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

Abstract

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.

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

“…Trim family proteins play an important role in cell proliferation, migration, differentiation, and apoptosis (39)(40)(41). Studies have found that Trim11 promotes hepatoma cell proliferation, migration, and invasion and epithelial-tomesenchymal transition and tumor growth in vivo (42). Trim11 also promotes cell proliferation and inhibits cell apoptosis in colon cancer (43).…”

Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer

“…Depletion of Dear1 increased Smad3 levels of downstream effectors Snail1 and Snail2 [ 94 , 153 ]. Many T Trim proteins have been shown to be up-regulated in different cancer tissues and to be related to the EMT process [ 154 , 155 , 156 , 157 ]. However, the exact mechanism by which they influence EMT is not well-known, although there is an increasing amount of evidence that suggests that it is not related to their ubiquitin-ligase activity.…”

Targeting Chemoresistant Tumors: Could TRIM Proteins-p53 Axis Be a Possible Answer?

“…Later, overexpression of TRIM11 was found in high-grade gliomas, lung cancer, liver and pancreatic cancer with an oncogenic function promoting cell growth, migration, invasion and chemoresistance, suggesting TRIM11 as a novel target for tumour treatment [85]. This oncogenic function is due to the action of TRIM11 in promoting p53 down-regulation with repercussions on p53 downstream pathways [61].…”