期刊
JOURNAL OF CANCER
卷 12, 期 20, 页码 6058-6070出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.61311
关键词
Dihydromyricetin; cholangiocarcinoma; miR-455-3p; epithelial-mesenchymal transition
类别
资金
- National Natural Science Foundation of China [81703818, 81400331, 81703767]
- Natural Science Foundation of Hunan Province [2018JJ3731, 2019JJ40430, 2019JJ50680, 2019JJ50891]
- Wu Jieping Medical Foundation [320.6750.2020-4-35, 320.6750.2020-4-36]
- Self-financing Scientific Research Project of Guangxi Health Commission [Z20201003]
DMY treatment inhibits cell proliferation and EMT in CCA cell lines by regulating miR-455-3p and its target ZEB1. Inhibition of miR-455-3p expression abolishes DMY's inhibitory effects on tumor growth and EMT in both CCA cells and cell-engrafted nude mice. DMY also suppresses the expressions of p-PI3K and p-AKT, suggesting its potential as a treatment option for CCA.
Cholangiocarcinoma (CCA) leads to poor prognosis due to high aggressiveness and common chemoresistance. Dihydromyricetin (DMY), the main bioactive compound isolated from Ampelopsis grossedentata, exhibits broad anti-tumor effects. This study aimed to investigate the inhibitory effect of DMY on CCA tumor growth and epithelial-mesenchymal transition (EMT) and its underlying mechanism in CCA. DMY treatment significantly inhibited cell proliferation and EMT in CCA cell lines. The expression of ZEB1 and vimentin were down-regulated, while the level of E-cadherin was increased after DMY treatment. By analyzing the TCGA dataset, we found that miR-455 expression was significantly downregulated, while the level of ZEB1 was up-regulated in human CCA tumor tissues compared to normal samples. Mechanistic studies showed that ZEB1 was a direct target of miR-455-3p in CCA. Moreover, DMY treatment potently increased miR-455-3p expression and inhibited ZEB1 expression. Inhibition of miR-455-3p expression abolished DMY's inhibitory effects on tumor growth and EMT in both CCA cells and cell-engrafted nude mice. Finally, DMY significantly suppressed the expressions of p-PI3K and p-AKT, while silencing miR-455-3p remarkably abrogated the inhibitory effect. In conclusion, DMY suppresses tumor growth and EMT through regulating miR-455-3p in human cholangiocarcinoma, suggesting a potential option for CCA treatment.
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