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 language | English |
|---|---|
| Pages (from-to) | 665-676 |
| Number of pages | 12 |
| Journal | Liver Transplantation |
| Volume | 22 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2016 |
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All Science Journal Classification (ASJC) codes
- Surgery
- Hepatology
- Transplantation
Cite this
Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation. / Morita, Kazutoyo; Shirabe, Ken; Taketomi, Akinobu; Soejima, Yuji; Yoshizumi, Tomoharu; Uchiyama, Hideaki; Ikegami, Toru; Yamashita, Yo Ichi; Sugimachi, Keishi; Harimoto, Norifumi; Itoh, Shinji; Ikeda, Tetsuo; Maehara, Yoshihiko.
In: Liver Transplantation, Vol. 22, No. 5, 01.05.2016, p. 665-676.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Relevance of microRNA-18a and microRNA-199a-5p to hepatocellular carcinoma recurrence after living donor liver transplantation
AU - Morita, Kazutoyo
AU - Shirabe, Ken
AU - Taketomi, Akinobu
AU - Soejima, Yuji
AU - Yoshizumi, Tomoharu
AU - Uchiyama, Hideaki
AU - Ikegami, Toru
AU - Yamashita, Yo Ichi
AU - Sugimachi, Keishi
AU - Harimoto, Norifumi
AU - Itoh, Shinji
AU - Ikeda, Tetsuo
AU - Maehara, Yoshihiko
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84964780492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964780492&partnerID=8YFLogxK
U2 - 10.1002/lt.24400
DO - 10.1002/lt.24400
M3 - Article
C2 - 26783726
AN - SCOPUS:84964780492
VL - 22
SP - 665
EP - 676
JO - Liver Transplantation
JF - Liver Transplantation
SN - 1527-6465
IS - 5
ER -