LncRNA SLC2A1-AS1 facilitates tumor progression by targeting miR-508-5p/ FOXO1 axis in ovarian cancer cells

Epithelial ovarian cancer (EOC) has high tumor drug resistance, recurrence rate, and risk of metastasis.

To elucidate the role of the long non-coding RNA SLC2A1-AS1 in EOC.

A cohort of 140 EOC patients was enrolled. SLC2A1-AS1 and related transcripts were quantified by RT-qPCR. A panel of OC cell lines was then employed, and the oncogenic functions of SLC2A1-AS1 were systematically interrogated through CCK-8 proliferation, Transwell migration/invasion, and western blot analysis. Dual-luciferase reporter and RIP assays were performed to confirm the targeting interactions.

SLC2A1-AS1 expression was significantly increased in EOC tissues. High expression of SLC2A1-AS1 significantly increased the recurrence rate and mortality. Multifactor Cox suggested that high expression of SLC2A1-AS1 was an independent risk factor for overall survival (OS) and recurrence-free survival (RFS). In addition, SLC2A1-AS1 targeted miR-508-5p, which was generally down-regulated in EOC and was significantly negatively correlated with SLC2A1-AS1. Furthermore, miR-508-5p directly targeted FOXO1, a gene markedly up-regulated in EOC and inversely correlated with miR-508-5p levels. Depletion of SLC2A1-AS1 liberated miR-508-5p, which in turn binds FOXO1 mRNA, thereby suppressing proliferation, migration, and invasion of SKOV3 and OVCAR3 cells. This tumor-suppressive program could be largely weakened by miR-508-5p-inhibitor, underscoring the SLC2A1-AS1/miR-508-5p/FOXO1 axis as a critical driver of EOC aggressiveness. Consistent results were obtained in additional EOC cell lines A2780 and CAOV3, confirming the generalizability of the SLC2A1-AS1/miR-508-5p/FOXO1 axis across different cellular backgrounds.

SLC2A1-AS1 may drive the progression and recurrence of EOC through the miR-508-5p/FOXO1 axis.