Inhibition of c-FLIP expression by miR-512-3p contributes to Taxol-induced apoptosis in hepatocellular carcinoma cells

  • Authors:
    • Feng Chen
    • Hai-Hong Zhu
    • Lin-Fu Zhou
    • Shan-Shan Wu
    • Jing Wang
    • Zhi Chen
  • View Affiliations

  • Published online on: Saturday, May 1, 2010
  • Pages: 1457-1462 DOI: 10.3892/or_00000784

Abstract

Dysregulation of the antiapoptotic protein cellular FLICE-like inhibitory protein (c-FLIP) has been proven to be associated with tumorigenesis and progress of most human cancers. However, its aberrant expression is poorly elucidated. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in tumorigenesis through negatively regulating gene expression. Our study disclosed that c-FLIP was overexpressed in HepG2 hepatocellular carcinoma cells and down-regulation of c-FLIP enhanced Taxol-induced apoptosis. Taxol induction significantly decreased the protein level of c-FLIP. While no decrease in c-FLIP mRNA level was observed, indicating Taxol decreased c-FLIP expression through a post-transcriptional mechanism. miR-512-3p was a predicted suppressor of c-FLIP and exhibited an opposite expression manner to c-FLIP before and after Taxol induction. Luciferase report assay demonstrated miR-512-3p negatively regulated c-FLIP expression via a conserved miRNA-binding site in 3' untranslated region (3'UTR) of c-FLIP. The decrease of c-FLIP protein due to transfection of miR-512-3p further validated the inhibitory effect of miR-512-3p on c-FLIP. Additional transfection of miR-512-3p remarkably promoted Taxol-induced apoptosis, confirming its involvement in apoptosis. In summary, our study disclosed a novel regulatory mechanism that down-regulation of c-FLIP by miR-512-3p contributed to Taxol-induced apoptosis. Importantly, the pivotal role of miR-512-3p in determining c-FLIP abundance helps to broaden the implications for cancer therapy by developing small molecules to directly target c-FLIP at mRNA level.
Journal Cover

May 2010
Volume 23 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

2014 Impact Factor: 2.301
Ranked #31/211 Oncology
(total number of cites)

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APA
Chen, F., Zhu, H., Zhou, L., Wu, S., Wang, J., & Chen, Z. (2010). Inhibition of c-FLIP expression by miR-512-3p contributes to Taxol-induced apoptosis in hepatocellular carcinoma cells . Oncology Reports, 23, 1457-1462. http://dx.doi.org/10.3892/or_00000784
MLA
Chen, F., Zhu, H., Zhou, L., Wu, S., Wang, J., Chen, Z." Inhibition of c-FLIP expression by miR-512-3p contributes to Taxol-induced apoptosis in hepatocellular carcinoma cells ". Oncology Reports 23.5 (2010): 1457-1462.
Chicago
Chen, F., Zhu, H., Zhou, L., Wu, S., Wang, J., Chen, Z." Inhibition of c-FLIP expression by miR-512-3p contributes to Taxol-induced apoptosis in hepatocellular carcinoma cells ". Oncology Reports 23, no. 5 (2010): 1457-1462. http://dx.doi.org/10.3892/or_00000784