# LncRNA FLG-AS1 inhibits esophageal squamous cell carcinoma by regulating the miR-23a-3p/HOXD10 axis

## TL;DR

This study shows that the lncRNA FLG-AS1 helps fight esophageal cancer by controlling the miR-23a-3p/HOXD10 pathway, reducing cancer spread and drug resistance.

## Contribution

The study identifies a novel regulatory mechanism involving FLG-AS1, miR-23a-3p, and HOXD10 in ESCC progression and cisplatin resistance.

## Key findings

- FLG-AS1 and HOXD10 are underexpressed in ESCC, while miR-23a-3p is overexpressed.
- FLG-AS1 inhibits miR-23a-3p, which in turn suppresses HOXD10, promoting ESCC progression.
- Higher FLG-AS1 and HOXD10 levels correlate with better survival in ESCC patients.

## Abstract

Esophageal cancer (EC) is the ninth most common cancer worldwide that kills about 300,000 people each year. Esophageal squamous cell carcinoma (ESCC) is the main type of EC. Long non-coding RNAs (lncRNAs) have been proven to be severely dysregulated in EC, but the functions of more lncRNAs still need to be explored.

To explore the new molecular mechanism of ESCC development, the online biology databases (GEO, lncRNASNP2, Starbase, TargetScan) were employed to investigate the novel pathways implicated. To assess the expression levels of FLG-AS1, miR-23a-3p, and associated genes, we utilized RT-qPCR. The expression of HOXD10 was evaluated through western blotting analysis. To elucidate the regulatory interactions among FLG-AS1, miR-23a-3p, and HOXD10, a combination of dual luciferase assays, silencing techniques, and overexpression studies were conducted. The migratory and invasive capabilities of the cells were examined using a transwell apparatus. Cell viability was measured employing the CCK-8 assay, while apoptosis was detected through Annexin V/PI double staining methodology. Concentrations of glucose and lactic acid were determined utilizing appropriate biochemical kits.

FLG-AS1 and HOXD10 exhibited low expression levels in ESCC cells, whereas miR-23a-3p was found to be highly expressed. FLG-AS1 was observed to reduce the free level of miR-23a-3p by directly binding to it, and in turn, miR-23a-3p inhibited the expression of HOXD10 by targeting its mRNA. The overexpression of FLG-AS1 and HOXD10 resulted in the attenuation of anaerobic glycolysis, as well as a decrease in the migratory and invasive capabilities of ESCC cells, effectively reversing their resistance to cisplatin. Conversely, the upregulation of miR-23a-3p yielded opposing effects. Furthermore, ESCC patients exhibiting elevated levels of FLG-AS1 and HOXD10, alongside reduced expression of miR-23a-3p, demonstrated a significantly higher 5-year survival rate post-surgery.

FLG-AS1 effectively inhibits the progression of ESCC and counters cisplatin resistance through the modulation of the miR-23a-3p/HOXD10 axis. This is a new mechanism affecting ESCC and will provide new ideas for the targeted therapy of ESCC.

The online version contains supplementary material available at 10.1186/s41065-025-00461-0.