Song, Mi-Kyung Park, Yong-Keun Ryu, Jae-Chun 2024-01-20T11:03:09Z 2024-01-20T11:03:09Z 2021-09-04 2013-11-15 0041-008X https://pubs.kist.re.kr/handle/201004/127438 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. (C) 2013 Published by Elsevier Inc. English ACADEMIC PRESS INC ELSEVIER SCIENCE LYMPH-NODE METASTASIS HEPATOCELLULAR-CARCINOMA EXPRESSION KINASE INVASION GROWTH GENE RNA OVEREXPRESSION IDENTIFICATION Polycyclic aromatic hydrocarbon (PAH)-mediated upregulation of hepatic microRNA-181 family promotes cancer cell migration by targeting MAPK phosphatase-5, regulating the activation of p38 MAPK Article 10.1016/j.taap.2013.08.016 1 TOXICOLOGY AND APPLIED PHARMACOLOGY, v.273, no.1, pp.130 - 139 TOXICOLOGY AND APPLIED PHARMACOLOGY 273 1 130 139 scie scopus 000327290000015 2-s2.0-84884725701 Pharmacology & Pharmacy Toxicology Pharmacology & Pharmacy Toxicology Article LYMPH-NODE METASTASIS HEPATOCELLULAR-CARCINOMA EXPRESSION KINASE INVASION GROWTH GENE RNA OVEREXPRESSION IDENTIFICATION Polycyclic aromatic hydrocarbons (PAHs) Hepatocellular carcinoma (HCC) MicroRNA (miRNA) Migration MAPK phosphatase (MKP) p38 MAPK