# The Role of the LINC01376/miR-15b-3p_R-1/FGF2 Axis in A549 and H1299 Cells EMT Induced by LMW-PAHs

## TL;DR

This study shows how a specific RNA pathway contributes to cell changes caused by environmental pollutants, potentially offering new treatment targets.

## Contribution

The novel contribution is identifying the LINC01376/miR-15b-3p_R-1/FGF2 axis as a key driver of EMT in response to LMW-PAH exposure.

## Key findings

- LINC01376 overexpression promotes EMT, migration, and invasion in A549 and H1299 cells.
- LINC01376 acts as a ceRNA by binding miR-15b-3p_R-1, increasing FGF2 expression.
- The LINC01376/miR-15b-3p_R-1/FGF2 axis is a key mechanism in LMW-PAH-induced EMT.

## Abstract

Low-molecular-weight polycyclic aromatic hydrocarbons (LMW-PAHs), such as the 400 μM mixture of phenanthrene and fluorene used in this study, are prevalent environmental pollutants. Induction of epithelial–mesenchymal transition (EMT) by LMW-PAHs promote cell invasion and migration and contribute to disease pathogenesis. Long non-coding RNAs (lncRNAs) regulate gene expression by acting as competing endogenous RNAs (ceRNAs) that sequester microRNAs (miRNAs), a mechanism important for modulating EMT. Previously, regulation of the PI3K/AKT pathway and EMT in A549 cells are shown to occur through the hsa_circ_0039929/miR-15b-3p_R-1/FGF2 axis. Here, the functional role of the related LINC01376/miR-15b-3p_R-1/FGF2 axis in LMW-PAH-induced EMT was examined in A549 and H1299 cells. The miR-15b-3p_R-1 was downregulated, whereas LINC01376 and FGF2 were upregulated following LMW-PAH exposure. LINC01376 overexpression enhanced EMT, migration, and invasion. Interactions between miR-15b-3p_R-1 and FGF2, as well as direct binding of LINC01376 to miR-15b-3p_R-1, were confirmed experimentally. The results indicate that, in LMW-PAH-treated cells, LINC01376 functions as a ceRNA to sponge miR-15b-3p_R-1, thereby elevating FGF2 expression and promoting EMT, migration, and invasion. Identification of the LINC01376/miR-15b-3p_R-1/FGF2 regulatory axis highlighted as a key mechanism in LMW-PAH-driven EMT and suggests its potential as a therapeutic target in PAH-related pathologies.