title: Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation.
abstract: There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT. Liver Transplantation 22 665-676 2016 AASLD.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Soejima
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yoshizumi
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Uchiyama
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ikegami
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Yo-Ichi
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Harimoto
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Itoh
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics*; D016031:Liver Transplantation; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D010534:Peritoneal Neoplasms / Q000556:secondary; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C522576:MIRN18A microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C531408:mirn199 microRNA, human; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3