Regulation of miR-27a-3p/FBXW7 axis by increasing the level of lncRNA AC138128.1 to mitigate gastric cancer progression.

Abstract

Background: Gastric cancer (GC) has a poor prognosis due to its recurrence and metastasis. This research aims to investigate the potential regulatory mechanisms of AC138128.1 in GC.

Methods: A total of 124 GC patients were enrolled. RT-qPCR was used to assess AC138128.1, miR-27a-3p, and mRNA levels. Cell proliferation, migration, and invasion were assessed using CCK-8 and Transwell assays, respectively. Kaplan-Meier curves were used to validate patient survival. Targeted interactions among AC138128.1, miR-27a-3p, and FBXW7 were verified via DLR assays, with Pearson correlation analysis assessing relationships among the three groups. GO and KEGG were used to analyze the biological information of miR-27a-3p target genes.

Results: AC138128.1 is downregulated in GC tissues, miR-27a-3p level is upregulated. AC138128.1 negatively regulates miR-27a-3p. Patients with GC in the low AC138128.1 level group exhibited lower 5-year survival rates. Transfection with oe-AC138128.1 reduces miR-27a-3p levels, significantly inhibiting cell growth and invasiveness. However, when the miR-27a-3p level is increased, this inhibitory effect is reversed. Additionally, the downstream target genes of miR-27a-3p are primarily enriched in the PI3K-Akt signaling pathway. FBXW7 expression was downregulated in GC tissues. AC138128.1 expression positively correlated with FBXW7, whereas miR-27a-3p expression negatively correlated with FBXW7.

Conclusions: This study provides the first evidence that AC138128.1 is downregulated in GC cell lines and holds significant potential as a prognostic biomarker for GC. Low levels of AC138128.1 enhance miR-27a-3p expression, thereby influencing the invasiveness of GC cells and potentially promoting GC progression.