Molecular mechanisms by which benzo[ghi]perylene promotes cell proliferation and DNA damage via downregulation of the chimeric RNA TVP23C-CDRT4/miR-24–3p axis

We investigated the toxicity of benzo[ghi]perylene (BghiP), a prevalent polycyclic aromatic hydrocarbon (PAH). Transcriptome analysis of control and BghiP-exposed human bronchial epithelial cells (BEAS-2B) led to the identification of a novel chimeric RNA (chRNA), TVP23C-CDRT4, whose expression is significantly downregulated by BghiP in vitro and in vivo. Funcionally, overexpression of TVP23C-CDRT4 inhibited BghiP-induced cell proliferation and DNA damage, whereas its knockdown exacerbated these detrimental effects. Mechanistically, TVP23C-CDRT4 acts as a molecular decoy for miR-24-3p. Thus, BghiP-induced suppression of TVP23C-CDRT4 unveils a novel mechanism of PAH toxicity, highlighting its anti-proliferative and genome-protective roles relevant to the early stages of carcinogenesis. • Identifies novel BghiP-induced chRNA TVP23C-CDRT4 downregulated. • TVP23C-CDRT4 overexpression inhibits cell proliferation and reduces DNA damage. • TVP23C-CDRT4 acts as a molecular sponge for miR-24-3p to exert protective effects. • BghiP toxicity involves suppressing protective chRNA TVP23C-CDRT4/miR-24-3p axis.