COP9 signalosome subunit 5 (CSN5) plays a key role in carcinogenesis of multiple cancers, and contributes to stabilization of target proteins through deubiquitylation. However, the underlying role of CSN5 in thyroid carcinoma has not been reported. In this research, our data showed that CSN5 was overexpressed in thyroid carcinoma tissues compared with para-cancerous tissues. Furthermore, a series of gain/loss functional assays were performed to demonstrate the role of CSN5 in facilitating thyroid carcinoma cell proliferation and metastasis. Additionally, we found that there was a positive correlation between CSN5 and angiopoietin-like protein 2 (ANGPTL2) protein levels in thyroid carcinoma tissues and that CSN5 promoted thyroid carcinoma cell proliferation and metastasis through ANGPTL2. We also identified the underlying mechanism that CSN5 elevated ANGPTL2 protein level through directly binding it, and decreasing its ubiquitination and degradation. Overall, our results highlight the significance of CSN5 in promoting thyroid carcinoma carcinogenesis and implicate CSN5 as a promising candidate for thyroid carcinoma treatment.
Kidney renal clear cell carcinoma (KIRC) is a common and invasive subtype of renal tumors, which has poor prognosis and high mortality. MND1 is a meiosis specific protein that participates in the progress of diverse cancers. Nonetheless, its function in KIRC was unclear. Here, TIMER, TCGA, GEO databases and IHC found MND1 expression is upregulated in KIRC, leading to poor overall survival, and MND1 can serve as an independent prognostic factor. Moreover, enrichment analysis revealed the functional relationship between MND1 and cell cycle, immune infiltration. EdU and transwell assays confirmed that MND1 knockdown surely prohibited the proliferation, migration, and invasion of KIRC cells. Additionally, immune analysis showed that MND1 displayed a strong correlation with various immune cells. Interference with MND1 significantly reduces the expression of chemokines. TCGA and GEO databases indicated that MND1 expression is significantly related to two m6A modification related gene (METTL14, IGF2BP3). Finally, the drug sensitivity analysis revealed 7 potentially sensitive drugs for KIRC patients with high MND1 expression. In conclusion, MND1 can be used as a prognostic biomarker for KIRC and provides clues regarding cell cycle, immune infiltrates and m6A. Sensitive drugs may be an effective treatment strategy for KIRC patients with high expression of MND1.
Hepatocellular carcinoma (HCC) is one of the most deadly and common malignant cancers around the world, and the prognosis of HCC patients is not optimistic. ZNF320 belongs to Krüppel like zinc finger gene family. However, no studies have focused on the influence of ZNF320 in HCC. We first analyzed ZNF320 expression in HCC by using data from TCGA and ICGC, then conducted a joint analysis with TIMER and UALCAN, and validated by immunohistochemistry in clinical HCC samples. Then we applied UALCAN to explore the correlation between ZNF320 expression and clinicopathological characteristics. Consequently, using Kaplan-Meier Plotter analysis and the Cox regression, we can predict the prognostic value of ZNF320 for HCC patients. Next, the analysis by GO, KEGG, and GSEA revealed that ZNF320 was significantly correlated to cell cycle and immunity. Finally, TIMER and GEPIA analysis verified that ZNF320 expression is closely related to tumor infiltrating immune cells (TIIC), including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. The analysis of the TCGA and ICGC data sets revealed that ZNF320 expression was significantly correlated with m6A related genes (RBMX, YTHDF1, and METTL3). In conclusion, ZNF320 may be a prognostic biomarker related to immunity as a candidate for liver cancer.
Deubiquitinating enzyme OTU domain‐containing ubiquitin aldehyde‐binding proteins 1 (OTUB1) has been shown to have an essential role in multiple carcinomas. However, the function of OTUB1 in papillary thyroid cancer (PTC) and the underlying mechanisms regulating PTC cells proliferation remain poorly understood. In this study, OTUB1 was significantly upregulated in papillary thyroid carcinoma tissues and cells. Through in vitro and in vivo experiments, knockdown of OTUB1 suppressed PTC cells growth whereas OTUB1 overexpression enhanced the proliferation ability of PTC cells. Moreover, the eyes absent homologue 1 (EYA1) was recognized as a potential target of OTUB1 through mass spectrometry analysis, and we further verified that EYA1 protein level was positively correlated with OTUB1 expression in PTC cells and clinical samples. Mechanistically, OTUB1 could interact with EYA1 directly and deubiquitinate EYA1 to stabilize it. At last, EYA1 was found to play an essential role in OTUB1‐derived PTC cells growth. Overall, our investigation reveals that OTUB1 is a previously unrecognized oncogenic factor in PTC cells proliferation and suggests that OTUB1 might be a novel therapeutic target in PTC.
Background: Hepatocellular carcinoma represents the most common primary malignancy of all liver cancer types and its prognosis is usually unsatisfactory. TSEN54 encodes a protein constituting a subunit of the tRNA splicing endonuclease heterotetramer. Previous researches concentrated on the contribution of TSEN54 in pontocerebellar hypoplasia, but no studies have yet reported its role in HCC.
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