1. Let-7 inhibits self-renewal of hepatocellular cancer stem-like cells through regulating the epithelial-mesenchymal transition and the Wnt signaling pathway.
- Author
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Bin Jin, Wei Wang, Xiang-xin Meng, Gang Du, Jia Li, Shi-zhe Zhang, Bing-hai Zhou, and Zhi-hao Fu
- Subjects
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LIVER cancer , *CANCER cells , *CELLULAR control mechanisms , *EPITHELIAL cells , *MESENCHYMAL stem cells , *WNT signal transduction - Abstract
Background: Tumor suppressive let-7 miRNAs are universally down-regulated in human hepatocellular carcinoma (HCC) versus normal tissues; however, the roles and related molecular mechanisms of let-7 in HCC stem cells are poorly understood. Methods: We examined the inhibitory effect of let-7 miRNAs on the proliferation of MHCC97-H and HCCLM3 hepatic cancer cells by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, which was further confirmed by apoptosis and cell cycle studies. The sphere-forming assay was used to study the effects of let-7a on stem like cells. Through western blot, immunofluorescence and the luciferase-reporter assay, we explored the activity of epithelial-mesenchymal transition (EMT) signaling factors in HCC cells. qRT-PCR was applied to detect miRNA expression levels in clinical tissues. Results: Let-7a effectively repressed cell proliferation and viability, and in stem-like cells, also let-7a decreased the efficiency of sphere formation.in stem-like cells. The suppression of EMT signaling factors in HCC cells contributed to let-7's induced tumor viability repression and Wnt activation repression. Besides, Wnt1 is critical and essential for let-7a functions, and the rescue with recombinant Wnt1 agent abolished the suppressive roles of let-7a on hepatospheres. In clinical HCC and normal tissues, let-7a expression was inversely correlated with Wnt1 expression. Conclusions: Let-7 miRNAs, especially let-7a, will be a promising therapeutic strategy in the treatment of HCC through eliminating HCC stem cells, which could be achieved by their inhibitory effect on the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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