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.
Figures
Figure 1
In situ hybridization using tissue microarrays.
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
Expression of Rab23 in normal liver tissues and HCCs as seen by immunohistochemistry (A-C) and in situ hybridization (D-F).
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
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
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
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
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
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
Apoptotic rate of Hep-3B cells measured by flow cytometry. in negative control (A), blank control (B) and transfected (C) groups.
Similar articles
- MiR-429 regulates the metastasis and EMT of HCC cells through targeting RAB23.
Xue H, Tian GY. Xue H, et al. Arch Biochem Biophys. 2018 Jan 1;637:48-55. doi: 10.1016/j.abb.2017.11.011. Epub 2017 Dec 2. Arch Biochem Biophys. 2018. PMID: 29191386 - Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway.
Liu SJ, Zang YW, Huang CJ, Liu YJ. Liu SJ, et al. Cancer Rep (Hoboken). 2024 Jan;7(1):e1921. doi: 10.1002/cnr2.1921. Epub 2023 Oct 26. Cancer Rep (Hoboken). 2024. PMID: 37884351 Free PMC article. - IGF2 Is Up-regulated by Epigenetic Mechanisms in Hepatocellular Carcinomas and Is an Actionable Oncogene Product in Experimental Models.
Martinez-Quetglas I, Pinyol R, Dauch D, Torrecilla S, Tovar V, Moeini A, Alsinet C, Portela A, Rodriguez-Carunchio L, Solé M, Lujambio A, Villanueva A, Thung S, Esteller M, Zender L, Llovet JM. Martinez-Quetglas I, et al. Gastroenterology. 2016 Dec;151(6):1192-1205. doi: 10.1053/j.gastro.2016.09.001. Epub 2016 Sep 7. Gastroenterology. 2016. PMID: 27614046 - Sublocalization of Rab23, a mediator of Sonic hedgehog signaling pathway, in hepatocellular carcinoma cell lines.
Sun HJ, Liu YJ, Li N, Sun ZY, Zhao HW, Wang C, Li H, Ma FM, Shi SM, Xu XQ, Chen ZY, Huang SH. Sun HJ, et al. Mol Med Rep. 2012 Dec;6(6):1276-80. doi: 10.3892/mmr.2012.1094. Epub 2012 Sep 20. Mol Med Rep. 2012. PMID: 23007279 - Rab23's genetic structure, function and related diseases: a review.
Zheng LQ, Chi SM, Li CX. Zheng LQ, et al. Biosci Rep. 2017 Mar 2;37(2):BSR20160410. doi: 10.1042/BSR20160410. Print 2017 Apr 30. Biosci Rep. 2017. PMID: 28104793 Free PMC article. Review.
Cited by
- MicroRNA-367-3p directly targets RAB23 and inhibits proliferation, migration and invasion of bladder cancer cells and increases cisplatin sensitivity.
Wei X, Jiang Y, Yang G, Chang T, Sun G, Chen S, Wu S, Liu R. Wei X, et al. J Cancer Res Clin Oncol. 2023 Dec;149(20):17807-17821. doi: 10.1007/s00432-023-05484-6. Epub 2023 Nov 8. J Cancer Res Clin Oncol. 2023. PMID: 37935937 Free PMC article. - Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in Preclinical In Vivo Models.
Weidle UH, Nopora A. Weidle UH, et al. Cancer Genomics Proteomics. 2023 Nov-Dec;20(6):500-521. doi: 10.21873/cgp.20401. Cancer Genomics Proteomics. 2023. PMID: 37889063 Free PMC article. Review. - TPI1-reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis.
Liu BHM, Tey SK, Mao X, Ma APY, Yeung CLS, Wong SWK, Ng TH, Xu Y, Yao Y, Fung EYM, Tan KV, Khong PL, Ho DW, Ng IO, Tang AHN, Cai SH, Yun JP, Yam JWP. Liu BHM, et al. J Extracell Vesicles. 2021 Aug;10(10):e12135. doi: 10.1002/jev2.12135. Epub 2021 Aug 11. J Extracell Vesicles. 2021. PMID: 34401050 Free PMC article. - Rab23 contributes to the progression of colorectal cancer via protein kinase B and extracellular signal-regulated kinase signaling pathways.
Zhao T, Han D, Meng H. Zhao T, et al. Oncol Lett. 2019 Aug;18(2):1793-1799. doi: 10.3892/ol.2019.10491. Epub 2019 Jun 18. Oncol Lett. 2019. PMID: 31423247 Free PMC article. - Rab23 Promotes Hepatocellular Carcinoma Cell Migration Via Rac1/TGF-β Signaling.
Zhang L, Zhang B, You W, Li P, Kuang Y. Zhang L, et al. Pathol Oncol Res. 2020 Jan;26(1):301-306. doi: 10.1007/s12253-018-0463-z. Epub 2018 Sep 6. Pathol Oncol Res. 2020. PMID: 30191377
References
- Iimuro Y, Fujimoto J. Strategy of gene therapy for liver cirrohosis and hepatocellular carcinoma. J Hepatobiliary Pancreat Surg. 2003;10:45–47. - PubMed
- Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004;432:324–331. - PubMed
- Clatworthy JP, Subramanian V. Stem cells and the regulation of proliferation, differentiation and patterning in the intestinal epithelium: emerging insights from gene expression patterns, transgenic and gene ablation studies. Mech Dev. 2001;101:3–9. - PubMed
- Ruiz i Altaba A, Sánchez P, Dahmane N. Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer. 2002;2:361–372. - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases