Recruited metastasis suppressor NM23-H2 attenuates expression and activity of peroxisome proliferator-activated receptor δ (PPARδ) in human cholangiocarcinoma.

[cholangiocarcinoma]

Peroxisome proliferator-activated receptor δ (PPAR δ ) is a versatile regulator of distinct biological processes and overexpression of PPAR δ in cancer may be partially related to its suppression of its own co -regulators .To determine whether recruited suppressor proteins bind to and regulate PPAR δ expression , activity and PPAR δ-dependent cholangiocarcinoma proliferation .Yeast two -hybrid assays were done using murine PPAR δ as bait . PPARδ mRNA expression was determined by qPCR . Protein expression was measured by western blot . Immunohistochemistry and fluorescence microscopy were used to determine PPARδ expression and co -localization with NDP Kinase alpha (NM 23 -H 2 ). Cell proliferation assays were performed to determine cell numbers .Yeast two -hybrid screening identified NM 23 -H 2 as a PPARδ binding protein and their interaction was confirmed . Overexpressed PPAR δ or treatment with the agonist GW 501516 resulted in increased cell proliferation . NM 23 -H 2 siRNA activated PPARδ luciferase promoter activity , upregulated PPARδ RNA and protein expression and increased GW 501516 -stimulated CCA growth . Overexpression of NM 23 -H 2 inhibited PPAR δ luciferase promoter activity , downregulated PPAR δ expression and AKT phosphorylation and reduced GW 501516 -stimulated CCA growth .We report the novel association of NM 23 -H 2 with PPAR δ and the negative regulation of PPAR δ expression by NM 23 -H 2 binding to the C-terminal region of PPAR δ . These findings provide evidence that the metastasis suppressor NM 23 -H 2 is involved in the regulation of PPAR δ-mediated proliferation .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated