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.

Effect of polycyclic aromatic hydrocarbons on cancer risk causally mediated via vitamin D levels

“…4 Due to the special chemical structure of PAHs, 5 multiple-product PAHs and their corresponding metabolites cause serious damage to the human body, [6][7][8][9] including (but not limited to) carcinogenicity and teratogenicity, reproductive and endocrine-disrupting effects, phototoxicity, genotoxicity, neurotoxicity, and immunotoxicity. [10][11][12][13][14] Typically, exposure to higher concentrations of PAH significantly increases cancer risk. 15,16 Moreover, nutrition epidemiology studies have shown an inverse association between PAH exposure and low intake of fruits and vegetables, which might be attributed to vitamin D deficiency.…”

“…Due to the special chemical structure of PAHs, 5 multiple‐product PAHs and their corresponding metabolites cause serious damage to the human body, 6–9 including (but not limited to) carcinogenicity and teratogenicity, reproductive and endocrine‐disrupting effects, phototoxicity, genotoxicity, neurotoxicity, and immunotoxicity 10–14 . Typically, exposure to higher concentrations of PAH significantly increases cancer risk 15,16 .…”