Topics

SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3.

08:00 EDT 12th June 2019 | BioPortfolio

Summary of "SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3."

Renal cell carcinoma (RCC) is one of the common lethal urologic tumors. Recent studies revealed that SIRT1 might function as a tumor suppressor during the progression of RCC. In addition, studies showed that FGB expression was abnormally upregulated in RCC and related to the progress of RCC. This study aimed to define the function of SIRT1 and underlying mechanism in the RCC progression. The expression of SIRT1 and FGB in RCC specimens and cells were detected by immunoblotting and immunostaining. Luciferase reporter assay was performed to confirm FGB as the target gene of STAT3. Other methods including stable transfection, co-immunoprecipitation, Western blot, and in vitro and in vivo proliferation assays were also performed. Our results showed that SIRT1 expression was downregulated in RCC tissues compared to adjacent normal tissues and relatively high expression of SIRT1 conferred a better prognosis for patients. Next, we showed that SIRT1 overexpression inhibited RCC tumorigenesis both in vitro and in vivo. In addition, FGB expression was upregulated in RCC tissues and overexpressing SIRT1 reduced FGB expression levels. Furthermore, inhibition of RCC proliferation by SIRT1 overexpression was rescued by FGB overexpression, indicating that SIRT1 inhibited RCC proliferation by repressing FGB expression. Mechanistically, we confirmed that FGB was the target gene of STAT3, and SIRT1 repressed the expression of FGB by deacetylation of STAT3, leading to STAT3 destabilization and degradation. SIRT1 inhibited RCC tumorigenesis by downregulating FGB expression, and this novel SIRT1-STAT3-FGB axis provided a potential target for RCC therapy.

Affiliation

Journal Details

This article was published in the following journal.

Name: Experimental cell research
ISSN: 1090-2422
Pages:

Links

DeepDyve research library

PubMed Articles [12262 Associated PubMed Articles listed on BioPortfolio]

Differential expression of miRNAs regulating NF-κB and STAT3 crosstalk during colitis-associated tumorigenesis.

Inflammatory bowel disease (IBD) is mostly responsible for the development of colitis-associated colon cancer. Of the several signaling pathways involved in colonic inflammation, the activation and cr...

Let-7f-5p suppresses Th17 differentiation via targeting STAT3 in multiple sclerosis.

T helper 17 (Th17) cells are regarded as key factors in the pathogenesis of multiple sclerosis (MS). Although the involvement of certain microRNAs (miRNAs) in the development of MS has been reported, ...

SIRT1 activation attenuates cardiac fibrosis by endothelial-to-mesenchymal transition.

Endothelial-to-mesenchymal transition (EndMT) is closely related to the pathogenesis of various diseases, including cardiac fibrosis. Transforming growth factor (TGF)-β1 strongly induces EndMT, and s...

Deacetylation of β-catenin by SIRT1 regulates self-renewal and oncogenesis of liver cancer stem cells.

Hepatocellular carcinoma (HCC) is a highly malignant liver tumor. The presence of cancer stem cells (CSCs) figures prominently in tumor invasion, therapeutic resistance and tumor recurrence resulting ...

LncRNA MST1P2/miR-133b axis affects the chemoresistance of bladder cancer to cisplatin-based therapy via Sirt1/p53 signaling.

Although bladder cancer is commonly chemosensitive to standard first-line therapy, the acquisition of the resistance to cisplatin (DDP)-based therapeutic regimens remains a huge challenge. Noncoding R...

Clinical Trials [2494 Associated Clinical Trials listed on BioPortfolio]

The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure

The purpose of this study is to find out the possible relationship among TWEAK/Fn14, JAK/STAT3 and IDO as well as their roles in the dysfunction of immune micro-environment of endometrium ...

Role of SIRT1 in Regulation of Epithelial-to-mesenchymal Transition in Breast Cancer Lymph Nodes Metastasis

Luminal A breast cancer is a kind of breast cancer with low rate lymph node metastasis and good survival. But in clinical practice, Luminal A breast cancer can present with early, unexpect...

Impact of P53 and SIRT1 in Type 2 Diabetes

Investigating the impact of p53 and SIRT1 in the development of type 2 DM

The Role of Aromatic Hydrocarbon Receptor in the Tumorigenesis of Neuroblastoma and Its Relationship With MYCN Expression

Neuroblastoma (NB) is the most common malignant tumor of infancy. Approximately 60% of NB patients are clinically diagnosed as the stage IV disease and have a very poor prognosis with the ...

Phase I Study of Oral STAT3 Inhibitor, C188-9, in Patients With Advanced Cancers

Many patients have cancers that have increased activity of a protein called STAT3 that contributes critically to the development and growth of their cancer. Despite our knowledge of STAT3'...

Medical and Biotech [MESH] Definitions

A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.

A rho GDP-dissociation inhibitor subtype that is highly expressed in hematopoietic cells and in LYMPHOCYTES. The expression of this subtype is associated with the regulation of CELL PROLIFERATION; TUMORIGENESIS; and APOPTOSIS.

Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.

Intercellular signaling peptides and proteins that regulate the proliferation of new blood vessels under normal physiological conditions (ANGIOGENESIS, PHYSIOLOGICAL). Aberrant expression of angiogenic proteins during disease states such as tumorigenesis can also result in PATHOLOGICAL ANGIOGENESIS.

Chemically-engineered oligonucleotides used to selectively inhibit expression of target genes through sequence-specific binding of corresponding microRNA (miRNA) sites.

Quick Search


DeepDyve research library

Relevant Topics

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Assays
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. ...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Article