Lefty A is involved in sunitinib resistance of renal cell carcinoma cells via regulation of IL-8
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Ning Cui
, Qiang Han
Abstract
Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. Sunitinib has been used as the standard of treatment for first-line RCC therapy. Understanding mechanisms of sunitinib resistance in RCC cell is important for clinical therapy and drug development. We established sunitinib resistant RCC cells by treating cells with increasing concentrations of sunitinib and named resistant cells as RCC/SR. Lefty A, an important embryonic morphogen, was increased in RCC/SR cells. Targeted inhibition of Lefty via its siRNAs restored the sensitivity of renal resistant cells to sunitinib treatment. It was due to that si-Lefty can decrease the expression of interleukin-8 (IL-8) in RCC/SR cells. Knockdown of IL-8 abolished Lefty-regulated sunitinib sensitivity of RCC cells. Mechanistically, Lefty can regulate IL-8 transcription via activation of p65, one major transcription factor of IL-8. Collectively, our present revealed that Lefty A can regulate sunitinib sensitivity of RCC cells of via NF-κB/IL-8 signals. It indicated that targeted inhibition of Lefty might be a potent approach to overcome sunitinib resistance of RCC.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: None declared.
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Conflict of interest statement: The authors declare no conflict of interest.
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Consent for publication: All authors give the consent for the publish of this study.
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Availability of data and material: All data and material are available.
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© 2021 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- Biophysical applications in structural and molecular biology
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Historic nucleic acids isolated by Friedrich Miescher contain RNA besides DNA
- Protein Structure and Function
- The extracellular region of bovine milk butyrophilin exhibits closer structural similarity to human myelin oligodendrocyte glycoprotein than to immunological BTN family receptors
- Structural insights into the repair mechanism of AGT for methyl-induced DNA damage
- Cell Biology and Signaling
- In vitro osteogenic activities of sulfated derivative of polysaccharide extracted from Tamarindus indica L.
- Synthesis and biological characterization of a new fluorescent probe for vesicular trafficking based on polyazamacrocycle derivative
- Properties of transmembrane helix TM1 of the DcuS sensor kinase of Escherichia coli, the stator for TM2 piston signaling
- Lefty A is involved in sunitinib resistance of renal cell carcinoma cells via regulation of IL-8
- Proteolysis
- Tissue factor pathway inhibitor 2 is a potent kallikrein-related protease 12 inhibitor
Artikel in diesem Heft
- Frontmatter
- Review
- Biophysical applications in structural and molecular biology
- Research Articles/Short Communications
- Genes and Nucleic Acids
- Historic nucleic acids isolated by Friedrich Miescher contain RNA besides DNA
- Protein Structure and Function
- The extracellular region of bovine milk butyrophilin exhibits closer structural similarity to human myelin oligodendrocyte glycoprotein than to immunological BTN family receptors
- Structural insights into the repair mechanism of AGT for methyl-induced DNA damage
- Cell Biology and Signaling
- In vitro osteogenic activities of sulfated derivative of polysaccharide extracted from Tamarindus indica L.
- Synthesis and biological characterization of a new fluorescent probe for vesicular trafficking based on polyazamacrocycle derivative
- Properties of transmembrane helix TM1 of the DcuS sensor kinase of Escherichia coli, the stator for TM2 piston signaling
- Lefty A is involved in sunitinib resistance of renal cell carcinoma cells via regulation of IL-8
- Proteolysis
- Tissue factor pathway inhibitor 2 is a potent kallikrein-related protease 12 inhibitor