Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation
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PROVIDER: PRJNA670655 | ENA |
REPOSITORIES: ENA
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Project description:Glioma is characterized by high migration and invasion, and the relative molecular mechanism is still poor. Accumulating studies demonstrated that ubiquitin specific protease 39 (USP39) played an oncogenic role in several cancers. Here, we investigate USP39 expression and function in human glioma. Oncomine database analysis revealed high USP39 expression in glioma and elevated USP39 expression correlated significantly with poor overall survival. Knockdown of USP39 significantly inhibited the migration and invasion of U251 and U87 cells. The gene expression profile was executed to screen the target molecules of USP39. The result showed that ADAM9, a molecule involved in migration and invasion of various human tumors, was significantly downregulated in the U251 and U87 cells with shRNA-mediated USP39 knockdown. Mechanistically, USP39 directly interacted with the ADAM9 mRNA and induced ADAM9 mRNA maturation, following the decreased expression of integrin β1. Besides, overexpressed ADAM9 rescued the inhibited migration and invasion of glioma cells causing by USP39 depletion. USP39 promoted invasion in vivo and reduced the overall survival of the mice. Collectively, USP39 may have oncogenic role that increase ADAM9 protein levels by inducing maturation of ADAM9 mRNA in glioma. USP39 could be considered a new potential therapeutic target for glioma.
2020-10-23 | GSE159823 | GEO
Project description:Glioma cells are characterized by high migration and invasion ability; however, the molecular mechanism behind both processes still remains to be investigated. Several studies have demonstrated that ubiquitin-specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression was significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with short hairpin RNA (shRNA) against USP39 revealed that disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Furthermore, USP39 induced ADAM9 messenger RNA (mRNA) maturation and decreased the expression of integrin β1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data show that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered potential target for treating patients with glioma.
| S-EPMC8763660 | biostudies-literature
Project description:Effect of expression of dipeptidyl peptidase-IV (DPP-IV) in U373 cell line on uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix.
2011-12-31 | E-MTAB-583 | biostudies-arrayexpress
Project description:UBA1 is the primary E1 ubiquitin-activating enzyme, regulating stability and function of numerous proteins via initiating their ubiquitination. Decreased or insufficient ubiquitination can cause or drive aging and many deadly diseases. Therefore, a small-molecule UBA1 activity enhancer could have broad therapeutic potential. Here we report that auranofin, a drug approved for the treatment of rheumatoid arthritis is a potent UBA1 activity enhancer. Auranofin binds to the UBA1’s ubiquitin fold domain in vitro with a KD of 5.19 nM. The binding enhances UBA1 interactions with at least 20 different E2 ubiquitin-conjugating enzymes, facilitating ubiquitin charging to E2 and increasing the activities of five representative E3s in vitro. Auranofin promotes ubiquitination and degradation of misfolded ER proteins during ER-associated degradation in cells at low nanomolar concentrations. It also facilitates outer mitochondrial membrane-associated degradation. This study discovered the first small-molecule UBA1 activity enhancer, providing a much-needed tool for UBA1 research and therapeutic exploration.
2023-07-10 | PXD042558 | Pride
Project description:BACKGROUND:Ubiquitin specific peptidase 39 (USP39), an essential factor in the assembly of the mature spliceosome complex, has an aberrant expression in several cancer. However, its function and the corresponding mechanism on human osteosarcoma has not been fully explored yet. METHODS:The mRNA and DNA copies of USP39 were increased in osteosarcoma cancer tissues compared with the one in human normal tissues according to datasets from the publicly available Oncomine database. A further western blot analysis also demonstrated an aberrant endogenous expression of USP39 in three different osteosarcoma cells. Then lentivirus-mediated short hairpin RNA (shRNA) was designed to silence USP39 in human osteosarcoma cell line U2OS, which is used to test the impact of USP39-silencing on cellular proliferation, colony formation, cell cycle distribution and apoptosis. RESULTS:Knockdown of USP39 expression in U2OS cell significantly decreased cell proliferation, impaired colony formation ability. A further analysis indicated suppression of USP39 arrested cell cycle progression at G2/M phase via p21 dependent way. In addition, the results of Annexin V/7-AAD staining suggested the knockdown of USP39 could promote U2OS cell apoptosis through PARP cleavage. CONCLUSIONS:These results uncover the critical role of USP39 in regulating cancer cell mitosis and indicate USP39 is critical for osteosarcoma tumorigenesis.
| S-EPMC5389082 | biostudies-literature
Project description:Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs
| PRJEB34627 | ENA
Project description:Ubiquitin-specific peptidase 39 (USP39) has been reported to participate in the mitotic spindle checkpoint and the process of cytokinesis. and has been identified as a therapeutic target for various types of cancer. However, the effect of USP39 in colorectal cancer (CRC) has not been investigated. To explore the functional role of USP39 in CRC cell growth, lentivirus-mediated RNA interference was applied to inhibit USP39 expression in SW1116 and HCT116 cells. The relative USP39 mRNA and protein expression levels were significantly reduced in the USP39 knockdown cells, as verified by reverse transcription-quantitative polymerase chain reaction and western blot analysis. USP39 knockdown significantly reduced the proliferation and colony formation abilities of CRC cells, and induced apoptosis and cell cycle arrest in the G2/M phases, as determined by an MTT assay, a colony formation assay and flow cytometry analysis. Furthermore, western blot analysis demonstrated that USP39 knockdown may have induced apoptosis through the upregulation of p53, p-p53, PARP and caspase-3 expression in SW1116 cells. In conclusion, USP39 may be a novel biological marker for targeted therapy against CRC, and requires further investigation.
| S-EPMC5844003 | biostudies-literature
Project description:Leishmania donovani Ld 39 strain:Ld 39 Genome sequencing and assembly
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| PRJNA915925 | ENA