Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDH Inhibits Cell Growth and Induces Apoptosis by Regulating the PTEN/AKT Pathway in Hepatocellular Carcinoma.
The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin(MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles of MTDH with regard to growth and apoptosis in HCC have not yet been studied. In the present study, we first analyzed the expression of MTDH in HCC samples. We found that MTDH protein levels are higher in most HCC cancerous tissues compared with their matched adjacent non-tumor tissues. Additionally, the MTDH mRNA was also higher inHCC tissues compared to their matched adjacent non-tumor tissues. Knockdown of the endogenous MTDH using small interfering RNA further showed that deficiency of MTDH suppressed cell growth and caused apoptosis in HCC cells. Knockdown MTDH promoted PTEN and p53 expression in HCC cells and inhibited AKT phosphorylation. Knockdown MTDH also inhibited tumor growth in vivo. All these results indicated that MTDH protein levels in most HCC tissues are higher than non-tumor tissues, and knockdown of MTDH inhibited growth and induced apoptosis in HCC cells through the activation of PTEN.Therefore, MTDH might be an effective targeted therapy gene for HCC.
Department of Hepatibiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. wen_fang79@yahoo.com.
Wen-Fang
WF
Li
Department of Cancer Research Center, Hubei Medical University, Shiyan 442000, China. ouqinzaisy@sina.com.
Qin
Q
Ou
Department of Hepatibiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. hangdaicq@sina.com.
Hang
H
Dai
Department of Hepatibiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. chang_an_liu@yahoo.com.|State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Shiyan 442000, China. chang_an_liu@yahoo.com.
Chang-An
CA
Liu
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D049109:Cell Proliferation; D056945:Hep G2 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D016601:RNA-Binding Proteins; D000067492:RNAi Therapeutics; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
apoptosis; growth; hepatocellular carcinoma; metadherin