DJ-1 knockdown inhibits growth and xenograft‑induced tumor generation of human hepatocellular carcinoma cells.
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.
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Shunfang
S
Liu
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Guoxian
G
Long
Department of Nephrology, Puai Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Honglan
H
Wei
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Lei
L
Shi
Department of General Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Zhifang
Z
Yang
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Dongbo
D
Liu
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Guoqing
G
Hu
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Hong
H
Qiu
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D000071617:Protein Deglycase DJ-1; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human