MiR-429 increases the metastatic capability of HCC via regulating classic Wnt pathway rather than epithelial–mesenchymal transition
| Autor: | Shanhua Tang, Lei Chen, Guojun Hou, Jing Fu, Sheng-xian Yuan, Xin Chen, Meng-Chao Wu, Shao Li, Xi-Meng Lin, Chengjun Sui, Jing Tang, Dan Cao, Yang Yingcheng, Liang Li, Wentao Huang, Wen Wen, Hongyang Wang |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Carcinoma Hepatocellular Epithelial-Mesenchymal Transition MMP2 Molecular Sequence Data Real-Time Polymerase Chain Reaction Metastasis medicine Humans PTEN Epithelial–mesenchymal transition Neoplasm Metastasis Protein kinase B PI3K/AKT/mTOR pathway Base Sequence biology Liver Neoplasms PTEN Phosphohydrolase Wnt signaling pathway medicine.disease Wnt Proteins MicroRNAs Oncology Cancer research biology.protein Ectopic expression Signal Transduction |
| Zdroj: | Cancer Letters. 364:33-43 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2015.04.023 |
| Popis: | Epigenetic modification of miR-429 can manipulate liver T-ICs via targeting the RBBP4/E2F1/Oct4 axis, which might be crucial for hepatocarcinogenesis. However, whether miR-429 plays a role in regulating metastasis of hepatocellular carcinoma is still unclear. Using quantitative methylation analysis and real-time PCR, we have identified the hypomethylated status and upregulation of miR-429 in portal vein metastasis samples in comparison with their matched primary tumor. The ectopic expression of miR-429 dramatically induced the expression of MMP2/7/9 and enhanced HCC migration and invasion in vitro and in vivo in an EMT-independent manner. Both bioinformatics and functional studies elucidated the direct regulation of miR-429 on the 3'UTR of the PTEN gene, which leads to the activation of PI3K/AKT signaling and the nuclear translocation of β-catenin, eventually. Conversely, the knockdown of miR-429 efficiently recovered the expression of PTEN and attenuated PI3K/AKT/β-catenin-mediated cell metastasis. Clinically, the higher expression of miR-429 and nucleus relocation of β-catenin were identified as the adverse prognosis factors for recurrence-free survival (RFS) and overall survival (OS). In summary, our results here defined miR-429 as a key inducer for HCC pathogenesis and metastasis with potential utility for tumor intervention. |
| Databáze: | OpenAIRE |
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