title: miR‑222 regulates sorafenib resistance and enhance tumorigenicity in hepatocellular carcinoma.
abstract: The miR‑222 cluster has been demonstrated to function as oncomiR in human hepatocellular carcinoma (HCC). miR‑222 confers chemotherapy drug resistance in various cancers, including HCC. However, the effects and mechanisms by which miR‑222 regulates liver tumorigenicity and confers sorafenib (SOR) resistance remain unclear. Here we first investigated the miR‑222 effect on proliferation, cell cycle, apoptosis, migration and invasion of HCC. Our results demonstrated that miRNA inhibitors specially targeting miR‑222 significantly suppressed cellular proliferation, migration, invasion and G1/S transition of the cell cycle, and induced cell apoptosis in HepG2 cells. In addition, we investigated whether miR‑222 confers SOR resistance in HepG2 cells to explore it roles in acquisition of drug resistance. The results showed that miR‑222 inhibitors induced sensitivity to the antitumor effect of sorafenib in human HepG2 cells. Importantly, our study also showed that miR‑222 could regulate the expression of phosphorylation PI3K and AKT, which might contribute to miR‑222 conferred SOR resistance in HepG2 cells. In conclusion, this study demonstrates that miR‑222 can promote cell proliferation, migration and invasion, and decrease cell apoptosis, as well as enhance the resistance of HCC cells to sorafenib miR‑222 through activating the PI3K/AKT signaling pathway.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin Province, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin Province, P.R. China.
authors.forename: Songyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin Province, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin Province, P.R. China.
authors.forename: Bai
authors.initials: B
authors.lastname: Ji
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin Province, P.R. China.
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin Province, P.R. China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D009536:Niacinamide; D010671:Phenylurea Compounds; D000077157:Sorafenib; C525710:MIR222, human