癌细胞中TGF-β信号通路组成基因编码蛋白ID3、BMP6显著上调（均P<0.05）、GDF-5、WNT8B显著下调（P<0.05）。结论：在胃癌中高度表达的lncRNA-Z38通过调控TGF-β信号通路提高胃癌细胞的干性。
