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Published on: July 20, 2019
RNA-interference-mediated downregulation of Pin1 suppresses tumorigenicity of malignant melanoma A375 cells
1Department of Pharmacology, Chinese Academy of Medical Sciences, Beijing, China.
Abstract:
The peptidyl-prolyl isomerase Pin1 is overexpressed in many human cancers, including melanoma. To investigate its possible role in oncogenesis of melanoma and as a therapeutic target, we suppressed Pin1 expression in the human melanoma cell line A375 by microRNA (miRNA) interference technology. Two stable clones with suppressed Pin1 were established by stable transfection of miRNA plasmid targeting Pin1 into A375 cells. Both clones showed reduced proliferation and invasion in vitro and suppressed tumorigenic potential in athymic mice. Furthermore, Pin1 inhibition also resulted in decreased phosphorylation of Akt and repressed expression of C-Jun N-terminal kinase and pro-matrix metalloproteinase 2, which were associated closely with the development of melanoma. These findings indicate that Pin1 plays an important role in the tumorigenesis of melanoma and might serve as a promising therapeutic target.
Insights
Peptidyl-prolyl isomerase Pin1 (Pin1) overexpression drives melanoma. Suppressing Pin1 in melanoma cells reduced proliferation, invasion, and tumor growth, indicating Pin1 is a potential therapeutic target for melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Peptidyl-prolyl isomerase Pin1 (Pin1) is frequently overexpressed in human cancers, including melanoma.
- Pin1's role in melanoma oncogenesis and its potential as a therapeutic target require further investigation.
Purpose of the Study:
- To investigate the role of Pin1 in melanoma development and progression.
- To evaluate Pin1 as a potential therapeutic target for melanoma treatment.
Main Methods:
- Pin1 expression was suppressed in the human melanoma cell line A375 using microRNA (miRNA) interference technology.
- Stable clones with suppressed Pin1 were generated via miRNA plasmid transfection.
- Proliferation, invasion, and tumorigenic potential in athymic mice were assessed.
Main Results:
- Melanoma cell clones with suppressed Pin1 exhibited reduced proliferation and invasion in vitro.
- Tumorigenic potential was suppressed in athymic mice.
- Pin1 inhibition led to decreased Akt phosphorylation and repressed expression of c-Jun N-terminal kinase and pro-matrix metalloproteinase 2.
Conclusions:
- Pin1 plays a significant role in melanoma tumorigenesis.
- Pin1 inhibition demonstrates therapeutic potential for melanoma treatment.
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