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miR-301a Is a Candidate Oncogene that Targets the Homeobox Gene Gax in Human Hepatocellular Carcinoma

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Abstract

Background

MicroRNAs (miRNA) are a group of noncoding small RNAs that repress mRNA expression or induce mRNA degradation by binding to the 3′-untranslated regions of mRNAs. MiRNAs have been connected closely with the development of cancers such as hepatocellular carcinoma (HCC). However, the overexpression of microRNA-301a (miR-301a) has seldom been connected with tumorigenesis in HCC.

Aims

This study aims to characterize the function of upregulated miR-301a in HCC and show how the downstream growth arrest-specific homeobox (Gax) is negatively regulated by miR-301a.

Methods

The expression of miR-301a and Gax was detected using real-time PCR on HCC tissues and adjacent non-tumorous tissues. The luciferase reporter assay was used to assess Gax as a target of miR-301a. The nuclear factor κB (NF-κB) was measured by western blot after inhibiting miR-301a and enhancing Gax. The functions of miR-301a in vivo in HCC cells were measured by migration and invasion assays and flow cytometry.

Results

MiR-301a was significantly upregulated and Gax was downregulated in HCC samples compared with in the matching nontumoral tissues. Inhibiting miR-301a expression caused the upregulation of Gax and repressed NF-κB expression. We have shown that miR-301a plays an important role in increasing proliferation, migration and invasion and in inhibiting apoptosis of HCC cells.

Conclusions

miR-301a is frequently upregulated in HCC and modulates NF-κB expression by negatively regulating Gax.

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Authors and Affiliations

  1. Department of General Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China

    Peng Zhou, Wei Jiang, Lielin Wu, Ruimin Chang, Kemin Wu & Zhiming Wang

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  1. Peng Zhou
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  2. Wei Jiang
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  3. Lielin Wu
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  4. Ruimin Chang
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  5. Kemin Wu
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  6. Zhiming Wang
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Correspondence to Zhiming Wang.

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Zhou, P., Jiang, W., Wu, L. et al. miR-301a Is a Candidate Oncogene that Targets the Homeobox Gene Gax in Human Hepatocellular Carcinoma. Dig Dis Sci 57, 1171–1180 (2012). https://doi.org/10.1007/s10620-012-2099-2

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  • DOI: https://doi.org/10.1007/s10620-012-2099-2

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