title: Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma cells.
abstract: Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.
authors.affiliation: Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
authors.forename: Suning
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
authors.forename: Rongquan
authors.identifier: 0000-0002-7752-2080
authors.initials: R
authors.lastname: He
authors.affiliation: Research Department, Affiliated Cancer Hospital, Guangxi Medical University, 71 Hedi Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Rong
authors.affiliation: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
authors.forename: Gang
authors.identifier: 0000-0002-4864-1451
authors.initials: G
authors.lastname: Chen
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000068818:Cetuximab; D004357:Drug Synergism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D000068818:Cetuximab