N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis

Abstract

ABSTRACT Gastric cancer is one of the most common malignant tumors. Long non-coding RNAs play crucial roles in gastric cancer progression. This study investigated the effect of LINC01320 on malignant behaviors of gastric cancer cells and explored its possible molecular mechanism. LINC01320 expression in gastric cancer tissues and cell lines was measured by qRT-PCR. Cell proliferation, transwell, and cell cloning assays were used to detect the effect of LINC01320 on the proliferation, migration, and invasion abilities, respectively, of gastric cancer cells. Bioinformatics analysis was used to predict the binding of miR-495-5p with LINC01320 and RAB19. A luciferase reporter assay was performed to verify their interactions. Finally, the N6-methyladenosine (m6A) modification of LINC01320 by METTL14 was identified through RIP experiments. LINC01320 was highly expressed in gastric cancer tissues and cells. LINC01320 overexpression promoted the proliferation, migration, and invasion of gastric cancer cells, while LINC01320 knockdown exerted the opposite effects. Moreover, miR-495-5p was predicted and demonstrated to target LINC01320 and RAB19. LINC01320 sponged miR-495-5p to regulate the expression of RAB19. Additionally, LINC01320-induced increases in cell viability, migration, and invasion of gastric cancer were alleviated by miR-495-5p and silenced RAB19. Furthermore, epigenetic studies showed that METTL14-mediated m6A modification led to LINC01320 up-regulation. METTL14 regulated the m6A modification of LINC01320. Overexpressed LINC01320 contributed to the aggressive phenotype of gastric cancer cells via regulating the miR-495-5p/RAB19 axis. This finding may provide new potential targets for treating gastric cancer.