Comprehensive analysis and identification of the circ_0084615/miR-451a/MEF2D axis in benzo(a)pyrene exposed tumor cells in hepato-carcinogenesis

• Published in: Food and chemical toxicology 2023-06, Vol.176, p.113810-113810, Article 113810
• Main Authors: Mu, Wei, Gu, Pengfei, Song, Weiwei, Zhu, Tengfei, Wang, Wenbo, Zhou, Yanfeng
• Format: Article
• Language: English
• Subjects: Animals; Benzo(a)pyrene; Benzo(a)pyrene - toxicity; Carcinogenesis - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation; Circular RNA; Competing endogenous RNA; Gene Expression Regulation, Neoplastic; Hepatocellular carcinoma; Humans; In Situ Hybridization, Fluorescence; Liver Neoplasms - genetics; Liver Neoplasms - pathology; MEF2 Transcription Factors - genetics; MEF2 Transcription Factors - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Prognostic biomarker; RNA, Circular - genetics; RNA, Messenger
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.113810

Hepatocellular carcinoma (HCC) is caused by genetic and epigenetic alterations, as well as abnormal lifestyle and dietary habits, including contaminated food intake. Benzo(a)pyrene (B[a]P), derived from deep-fried meats, is regarded as the main dietary factor for tumorigenesis in epidemiological investigations. Although various studies have illustrated the adverse effects of B[a]P in malignancy through cell and animal models, the correlation between B[a]P exposure and clinical data remain to be explored. In the present study, we analyzed and identified novel B[a]P-associated circular RNA (circRNA) from microarray databases of liver tumor cells and HCC patient samples. Considering that circRNA regulates mRNA as a miRNA sponge, molecular circRNA-miRNA-mRNA interactions based on the stimulation of B[a]P exposure were predicted and established. Furthermore, up-regulated circ_0084615 in B[a]P-treated tumor cells was verified as a miRNA sponge via fluorescence in situ hybridization (FISH) assays, and the repression between circ_0084615 and target miR-451a exhibited a contrasting effect on hepatocarcinogenesis. Therefore, we performed integrated bioinformatics analysis and molecular experiments to establish the circ_0084615/miR-451a/MEF2D pathway, which provided a better understanding of the adverse effects of fried food preference on human health. •Integrated analysis of circRNA expression from GEO database to identify the tumorigenesis molecules.•The landscape of benzo(a)pyrene-induced bioactive circRNAs in the liver tumor cells.•Prediction of the ceRNA regulatory network in benzo(a)pyrene-exposed liver tumor cells.•The circ_0084615/miR-451a/MEF2D pathway promotes HCC progression in the heat-treated food preference population.