The effect of low molecular weight-polycyclic aromatic hydrocarbons responsive hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 circuit on inflammatory response of A549 cells via the PI3K/AKT pathway and epithelial-mesenchymal transition process.

Abstract

Inflammation is widely recognized as an essential inducer of epithelial-mesenchymal transition (EMT). Meanwhile, competitive endogenous RNA (ceRNA) has been involved in a variety of disease processes. Therefore, the aim of the current study is to explore the regulation of ceRNA in the PI3K/AKT pathway and EMT mechanism in inflammatory response caused by low molecular weight-polycyclic aromatic hydrocarbons (LMW-PAHs). The A549 cells were treated with an equal mixture of phenanthrene (Phe) and fluorene (Flu), and total RNA was extracted for transcriptome sequencing. The target regulation of ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 was further determined for mechanism study. The mixture of Phe and Flu significantly upregulated the expressions of hsa_circ_0039929 and FGF2, down-regulated hsa-miR-15b-3p_R-1, activated the PI3K/AKT pathway and promoted EMT. Mechanically, the overexpression of hsa-miR-15b-3p_R-1 inhibited the expressions of hsa_circ_0039929 and FGF2, reversed the activation of PI3K/AKT signaling pathway by LMW-PAHs, and blocked the occurrence of EMT progression. Furthermore, knockdown of hsa_circ_0039929 could promote the levels of hsa-miR-15b-3p_R-1, while inhibit the expression of FGF2. The effects of hsa_circ_0039929 knockdowns on PI3K/AKT pathways and EMT progress resembled the hsa-miR-15b-3p_R-1 overexpression. All above suggested that ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 played an important role in the inflammation and EMT caused by LMW-PAHs.