Tumor Biology

, Volume 37, Issue 6, pp 7713–7718 | Cite as

Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion

Original Article

Abstract

Rab25 was reported to be associated with several human cancers and malignant biological behavior of cancer cells. The goal of the present study was to determine its expression pattern and biological function in human hepatocellular carcinoma (HCC). We examined Rab25 protein in 92 cases of HCC tissues and 3 HCC cell lines. The results showed that Rab25 was upregulated in HCC tissues and cells compared with normal liver tissues and cell line. Rab25 overexpression correlated with advanced tumor stage and nodal metastasis. Rab25 small interfering RNA (siRNA) was employed in Bel7402 and SK-Hep-1 cell lines. Cell Counting Kit-8 (CCK-8) assay and colony formation assay showed that Rab25 depletion blocked cell growth rate and inhibited colony formation ability. Transwell assay showed that Rab25 depletion negatively regulated the invading ability of HCC cells. To explore the possible mechanisms, we checked several signaling pathways and found that Rab25 depletion downregulated AKT phosphorylation. In addition, luciferase reporter assay showed that Rab25 depletion inhibited the Wnt signaling pathway and its target genes such as cyclin D1, c-myc, and MMP7. In conclusion, Rab25 is overexpressed in human HCC and contributes to cancer cell proliferation and invasion possibly through regulation of the Wnt signaling pathway.

Keywords

Hepatocellular carcinoma Rab25 Wnt 

Supplementary material

13277_2015_4606_Fig5_ESM.gif (9 kb)
Supplementary Figure 1

Expression of cyclin D1, c-myc, p-AKT and MMP7 in hepatocellular carcinoma cell lines and LO2 cell line. Western blot analysis showed that cyclin D1, c-myc, p-AKT and MMP7 expression was higher in Bel7402 and SK-Hep-1 cell lines than LO2 cell line. (GIF 9 kb)

13277_2015_4606_MOESM1_ESM.tif (86 kb)
High resolution image (TIF 86 kb)
13277_2015_4606_Fig6_ESM.gif (73 kb)
Supplementary Figure 2

AKT activator IGF-1 rescues HCC cells from growth and migration inhibition caused by Rab25 knockdown. A. Matrigel invasion assay showed that IGF-1 upregulated cell invasion in Rab25 siRNA treated HCC cells. B. CCK-8 assay showed that IGF-1 upregulated cell growth rate in Rab25 depleted Bel7402 and SK-Hep-1 cells. (GIF 72 kb)

13277_2015_4606_MOESM2_ESM.tif (953 kb)
High resolution image (TIF 952 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Donghua Geng
    • 1
  • Wenyan Zhao
    • 1
  • Yong Feng
    • 1
  • Jingang Liu
    • 2
  1. 1.Department of SurgeryThe Affiliated Shengjing Hospital of China Medical UniversityShenyangChina
  2. 2.Department of SurgeryThe Fourth Affiliated Hospital of China Medical UniversityShenyangChina

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