期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 51, 期 1, 页码 470-486出版社
KARGER
DOI: 10.1159/000495242
关键词
Hepatocellular carcinoma; MicroRNA; EMT; Metastasis; Wnt; b-catenin
资金
- Natural Science Foundation of China [81472259]
- Natural Science Foundation of Guangdong Province [2014A030313042]
- Guangzhou Science and Technology Plan Projects [201510010292]
- Science and technology project of Guangdong Province [2015A020212007]
- Sun Yat-Sen University Clinical Research 5010 Program [2015004]
Background/Aims: MicroRNA-197 (miR-197) has been shown to play roles in epithelialmesenchymal transition (EMT) and metastasis. The Wnt/-catenin pathway is associated with EMT, but whether miR-197 regulatesWnt/-catenin remains unclear. This study was to demonstrate the role of miR-197 on the Wnt/-catenin pathway in hepatocellular carcinoma (HCC). Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-197 in 105 HCC specimens and 15 HCC cell lines. We tested the predicted target gene of miR-197 using a genetic report system. The role of miR-197 in HCC cell invasion and migration (wound healingand cell invasion and migrationby Transwell assays) and in an HCC xenograft modelwas analyzed. Results: Using a miRNA microarray analysis of HCC specimens and compared with non-metastatic HCC, miR-197 was identified as one of the most upregulated miRNAs in metastatic HCC. miR-197 expression was positively associated with the invasiveness of HCC cell lines. Metastatic HCC cells with high miR-197 expression had Wnt/-catenin signaling activation. High levels of miR-197 expression also promoted EMT and invasionHCC cells in vitro and in vivo. miR-197 directly targeted Axin-2, Naked cuticle 1 (NKD1), and Dickkopf-related protein 2 (DKK2), leading to inhibition of Wnt/-catenin signaling. High miR-197 expression was found in HCC specimens from patients with portal vein metastasis;high miR-197 expression correlated to the expression of Axin2, NKD1, and DKK2. Conclusion: miR-197 promotes HCC invasion and metastasis by activating Wnt/-catenin signaling. miR-197 could possibly be used as a prognostic marker and therapeutic target for HCC.
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