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BACKGROUND Herein, we found that tripartite motif-containing 48 (TRIM48) was reduced in human glioblastoma (GBM) cell lines. We investigated whether and how TRIM48 functions in human GBM in vitro. MATERIAL AND METHODS Human GBM cells (U87 MG and U138 MG) were infected with lentivirus to overexpress TRIM48, and 1 human GBM cell line (T98G) was infected with siRNAs to knock down TRIM48 expression. Techniques used included cell proliferation assay, measured by CCK-8 and BrdU-ELISA method, and cell cycle assay, determined using flow cytometry. Curcumin, a specific activator of extracellular signal regulated kinases (ERK1/2), or PD98059, a specific inhibitor of ERK1/2, was used to activate or block the ERK1/2 pathway, respectively. Expression of phosphorylated (p)-ERK1/2, and its downstream targets (Cyclin D1) were measured to assess the mechanism. RESULTS Our data suggest that overexpression of TRIM48 reduces the viability of U87 MG and U138 MG and leads to cell cycle arrest (in G0-G1 phase), which is associated with blockade of the ERK1/2 pathway and reduction of Cyclin D1. In contrast, knockdown of TRIM48 resulted in the opposite effects. Interestingly, the inhibitory effect of TRIM48 overexpression on human GBM cell growth and the inactivation of ERK1/2 were significantly alleviated with additional curcumin treatment, while it the promoted the effect of siTRIM48 on human GBM cell growth, and the activation of ERK1/2 was significantly alleviated with additional PD98059 treatment. CONCLUSIONS TRIM48 suppressed the growth of human GBM cell via the prevention of ERK1/2 activation.
This article was published in the following journal.
Name: Medical science monitor : international medical journal of experimental and clinical research
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A tripartite motif protein consisting of an N-terminal RING finger, two B-box type ZINC FINGERS, and C-terminal PHD domain. It functions as a transcriptional repressor by associating with Kruppel-association box domain (KRAB domain) transcription factors and has E3-SUMO-ligase activity towards itself and also sumoylates INTERFERON REGULATORY FACTOR-7 to reduce its activity as a transcriptional activator. It can also function as a ubiquitin protein ligase towards TUMOR SUPPRESSOR PROTEIN P53.
Retrovirus-associated DNA sequences (v-sis) originally isolated from the simian sarcoma virus (SSV). The proto-oncogene c-sis codes for a growth factor which is the B chain of PLATELET-DERIVED GROWTH FACTOR. v-sis or overexpression of c-sis causes tumorigenesis. The human sis gene is located at 22q12.3-13.1 on the long arm of chromosome 22.
A protein interaction domain that is characterized by a bent "beta-sandwich" consisting of two antiparallel beta-sheets. It occurs in eukaryotic proteins, including many TRIPARTITE MOTIF PROTEINS, which function in a variety of cellular processes.
A protein family defined by the presence of three ZINC FINGER domains, one of which is a RING FINGER DOMAIN, a coiled-coil region, and a highly variable C-terminal region. They function in many cellular processes including APOPTOSIS and CELL CYCLE regulation.
A species of Bifidobacterium that occurs in the human GASTROINTESTINAL TRACT and VAGINA. It inhibits the growth of pathogenic bacteria, may modulate the immune response, and is used as a PROBIOTIC.
An assay is an analytic procedure for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity. This can be a drug or biochemical substance or a cell in an organism or organic sample. ...
Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...