Downregulation of TRIM21 contributes to hepatocellular carcinoma carcinogenesis and indicates poor prognosis of cancers

• Published in: Tumor biology Vol. 36; no. 11; pp. 8761 - 8772
• Main Authors: Ding, Qianshan, He, Du, He, Ke, Zhang, Qian, Tang, Meng, Dai, Jinfen, Lv, Hanlin, Wang, Xiaochen, Xiang, Guoan, Yu, Honggang
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.11.2015; Springer Nature B.V
• Subjects: Adult; Aged; Apoptosis; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinogenesis - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Immunohistochemistry; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Medical prognosis; Middle Aged; Neoplasm Invasiveness - genetics; Prognosis; Research Article; Ribonucleoproteins - biosynthesis; Ribonucleoproteins - genetics; Tumors; Hepatocellular carcinoma; Prognosis; TRIM21; Tumor suppressor; Cancer
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-3572-2

The aim of our work is to clarify the clinical implication and functional role of tripartite motif 21 (TRIM21) in hepatocellular carcinoma (HCC). We validated that TRIM21 was downregulated in liver cancer samples by immunohistochemical (IHC) staining. We also demonstrated that its downregulation was associated with several clinicopathologic features such as tumor numbers, T stage, Barcelona Clinic Liver Cancer (BCLC) stage, and Cancer of the Liver Italian Program (CLIP) stage of HCC patients. Importantly, the expression of TRIM21 in tumor samples is significantly correlated with the prognosis of the patients. We further silenced TRIM21 in HCC cell HepG2 and LM3 and confirmed that TRIM21 silencing will promote cancer cell proliferation (CCK-8 assay), colony forming (plate colony-forming assay), migration (transwell assay), and the ability of antiapoptosis (annexin V-FITC/PI staining) in vitro. Then, we predicted gene sets influenced by TRIM21 by using bioinformatic tools. For the first time, we prove that TRIM21 is a potential tumor suppressor in HCC and its low expression indicates poor prognosis. Our findings provide useful insight into the mechanism of HCC origin and progression and offer clues to novel HCC therapies.