Rab23 is a potential biological target for treating hepatocellular carcinoma - PubMed (original) (raw)

Rab23 is a potential biological target for treating hepatocellular carcinoma

Yun-Jian Liu et al. World J Gastroenterol. 2007.

Abstract

Aim: To elucidate the role of Rab23 in hepatocellular carcinoma (HCC) by assessing the expression of Rab23 in HCC tissue and in HCC cell lines.

Methods: Primary tumors (n = 100) were stained with Rab23 antibodies using immunohistochemistry and in situ hybridization in tissue microarrays. Relationships between gene expression and pathology parameters were analysed. The biological significance of Rab23 in Hep-3B cells was examined by knocking down Rab23 gene expression. We designed a pair of double-stranded RNAs against human rab23 and transfected siRNA into Hep-3B cells. Rab23 expression in these cells was examined using RT-PCR and Western blots. We investigated cell growth by MTT assays and fluorescence-activated cell sorting.

Results: High cytoplasmic and nuclear expression of Rab23 was found in 38 of 71 (53.5%) and in 49 of 68 HCC patients (72%) respectively, which correlated with tumor size. HCC cell lines expressed Rab23. In Hep3B cells, siRNA for Rab23 decreased Rab23 mRNA by 4.5-fold and protein expression by 2-fold. Survival rates at 24 and 48 h for Hep-3B cells transfected with siRNA were lower and about 30% Hep-3B cells were apoptotic. Knocking down rab23 suppressed Hep3B cell growth, suggesting that rab23 could play an important role in Hep3B cell growth.

Conclusion: Rab23 is overexpressed and/or activated in HCC. Rab23 may be both a HCC predictor and a target for treating HCC.

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Figures

Figure 1

Figure 1

In situ hybridization using tissue microarrays.

Figure 2

Figure 2

Rab23 gene silencing in Hep-3B cells. Green fluorescence could be detected in siRNA-transfected Hep-3B cells (negative control group).

Figure 3

Figure 3

Expression of Rab23 in normal liver tissues and HCCs as seen by immunohistochemistry (A-C) and in situ hybridization (D-F).

Figure 4

Figure 4

Electrophoresis of the RT-PCR products of Rab23 mRNA in Hep-3B cells after being silenced by siRNA. Lane 1: marker 1500; Lane 2: blank control group; Lane 3: transfection group; Lane 4: negative control group.

Figure 5

Figure 5

Electrophoresis of the RT-PCR products of β-actin mRNA in Hep-3B cells. Lane 1: marker 1500; Lane 2: blank control group; Lane 3: transfection group; Lane4: negative control group.

Figure 6

Figure 6

Electrophoresis of the RT-PCR products of Rab23 mRNA in Hep-3B cells after being silenced by siRNA. Lane 1: blank control group; Lane 2: transfection group; Lane 3: negative control group. a_P_ < 0.05 vs control.

Figure 7

Figure 7

Western blot results for Rab23 in Hep-3B cells after being silenced by siRNA. Lane 1: blank control group; Lane 2: transfection group; Lane 3: negative control group.

Figure 8

Figure 8

Western blot result for Rab23 in Hep-3B cells after being silenced by siRNA. Lane 1: blank control group; Lane 2: transfection group; Lane 3: negative control group. a_P_ < 0.05 vs control.

Figure 9

Figure 9

The results of MTT assays. At 48 h and 72 h, growth of Hep-3B cells was inhibited after being interferenced by siRNA against Rab23 gene. the survival rate of the transfection group decreased compared with controls. P < 0.01 _vs_ control group. Again, there was no significant difference between blank and negative control groups, _P_ > 0.05.

Figure 10

Figure 10

Apoptotic rate of Hep-3B cells measured by flow cytometry. in negative control (A), blank control (B) and transfected (C) groups.

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