Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway

Yu, Guihua; Li, Aimin; Li, Xiang; Ye, Zhong; Peng, Hao

doi:10.1177/1010428317705572

Cited by 10 publications

(4 citation statements)

References 28 publications

(30 reference statements)

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“…The TRIM family, which contains more than 70 members, has been identified as being involved in the progression, transformation, autophagy, and metastasis of cancer [37][38][39]. TRIM14 belongs to the TRIM protein family, and has been shown to be markedly increased in human osteosarcoma tissues and cell lines and strongly associated with aggressive characteristics and poor patient outcome [10,14,16,40,41]. However, the role played by TRIM14 in glioblastoma has not been completely confirmed.…”

Section: Discussionmentioning

confidence: 99%

Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells

Feng

Cai

et al. 2019

J Exp Clin Cancer Res

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Background: Several members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated. Methods: The expression levels of TRIM14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines. Two independent TRIM14 shRNA were transfected into LN229 and U251 cells, and the effect of TRIM14 depletion was confirmed. Transwell assay and wound healing assay assay were carried out to assess the effect of TRIM14 depletion on glioblastoma cell invasion and migration. Western blotting was performed to screen the downstream gene of TRIM14. The stability analysis and Ubiquitylation assays and Orthotopic xenograft studies were also performed to investigate the role of TRIM14 and the relationship with downstream gene. Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of TRIM14. Results: In this study, we showed that TRIM14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times. Functional experiments showed that decreased TRIM14 expression reduced glioblastoma cell invasion and migration. Furthermore, we identified that zinc finger E-box binding homeobox 2 (ZEB2), a transcription factor involved in epithelial-mesenchymal transition, is a downstream target of TRIM14. Further investigation revealed that TRIM14 inactivation significantly facilitated ZEB2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration. Our findings provide insight into the specific biological role of TRIM14 in tumor invasion.Conclusions: Our findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells

Feng

Cai

et al. 2019

J Exp Clin Cancer Res

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“…TRIM14 was found to regulate cell proliferation and invasion in osteosarcoma via promotion of AKT signaling ( 8 ). Moreover, a bispecific antibody against TRIM14 suppressed osteosarcoma aggressiveness through regulation of the NF-κB signaling pathway ( 25 ). Here, we reported for the first time that TRIM14 mRNA and protein were both increased in GC tissues and cell lines.…”

Section: Discussionmentioning

confidence: 99%

TRIM14 promotes the migration and invasion of gastric cancer by regulating epithelial‑to‑mesenchymal transition via activation of AKT signaling regulated by miR‑195‑5p

et al. 2018

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Tripartite motif-containing 14 (TRIM14) is a member of the TRIM protein family which has been implicated in several critical processes and is dysregulated in human cancers in a cancer-specific trend. However, its expression and function in human gastric cancer (GC) are still largely unknown. In this study, we confirmed for the first time that TRIM14 mRNA and protein were upregulated in GC tissues and cell lines as determined by qRT-PCR and western blot analysis. Clinical data disclosed that high TRIM14 expression was significantly associated with aggressive prognostic features, including advanced TNM stage and lymph node metastasis. In regards to 5-year survival, TRIM14 served as a potential prognostic marker for GC. Notably, TRIM14 promoted migration, invasion as measured by Transwell and epithelial-to-mesenchymal transition (EMT) as determined by western blot analysis and immunofluorescence (IF) in vitro and in vivo. Moreover, TRIM14 induced protein kinase B (AKT) pathway activation, and inhibition of AKT reversed the TRIM14-induced promotive effects on cell migration, invasion and EMT progression. Furthermore, we demonstrated that TRIM14 expression was regulated by miR-195-5p. miR-195-5p exerted an inhibitory role in GC migration and invasion. Finally, we confirmed that alteration of TRIM14 expression abolished the effects of miR-195-5p on GC cells. Conclusively, our results demonstrated that TRIM14 functions as an oncogene in regulating EMT and metastasis of GC via activating AKT signaling, which was regulated by miR-195-5p, supporting its potential utility as a therapeutic target for GC.

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“…In our current study, KEGG analysis detected that ZnO NPs triggered overlapping activation signal pathways (MAPK, NF-κB and TLRs) associated with speci c cellular functions in both types of OS cell lines. The MAPK signaling pathway controls several fundamental biological processes of cells, including cellular growth, proliferation, survival, autophagy [30], Moreover, the NF-κB pathway regulated multiple important cellular functions, especially in ammatory responses, such as interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α), and inhibited the proliferation and metastasis of OS cells [31,32], which were both obviously dowregulated by ZnO NPs. The TLR pathway play crucial roles in many aspects of the innate immune responses through the recognition of speci c conserved pathogen-associated molecular patterns (PAMPs) from various microbes, leading to activation of the interferons or IFNinducible genes and pro-in ammatory cytokines, which participate in tumor immune monitoring and play an important role in tumor growth, resulting in enhancinng antibody-dependent cell-mediated cytotoxicity [33].…”

Section: Discussionmentioning

confidence: 99%

Zinc Oxide Nanoparticles (ZnO NPs) Treated Two Types of Osteosarcoma Cell Lines for Identifying Differentially Expressed Genes

Guo,

Wang,

Yang

et al. 2023

Preprint

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Osteosarcoma (OS) primarily affects in adolescents, and is more prevalent in males than females. It is characteristics by local invasive growth and early pulmonary metastases. Nanoparticles (NPs) have emerged as a promising alternative to traditional chemotherapeutic drugs due to their high selectivity and effectiveness. Previous studies have demonstrated the potential of zinc oxide nanoparticles (ZnO NPs) as a treatment for various tumors except OS. In this study, we use RNA-seq analysis to investigate the underlying biological mechanism involved in the process of ZnO NPs-treated different types of OS cell lines. We identified 928 differentially expressed genes (DEGs) in both 143B and MG-63 cells, and we validated the expression of the eight most significant DEGs using RT-qPCR. Gene Ontology (GO) analysis displayed regulation of transcription factor on nucleic acid binding in molecular function term, and extracellular space in cellular components term in both OS cell lines. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the co-enrichment of the MAPK, Toll-like receptor, and NF-κB pathways in both OS cell lines. Protein-protein interaction (PPI) analysis highlighted the involvement of HMOX1, MAFB, CXCL10, and CXCL11 in various biological processes in OS cells treated with ZnO NPs. Furthermore, we confirmed the key protein molecules in the differential signaling pathways of both OS cell lines using Western Blot (WB). Our findings shed light on the potential antitumor mechanisms and exploitable bioeffects of ZnO NPs in the treatment of OS. This study provides more targets and possible mechanisms for the treatment of ZnO NPs, as well as more theoretical basis for the treatment of OS.

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Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway

Cited by 10 publications

References 28 publications

Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells

Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells

TRIM14 promotes the migration and invasion of gastric cancer by regulating epithelial‑to‑mesenchymal transition via activation of AKT signaling regulated by miR‑195‑5p

Zinc Oxide Nanoparticles (ZnO NPs) Treated Two Types of Osteosarcoma Cell Lines for Identifying Differentially Expressed Genes

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