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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Journal of Experimental & Clinical Cancer Research 1/2018

Integrin-β5, a miR-185-targeted gene, promotes hepatocellular carcinoma tumorigenesis by regulating β-catenin stability

Zeitschrift:
Journal of Experimental & Clinical Cancer Research > Ausgabe 1/2018
Autoren:
Zhikun Lin, Ruiping He, Haifeng Luo, Chang Lu, Zhen Ning, Yuanhang Wu, Chuanchun Han, Guang Tan, Zhongyu Wang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13046-018-0691-9) contains supplementary material, which is available to authorized users.

Abstract

Background

The tumour microenvironment is essential for cancer progress and metastasis. Integrin-β5 (ITGB5), a member of the integrin family, has been implicated to mediate the interactions of cells with the extracellular matrix (ECM) and promote tumorigenesis in several malignancies. However, the role of ITGB5 in hepatocellular carcinoma (HCC) is still unknown.

Methods

The biological function of ITGB5 in HCC was investigated using migration, colony formation assays. The potential molecular mechanism of ITGB5 in regulating HCC tumorigenesis and β-catenin stabilization was investigated by western blotting, co-immunoprecipitation and ubiquitination assays. The expression level of ITGB5 mediated by miR-185 was confirmed by bioinformatic analysis, luciferase assay. The clinical significance of ITGB5 was based on human tissue microarray (TMA) analysis.

Results

Here, we found that the expression of ITGB5 is increased in HCC tissues. Elevated ITGB5 markedly facilitates HCC cell migration and tumorigenesis in vitro and in vivo. Further mechanistic studies revealed that ITGB5, as a partner of β-catenin, directly interacts with β-catenin and inhibits its degradation, thus leading to WNT/β-catenin activity. Subsequently, we also found that ITGB5 is a direct targeted gene of miR-185. The downregulation of miR-185 in HCC cells promotes an increase in ITGB5. An additional increase of ITGB5 is associated with β-catenin upregulation and a miR-185 decrease in HCC tissues.

Conclusions

Our data reveal that the miR-185-ITGB5-β-catenin pathway plays an important role in HCC tumorigenesis, and ITGB5 may be a promising specific target for HCC therapy.
Zusatzmaterial
Additional file 1: Figure S1. MHCC-97 L cell lysates were incubated with IgG (control) or ITGB5 antibody. The bounded proteins were eluted, resolved by SDS-PAGE, and visualized by CBB staining (upper panel). The band in the ITGB5 lane was identified as β-catenin by mass spectrometry. The obtained peptide sequences by mass spectrometry analysis were shown on the right.(B-D)The RNA levels of miR-185 were analysed by q-RT-PCR. (TIFF 552 kb)
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Literatur
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