RNA-interference-mediated downregulation of Pin1 suppresses tumorigenicity of malignant melanoma A375 cells.
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.
Department of Pharmacology, Chinese Academy of Medical Sciences, Beijing, China.
J
J
Jin
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Y
Zhang
Y
Y
Li
H
H
Zhang
H
H
Li
X
X
Yuan
X
X
Li
W
W
Zhou
B
B
Xu
C
C
Zhang
Z
Z
Zhang
L
L
Zhu
X
X
Chen
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003114:Colony-Forming Units Assay; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction
D035683:MicroRNAs; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse