Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0028754 (
obesity
)
124,988
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Esophageal adenocarcinoma (EAC) is one of the most common malignancies in the world which is associated the increased prevalence of
obesity
. In the context of
obesity
, leptin can directly contribute to progression of EAC. Adiponectin inhibits leptin-induced oncogenic signaling in EAC cells. However, the exact molecular mechanisms linking
obesity
, adipokines, and EAC remain far from completely understood. In the present study, we tested the role of
ubiquitin-like with PHD and ring finger domains 1
(
UHRF1
) in adiponectin-induced protective effects against leptin-induced EAC cell proliferation. We found that globular adiponectin (gAD) significantly inhibited leptin-induced increase of cell proliferation and decrease of apoptosis in OE 19 cells. Moreover, leptin-induced increase of
UHRF1
expression was suppressed by gAD. Compared with normal controls,
UHRF1
expression was markedly increased in EAC tissues and cell lines. Silence of
UHRF1
increased the expression of cleaved caspase 3 and 9 and Bax, reduced the expression of Bcl-2, promoted apoptosis, and inhibited cell proliferation in OE 19 cells. Overexpression of
UHRF1
significantly blocked gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of adiponectin receptor 1/2 (AdipoR1/2) could inhibit gAD-induced decrease of cell proliferation and increase of apoptosis in leptin-treated cells. Silence of AdipoR2, but not AdipoR1, suppressed gAD-induced decrease of
UHRF1
expression in leptin-treated cells. The results indicated that gAD inhibited the prooncogenic effects of leptin via AdipoR2-mediated suppression of
UHRF1
. Our study provides novel insights into the role of
UHRF1
in the development of EAC and the mechanism of antitumor effect of gAD.
...
PMID:Globular adiponectin inhibits leptin-stimulated esophageal adenocarcinoma cell proliferation via adiponectin receptor 2-mediated suppression of UHRF1. 2828 59
