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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-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Dr William Cho
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