Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024141 (
systemic lupus erythematosus
)
44,322
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Systemic lupus erythematosus
(
SLE
) damages multiple organs by producing various autoantibodies. In this study, we report that decreased microRNA (miR)-200a-3p causes IL-2 hypoproduction through zinc finger E-box binding homeobox (ZEB)1 and
C-terminal binding protein 2
(
CtBP2
) in a
lupus
-prone mouse. First, we performed RNA sequencing to identify candidate microRNAs and mRNAs involved in the pathogenesis of
SLE
. We found that miR-200a-3p was significantly downregulated, whereas its putative targets, ZEB2 and
CtBP2
, were upregulated in CD4
+
T cells from MRL/lpr-
Tnfrsf6
lpr
mice compared with C57BL/6J mice. ZEB1 and ZEB2 comprise the ZEB family and suppress various genes, including IL-2 by recruiting
CtBP2
. IL-2 plays a critical role in immune tolerance, and insufficient IL-2 production upon stimulation has been recognized in
SLE
pathogenesis. Therefore, we hypothesized that decreased miR-200a-3p causes IL-2 deficit through the ZEB1-
CtBP2
and/or ZEB2-
CtBP2
complex in
SLE
CD4
+
T cells. Overexpression of miR-200a-3p induced IL-2 production by downregulating ZEB1, ZEB2, and
CtBP2
in EL4 cell lines. We further revealed that miR-200a-3p promotes IL-2 expression by reducing the binding of suppressive ZEB1-
CtBP2
and ZEB2-
CtBP2
complexes on negative regulatory element A in the IL-2 promoter in EL4 cells. Interestingly, the ZEB1-
CtBP2
complex on negative regulatory element A was significantly upregulated after PMA/ionomycin stimulation in
lupus
CD4
+
T cells. Our studies have revealed a new epigenetic pathway in the control of IL-2 production in
SLE
whereby low levels of miR-200a-3p accumulate the binding of the ZEB1-
CtBP2
complex to the IL-2 promoter and suppress IL-2 production.
...
PMID:Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells. 2994 62
