Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53

• Published in: Cellular physiology and biochemistry Vol. 44; no. 1; pp. 255 - 266
• Main Authors: Liu, Jinjin, Rao, Jun, Lou, Xuming, Zhai, Jian, Ni, Zhenhua, Wang, Xiongbiao
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2017
• Subjects: Animals; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Movement; Cell Proliferation; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Down-Regulation; Epithelial-Mesenchymal Transition; HCC; Hep G2 Cells; Humans; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Mice; Mice, Inbred BALB C; Mice, Nude; Original Paper; P53; Progression; Real-Time Polymerase Chain Reaction; RNA Interference; RNA, Small Interfering - metabolism; Transplantation, Heterologous; Trim11; Tripartite Motif Proteins - antagonists & inhibitors; Tripartite Motif Proteins - genetics; Tripartite Motif Proteins - metabolism; Tumor growth; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Ubiquitin-Protein Ligases - antagonists & inhibitors; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Up-Regulation; Progression; HCC; Tumor growth; Trim11; P53
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000484678

Background/Aims: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). Methods: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. Results: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss- and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. Conclusions: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment.