Abstract:

Objective To explore the mechanism of aflatoxin B1（AFB1）-induced liver cancer in rats and the alternative splicing events that blocked the molecular mechanism of liver cancer. Methods Model of AFB1-induced liver cancer in rats was constructed， total RNA from rat liver tissue was extracted，and Illumina HiSeq 2000 sequencing platform was used to sequence RNA-seq  in rat liver tissue. Using rat genomic data as a reference，332 known reference genes with multiple  alternative splicing variants were currently included in the study. The rat genomic alternative splicing events were identified and analyzed， and biological process （BP）enrichment analysis for GO categorization of alternative spliced genes with differentially expressed was conducted. Results Compared with the control group，18 alternative splicing patterns of genes in the non-cancer group showed a big difference，and mainly enriched in the stimulatory response function. Compared with the control group，37 alternative splicing patterns of genes in the cancer group were different，and mainly enriched in the stimulation response and cell proliferation regulation function. Compared with the non-cancer group，the alternative splicing patterns of 32 genes in the cancer group were significantly different，mainly enriched in the cell proliferation regulation function. In the cancer group，7 splicing patterns of genes involved in cell proliferation regulation were found to be abnormal. The alternative splicing patterns of IgfI，Carm1，and Tcfe2a were significantly different between the cancer group，the non-cancer group，and the control group. Conclusion Alternative splicing changes of IgfI，Carm1，Tcfe2a may play an important role in AFB1-induced liver cancer formation in rats.

Key words: Liver neoplasms, RNA-seq, Aflatoxin, Alternative splicing, Animal model