DJ-1 knockdown inhibits growth and xenograft‑induced tumor generation of human hepatocellular carcinoma cells

Liu,Shunfang; Long,Guoxian; Wei,Honglan; Shi,Lei; Yang,Zhifang; Liu,Dongbo; Hu,Guoqing; Qiu,Hong

doi:10.3892/or.2014.3594

January-2015 Volume 33 Issue 1

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January-2015 Volume 33 Issue 1

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Article

DJ-1 knockdown inhibits growth and xenograft‑induced tumor generation of human hepatocellular carcinoma cells

Authors:
- Shunfang Liu
- Guoxian Long
- Honglan Wei
- Lei Shi
- Zhifang Yang
- Dongbo Liu
- Guoqing Hu
- Hong Qiu
View Affiliations / Copyright

Affiliations: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Nephrology, Puai Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China, Department of General Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Pages: 201-206
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Published online on: November 7, 2014

https://doi.org/10.3892/or.2014.3594
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Abstract

The aim of this study was to identify potential downstream effectors of the oncogene DJ-1 in hepatocellular carcinoma (HCC) cell lines, and examine its role in the Akt signaling pathway and HCC oncogenesis. Expression of the DJ-1 protein was assessed by immunoblotting in several human HCC cell lines. Knockdown of DJ-1 was achieved by transfecting DJ-1-specific short hairpin RNAs into the HepG2 HCC cell line. The effect of DJ-1 downregulation on phosphatase and tensin homolog (PTEN) and phosphorylated Akt was evaluated. In addition, cell cycle, proliferation, adhesion and invasion were analyzed in the DJ-1 knockdown of HepG2 cells. The growth of HepG2‑induced tumor was evaluated in a nude mouse model after DJ-1 silencing. Stable DJ-1 knockdown was achieved in HepG2 cells using a shRNA eukaryotic expression vector. Downregulation of DJ-1 increased PTEN expression but decreased phosphorylation of Akt in HepG2 cells. In addition, DJ-1 knockdown resulted in the decreased proliferation, adhesion and invasion of HepG2 cells in vitro, and inhibited the growth of HepG2-induced tumor in vivo. DJ-1 knockdown altered the malignant behavior of HepG2 cells, potentially through the Akt signaling pathway, suggesting a crucial role for DJ-1 in the oncogenesis of HCC.

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1	Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar : PubMed/NCBI
2	Giannelli G and Antonaci S: Novel concepts in hepatocellular carcinoma: from molecular research to clinical practice. J Clin Gastroenterol. 40:842–846. 2006. View Article : Google Scholar : PubMed/NCBI
3	Sherman M: Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis. Semin Liver Dis. 30:3–16. 2010. View Article : Google Scholar : PubMed/NCBI
4	Rahbari NN, Mehrabi A, Mollberg NM, et al: Hepatocellular carcinoma: current management and perspectives for the future. Ann Surg. 253:453–469. 2011. View Article : Google Scholar : PubMed/NCBI
5	Adachi E, Maehara S, Tsujita E, et al: Clinicopathologic risk factors for recurrence after a curative hepatic resection for hepatocellular carcinoma. Surgery. 131(Suppl 1): S148–S152. 2002. View Article : Google Scholar : PubMed/NCBI
6	Diamantis A, Magiorkinis E, Sakorafas GH and Androutsos G: A brief history of apoptosis: from ancient to modern times. Onkologie. 31:702–706. 2008. View Article : Google Scholar : PubMed/NCBI
7	Fabregat I: Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol. 15:513–520. 2009. View Article : Google Scholar : PubMed/NCBI
8	Schulze-Bergkamen H and Krammer PH: Apoptosis in cancer - implications for therapy. Semin Oncol. 31:90–119. 2004. View Article : Google Scholar : PubMed/NCBI
9	Mo JS, Kim MY, Ann EJ, Hong JA and Park HS: DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death. Cell Death Differ. 15:1030–1041. 2008. View Article : Google Scholar : PubMed/NCBI
10	Junn E, Taniguchi H, Jeong BS, Zhao X, Ichijo H and Mouradian MM: Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc Natl Acad Sci USA. 102:9691–9696. 2005. View Article : Google Scholar : PubMed/NCBI
11	Yuen HF, Chan YP, Law S, et al: DJ-1 could predict worse prognosis in esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 17:3593–3602. 2008. View Article : Google Scholar : PubMed/NCBI
12	Davidson B, Hadar R, Schlossberg A, et al: Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma. Hum Pathol. 39:87–95. 2008. View Article : Google Scholar
13	Zhang HY, Wang HQ, Liu HM, Guan Y and Du ZX: Regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by DJ-1 in thyroid cancer cells. Endocr Relat Cancer. 15:535–544. 2008. View Article : Google Scholar : PubMed/NCBI
14	Hod Y: Differential control of apoptosis by DJ-1 in prostate benign and cancer cells. J Cell Biochem. 92:1221–1233. 2004. View Article : Google Scholar : PubMed/NCBI
15	MacKeigan JP, Clements CM, Lich JD, Pope RM, Hod Y and Ting JP: Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: identification of RS/DJ-1 and RhoGDIα. Cancer Res. 63:6928–6934. 2003.PubMed/NCBI
16	Kim RH, Peters M, Jang Y, et al: DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell. 7:263–273. 2005. View Article : Google Scholar : PubMed/NCBI
17	Zhang D, Lim SG and Koay ES: Proteomic identification of down-regulation of oncoprotein DJ-1 and proteasome activator subunit 1 in hepatitis B virus-infected well-differentiated hepatocellular carcinoma. Int J Oncol. 31:577–584. 2007.PubMed/NCBI
18	Das R, Mahabeleshwar GH and Kundu GC: Osteopontin stimulates cell motility and nuclear factor κB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem. 278:28593–28606. 2003. View Article : Google Scholar : PubMed/NCBI
19	McManus MT and Sharp PA: Gene silencing in mammals by small interfering RNAs. Nat Rev Genet. 3:737–747. 2002. View Article : Google Scholar : PubMed/NCBI
20	Wang SL, Yao HH and Qin ZH: Strategies for short hairpin RNA delivery in cancer gene therapy. Expert Opin Biol Ther. 9:1357–1368. 2009. View Article : Google Scholar : PubMed/NCBI
21	Romashkova JA and Makarov SS: NF-κB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 401:86–90. 1999. View Article : Google Scholar : PubMed/NCBI
22	Li Y, Tang ZY, Ye SL, et al: Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol. 7:630–636. 2001.
23	Song MS, Salmena L and Pandolfi PP: The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 13:283–296. 2012.PubMed/NCBI
24	Sun H, Lesche R, Li DM, et al: PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc Natl Acad Sci USA. 96:6199–6204. 1999. View Article : Google Scholar : PubMed/NCBI
25	Mitsiades CS, Mitsiades N and Koutsilieris M: The Akt pathway: molecular targets for anti-cancer drug development. Curr Cancer Drug Targets. 4:235–256. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

DJ-1 knockdown inhibits growth and xenograft‑induced tumor generation of human hepatocellular carcinoma cells

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Abstract

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