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Prognostic Marker MicroRNA-125b Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells Via Suppressing Tumorigenic Molecule eIF5A2

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Abstract

Background

MicroRNAs (miRNAs) belong to a group of small non-coding RNA with differential expression in tumors, including hepatocellular carcinoma (HCC).

Aim

This study investigates the involvement of miR-125b in HCC.

Methods

Clinical analysis of miR-125b was performed using data derived from miRNA profiling and qPCR. Phenotypic changes of liver cell lines were examined after ectopic miR-125b expression. Lastly, bioinformatics analysis coupled with luciferase reporter assay was used to reveal the cellular target of miR-125b.

Results

A down-regulation of miR-125b was found in HCC tumors and cultured cells. Patients having tumors with ≥twofold reduction in miR-125b compared to adjacent non-tumor tissues contributed to 23 out of 49 HCC cases (46.9 %), while this down-regulation was usually found in patients with tumor venous infiltration and recurrence. miR-125b expression was also negatively correlated with increased serum AFP level and poor overall survival of patients. Ectopic expression of miR-125b led to alleviated tumor phenotypes of HCC cells. Among the 110 bioinformatically predicated candidates, 31 of them negatively correlated with miR-125b in HCC tumors for which one of them named eukaryotic translation initiation factor 5A2 (eIF5A2), known also as a liver oncofetal molecule, was validated to be a direct target of miR-125b in HCC.

Conclusions

This study has evidenced for the negative correlation of tumor miR-125b expression with poor prognosis of HCC patients. Expression of miR-125b can reverse the tumorigenic properties of cultured HCC cells via suppressing the tumorigenic molecule eIF5A2, thus postulating restoration of miR-125b level as a way to counteract liver tumorigenesis.

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Authors and Affiliations

  1. Department of Surgery, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong

    Felice H. Tsang, Victor Au, Wen-Jing Lu, Felix H. Shek, Angela M. Liu, John M. Luk, Sheung-Tat Fan, Ronnie T. P. Poon & Nikki P. Lee

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  1. Felice H. Tsang
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  2. Victor Au
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  4. Felix H. Shek
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Correspondence to Nikki P. Lee.

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Tsang, F.H., Au, V., Lu, WJ. et al. Prognostic Marker MicroRNA-125b Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells Via Suppressing Tumorigenic Molecule eIF5A2. Dig Dis Sci 59, 2477–2487 (2014). https://doi.org/10.1007/s10620-014-3184-5

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  • DOI: https://doi.org/10.1007/s10620-014-3184-5

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