Knockdown of long noncoding RNA GHET1 inhibits cell-cycle progression and invasion of gastric cancer cells

摘要

GHET1 is an oncogenic long noncoding RNA (lncRNA) that promotes the proliferation and invasion of many malignant cell types. However, the function and underlying mechanisms of lncRNA GHET1 in gastric cancer are not fully understood. In this study, the expression of GHET1 was investigated in gastric cancer and it was determined whether GHET1 may potentially be used as a biomarker for the disease. The gastric cancer cell lines MGC-803 and AGS were transfected with GHET1-directed small interfering RNA (siRNA) and the changes in phenotype and cell-cycle-related molecules were assessed. The downregulation of GHET1 induced G0/G1-phase arrest in gastric cancer cells and inhibited their proliferation, migration, and invasion. DNA synthesis and the expression of proliferating cell nuclear antigen (PCNA) decreased, which was consistent with the results of the CCK-8 assay. The levels of specific cell-cycle regulators were determined and the expression and activities of positive cell-cycle regulators (cyclin D, CDK4, CDK6, cyclin E, CDK2) were reduced, whereas those of a negative regulator (P21) were increased in GHET1-knockdown cells. Taken together, the present findings show that the downregulation of GHET1 not only inhibits the migration and invasion of gastric cancer cells, but also inhibits their proliferation, at least in part by upregulating P21 expression and downregulating cyclin and CDK expression to inhibit the G0/G1 to S phase transition. The present findings may provide a potential therapeutic target for gastric cancer.