Chemoresistance mediated by
insulin resistance (IR) in HCC has already been validated. However, the underlying mechanism, especially the involvement of
microRNAs (
miRNAs) was unelucidated. In this study,
miRNA microarrays and bioinformatics methods were employed to determine the dysregulation of
miRNA by IR in HCC cells, and quantitative RT-PCR (qRT-PCR) was applied to valid the
miRNA array data. Of all the 2006
miRNAs screened, 32
miRNAs were found up or down regulated between the HepG2/IR cells and its parental cells. Further literature mining revealed that some of these
miRNAs may function as oncogenes or
tumor suppressors that contribute to
tumor progression, recurrence, and
metastasis which eventually lead to chemotherapeutic resistance. Interestingly, bioinformatics analysis by Gene Ontology (GO) enrichment pathway indicating that function of the predicted target genes of these dysregulated
miRNAs were significantly enriched in the processes related with biosynthesis, catabolism, modification etc., and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping showed that the
biological regulatory mechanisms were integrated in
cancer-related pathways. Moreover, we also constructed a network which connected the differentially expressed
miRNAs to target genes, GO enrichments and KEGG pathways to reveal the hub
miRNAs, genes and pathways. Collectively, our present study demonstrated the possible
miRNAs and predicted target genes involving in the pathophysiology of
insulin resistant HCC, providing novel insights into the molecular mechanisms of multidrug resistance in the
insulin resistant HepG2 cells.