Back to Journals » OncoTargets and Therapy » Volume 11

microRNA-26a induces a mitochondrial apoptosis mediated by p53 through targeting to inhibit Mcl1 in human hepatocellular carcinoma

Authors Gao X, Zhu Y, Li JH, Wang X, Zhang X, Yi C, Yang X

Received 27 December 2017

Accepted for publication 1 March 2018

Published 19 April 2018 Volume 2018:11 Pages 2227—2239

DOI https://doi.org/10.2147/OTT.S160895

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr William Cho


Xiao-Mei Gao,* Ying Zhu,* Jian-Hua Li,* Xiang-Yu Wang, Xiao-Fei Zhang, Chen-He Yi, Xin Yang

Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China

*These authors contributed equally to this work

Aim: We have previously found that microRNA-26a (miR-26a) is a potential tumor suppressor in hepatocellular carcinoma (HCC). In this study, we further explored the roles of miR-26a in HCC apoptosis.
Methods: miR-26a expression levels were detected in HCC tissues by real-time PCR. Statistical analysis was performed to explore the correlation between miR-26a expression and apoptotic cells and the antiapoptotic protein levels. In vitro assays were performed to investigate the roles of miR-26a in HCC apoptosis. The immunohistochemical staining analysis, Western blot, and luciferase reporter assay were performed to evaluate the relationship between miR-26a and its potential upstream regulating and downstream target genes. The potential mechanism of the combination treatment of interferon-α1b (IFN-α1b) and 5-fluorouracil (5-FU) was explored by in vitro and in vivo assays.
Results: miR-26a levels were significantly associated with the number of apoptotic cells and inversely correlated with the protein levels of Bcl-2, Bcl-xL, and Mcl1 in HCC tissues. Furthermore, miR-26a was proved to induce the mitochondrial apoptosis in vitro by directly targeting to inhibit Mcl1 in HCC cells. Moreover, p53 was demonstrated to mediate miR-26a-induced apoptosis, by activating its promoter in HCC. Meanwhile, the combination treatment of IFN-α1b and 5-FU could induce the expression of p53, which then upregulated miR-26a and downregulated Mcl1 levels, and finally promoted the apoptosis of HCC cells through a mitochondrial pathway.
Conclusion: These findings highlight the important and related molecular mechanism of miR-26a in the regulation of apoptosis and implicate the potential application of combination of IFN-α1b and 5-FU in HCC treatment.

Keywords: miR-26a, p53, Mcl1, mitochondrial apoptosis, hepatocellular carcinoma
 

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]