Tripartite Motif Containing 11 Interacts with DUSP6 to Promote the Growth of Human Osteosarcoma Cells through Regulating ERK1/2 Pathway

Abstract

Tripartite Motif Containing 11 (TRIM11), an E3 ubiquitin ligase, is identified as a carcinogen causing certain human cancers. However, the specific role of TRIM11 is still uncovered in human osteosarcoma (OS) cells. To explore the role of TRIM11 in OS cells, TRIM11 was induced by silencing and overexpression in OS cells using RNA interference (RNAi) and lentiviral vector, respectively. qRT-PCR and western blot were used to examine the transcription and translation levels of the target gene. Cell count kit-8 (CCK-8) assays were established to analyze cell proliferation. Cell apoptosis ratio was determined via flow cytometry. In our analyses, TRIM11 was suggested to be upregulated, and it functioned as a pro-proliferation and antiapoptosis factor in OS cells. Moreover, the extracellular-signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 was used to examine the relationship between TRIM11 and ERK1/2 in OS cells. Results demonstrated that the role of TRIM11 was significantly disrupted by the ERK1/ 2 inhibitor PD98059. Interestingly, we found TRIM11 overexpression did not affect dual-specificity phosphatase 6 (DUSP6) transcription, but improved its translation in OS cells. Co-immunoprecipitation (Co-IP) analyses revealed that TRIM11 interacted with DUSP6. Importantly, overexpression of TRIM11 enhanced DUSP6 ubiquitination in OS cells. erefore, TRIM11 might suppress the translation of DUSP6 via improving its ubiquitination. Additionally, TRIM11 silencing in OS cells significantly reduced its tumorigenicity in vivo. Overall, our findings firstly revealed that TRIM11 was an oncogene gene in the growth of OS cells and illustrated its potential function as a target in the treatment of OS.

Structural insights into the viral proteins binding by TRIM7 reveal a general C-terminal glutamine recognition mechanism

“…S5b ). The potential explanation is that these proteins could possibly interact with TRIM7 either through additional binding partners or a different interface 24,25 . Taken together, these results indicate that the glutamine-end motif binding mechanism is a common, albeit potentially not the only, target recognition strategy of TRIM7 for both human and viral proteins.…”

Prediction of Prognosis and Immunotherapy of Osteosarcoma Based on Necroptosis-Related lncRNAs

“…Apparently, AL391121.1 and AL354919.2 are positively regulated by TRIM11 and CD40, respectively. In addition, Wang et al reported that TRIM11 was an oncogene gene in the growth of OS cells ( Wang et al, 2019) . CD40 plays an important role in tumor immunotherapy ( Elgueta et al, 2009 ).…”

Protein Stability Regulation in Osteosarcoma: The Ubiquitin-like Modifications and Glycosylation as Mediators of Tumor Growth and as Targets for Therapy

“…Similar results have been obtained when targeting members of the TRIM family of E3 ligases. TRIM11 silencing leads to ERK activation and reduced cell growth in vitro [ 72 ], whereas targeting TRIM66, both in vivo and in vitro, causes Transforming growth factor-beta (TGF-β) pathway activation, cell cycle inhibition, and apoptosis induction [ 73 ]. TRIM46 negatively regulates PPARα and can induce apoptosis inhibition in vitro [ 74 ].…”