Growing evidence indicates that changes in
microRNA (
miRNA) expression in
cancer induced by chemical
carcinogens play an important role in
cancer development and progression by regulating related genes. However, the mechanisms underlying
miRNA involvement in hepatocarcinogenesis induced by
polycyclic aromatic hydrocarbons (PAHs) remain unclear. Thus, the identification of aberrant
miRNA expression during PAH-induced
cancer cell migration will lead to a better understanding of the substantial role of
miRNAs in
cancer progression. In the present study,
miRNA expression profiling showed significant upregulation of miR-181a, -181b, and -181d in human
hepatocellular carcinoma cells (HepG2 line) exposed to
benzo[a]anthracene (BA) and
benzo[k]fluoranthene (BF). MAPK phosphatase-5 (MKP-5), a validated miR-181 target that deactivates MAPKs, was markedly suppressed while phosphorylation of
p38 MAPK was increased after BA and BF exposure. The migration of HepG2 cells, observed using the scratch wound-healing assay, also increased in a dose-dependent manner. Depletion of miR-181 family members by
miRNA inhibitors enhanced the expression of MKP-5 and suppressed the phosphorylation of
p38 MAPK. Furthermore, the depletion of the miR-181 family inhibited
cancer cell migration. Based on these results, we conclude that the miR-181 family plays a critical role in PAH-induced hepatocarcinogenesis by targeting MKP-5, resulting in the regulation of
p38 MAPK activation.