Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation

Kazutoyo Morita, Ken Shirabe, Akinobu Taketomi, Yuji Soejima, Tomoharu Yoshizumi, Hideaki Uchiyama, Toru Ikegami, Yo Ichi Yamashita, Keishi Sugimachi, Norifumi Harimoto, Shinji Itoh, Tetsuo Ikeda, Yoshihiko Maehara

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18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)665-676
Number of pages12
JournalLiver Transplantation
Volume22
Issue number5
DOIs
Publication statusPublished - May 1 2016

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hepatology
  • Transplantation

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    Morita, K., Shirabe, K., Taketomi, A., Soejima, Y., Yoshizumi, T., Uchiyama, H., Ikegami, T., Yamashita, Y. I., Sugimachi, K., Harimoto, N., Itoh, S., Ikeda, T., & Maehara, Y. (2016). Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation. Liver Transplantation, 22(5), 665-676. https://doi.org/10.1002/lt.24400