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Tumor Biology

, Volume 36, Issue 11, pp 8661–8670 | Cite as

Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway

  • Yanxia Sui
  • Xiaoqiang Zheng
  • Dongli Zhao
Research Article

Abstract

Rab31 belongs to the Ras superfamily of small GTP-binding proteins, which has been found to regulate the vesicle transport from the Golgi apparatus to early and late endosomes. The investigation here detected the expression of Rab31 in 96 patients with hepatocellular carcinoma (HCC) and tried to identify its significance on outcome of HCCs after liver resection. By immunohistochemistry staining, it was found that Rab31 expression in HCC tissues was remarkably higher than that in adjacent liver tissues. Aberrant Rab31 overexpression in HCC tissues was identified to be associated with worse prognosis after liver resection. Univariate analysis showed that advanced tumor–nodes–metastasis (TNM) staging of HCC, intrahepatic metastases, portal vein invasion, and higher Rab31 were the predictive factors of poor prognosis. Multivariate analysis demonstrated that intrahepatic metastases and higher Rab31 were the independent prognostic factors. Furthermore, forced expression of Rab31 in Huh7 cells was found to promote cell growth via upregulation of Bcl-2/BAX ratio induced by PI3K/AKT. Correspondingly, silencing Rab31 induced cell apoptosis and in turn suppressed the growth capacity of MHCC97 cells in vitro. Taken together, this study provides the evidence of Rab31 overexpression in HCC, and Rab31 is potentially used as a novel biomarker of poor prognosis in patients with HCC. PI3K/AKT/Bcl-2/BAX axis was involved in Rab31-promoting HCC progression.

Keywords

Rab31 HCC Cell apoptosis PI3K/AKT signaling 

Notes

Acknowledgments

We thank all the patients who were willing to be recruited in this investigation. This investigation was supported by grants from Key Science and Technology Program of Shaanxi Province (No. 2013k12-03-14 to Dongli Zhao) and Science and Technology Plan Projects of Xian (SF1203(2) to Dongli Zhao).

Author contributions

Y.X.S, X. Zheng, and D.L.Z. carried out the molecular genetic studies and drafted the manuscript.

Conflicts of interest

None

Supplementary material

13277_2015_3626_Fig6_ESM.gif (106 kb)
Supplementary Figure 1

The DAPI staining in both Huh7 vector cells and Huh7 Rab31 cells. It seemed clearly that there were higher apoptotic percentage in Huh7 Vector cells (a) relative to Huh7 Rab31 cells (b). (GIF 105 kb)

13277_2015_3626_MOESM1_ESM.tif (861 kb)
High resolution image (TIFF 861 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of PathologyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  2. 2.Department of Oncology RadiotherapyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

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