LncRNA ABCA9-AS1 as a ceRNA Promotes Gastric Cancer Progression by Sponging miR-497-5p to Regulate KIF23 Expression.
Abstract
INTRODUCTION Long noncoding RNAs (lncRNAs) have emerged as important modulators in the molecular pathology of cancer. lncRNA ABCA9-AS1 is a newly identified lncRNA, and its role in gastric cancer has not yet been reported.
Objective
To investigate the effects of lncRNA ABCA9-AS1 on the proliferation and metastasis of gastric cancer cells and to explore its role in the miR-497-5p/KIF23 signalling cascade.
Methods
A gastric cancer-specific ceRNA network (lncRNA-miRNA-mRNA) was constructed using RNA-seq and miRNA-seq data from TCGA. qRT-PCR was used to detect the expression levels of the target genes in gastric cancer cells (AGS, HGC-27, MKN28) and human gastric mucosal epithelial cells (GES-1). Knockdown of lncRNA ABCA9-AS1 was achieved using specific siRNA, while overexpression of KIF23 was achieved using a pcDNA3.1-based overexpression plasmid. The proliferative capacity of gastric cancer cells was assessed using CCK-8 and colony formation assays. Cell migration and invasion were evaluated by Transwell migration and Matrigel invasion assays, respectively.
Results
A gastric cancer-specific lncRNA-associated ceRNA network was constructed. qRT-PCR showed significant upregulation of lncRNA ABCA9-AS1 in gastric cancer cells (AGS, HGC-27, MKN28), with concomitant downregulation of miR-497-5p and upregulation of KIF23. In AGS cells, ABCA9-AS1 knockdown increased miR-497-5p expression and reduced KIF23 expression, while miR-497-5p mimics suppressed KIF23 expression. Functional assays confirmed that ABCA9-AS1 knockdown and miR-497-5p overexpression inhibited the proliferation, migration, and invasion of AGS cells. Conversely, KIF23 restoration or miR-497-5p inhibition reversed these effects, as did KIF23 co-expression with miR-497-5p mimics.
Discussion
Our results highlight lncRNA ABCA9-AS1 as a novel and promising prognostic biomarker that promotes gastric cancer progression by acting as a ceRNA to modulate the miR-497-5p/KIF23 axis.
Conclusion
lncRNA ABCA9-AS1 is aberrantly upregulated in gastric cancer. As a ceRNA, it sponges miR-497-5p to increase KIF23 expression and enhance the proliferation, migration, and invasion of gastric cancer cells.