Purpose: Long non-coding RNAs (lncRNAs) play critical regulatory roles in the tumorigenesis of GC. This study aimed to investigate the regulatory effect and mechanism of lncRNA-HCG18 on GC.
Methods: The expression of lncRNA-HCG18 was detected in GC tissues and cell lines by qRT-PCR. LncRNA-HCG18 was silenced in AGS and MGC803 cells by the transfection of lncRNA-HCG18 siRNA (si-HCG18). MTT, transwell and Annexin V-PI double staining assay were performed to assess the proliferation, migration, invasion and apoptosis of GC cells. The expression of PI3K/Akt pathway-, apoptosis-, and migration-related proteins were detected by Western blot. An activator of PI3K/Akt pathway 740 Y-P was used to activate the PI3K/Akt pathway in AGS cells. A human tumor xenograft model was established in mice to evaluate the effects of si-HCG18 in vivo.
Results: LncRNA-HCG18 was overexpressed in GC tissues and cells. Up-regulation of lncRNA-HCG18 was positively correlated with the stage of tumor node metastasis and invasion depth. Silencing of lncRNA-HCG18 suppressed the proliferation, migration and invasion, and induced the apoptosis of GC cells. Silencing of lncRNA-HCG18 blocked the PI3K/Akt pathway. The intervention of 740Y-P reversed the anti-tumor effect of lncRNA-HCG18 on GC cells. In addition, silencing of lncRNA-HCG18 suppressed the growth of GC xenografts in mice.
Conclusion: Silencing of lncRNA-HCG18 inhibited the tumorigenesis of GC through blocking the PI3K/Akt pathway, suggesting a novel therapeutic target for GC.
Keywords: gastric cancer, lncRNA-HCG18, PI3K/Akt pathway, proliferation, migration