Journal
ONCOLOGY REPORTS
Volume 41, Issue 3, Pages 1638-1648Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2018.6948
Keywords
liver cancer; miR-498; ZEB2; proliferation; migration
Categories
Funding
- National Natural Science Foundation of China [81672416, 81572075]
- Key Research and Development Project of Zhenjiang [SH2015034]
- Major Research and Development Project of Jiangsu Province [BE2015667]
- Project of Jiangsu Provincial Commission of Health and Family Planning [LGY2017024]
- Starting Foundation for Senior Talents of Jiangsu University [13JDG086]
- Qing Lan Project of Jiangsu Province
- Foundation for Young Academic Leader of Jiangsu University
- '333' project of Jiangsu Province
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MicroRNAs (miRNAs) play critical roles in the growth, metastasis and therapeutic resistance of liver cancer. Accumulating evidence suggests that miR-498 is aberrantly expressed in several human malignancies. However, the role and underlying mechanism of miR-498 in liver cancer remain unclear. In the present study, we investigated the potential roles and clinical value of miR-498 in liver cancer. We found that the miR-498 expression level was significantly lower in liver cancer patient tissues than that in healthy control tissues. The expression of miR-498 was also decreased in liver cancer cell lines compared to that noted in a normal human normal liver cell line. miR-498 overexpression markedly inhibited liver cancer cell proliferation, migration and invasion. miR-498 overexpression induced cell cycle arrest and apoptosis while it suppressed epithelial-mesenchymal transition (EMT) in liver cancer cells. Bioinformatic analysis and luciferase reporter assay further identified zinc finger E-box binding homeobox 2 (ZEB2) as a novel target of miR-498. Furthermore, ZEB2 knockdown recapitulated the inhibitory effects of miR-498 overexpression in liver cancer cells. ZEB2 overexpression rescued the inhibition of liver cancer cell proliferation, migration, and invasion by miR-498, indicating that ZEB2 acts as a downstream effector of miR-498 in liver cancer cells. Thus, we demonstrated that miR-498 suppresses the growth and metastasis of liver cancer cells, partly at least, by directly targeting ZEB2, suggesting that miR-498 may serve as a potential biomarker for the diagnosis and therapy of liver cancer.
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