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: EC:2.7.12.2 (
MEK
)
18,161
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Homeodomain-containing gene C10 (
HOXC10
), known to regulate cell differentiation and proliferation, is a key negative regulator in the browning of white adipose tissue in mice. Sheep is an important farm animal that provides meat for human consumption, with fat content being an important meat quality determinant; however, there is no report about the role of
HOXC10
in sheep adipocytes or adipogenesis. In this study, we investigated the effect of
HOXC10
on proliferation and adipogenic differentiation in sheep bone marrow mesenchymal stem cells (sBMSCs). In sBMSCs,
HOXC10
overexpression promoted cell proliferation and upregulated the expression of p-PI3K, p-AKT, p-p70S6K, p-
MEK
, and p-ERK, whereas
HOXC10
knockdown was associated with the opposite effects. These results suggested that
HOXC10
may promote cell proliferation by activating the
MEK
/ERK and PI3K/AKT/mTOR/p70S6K signaling pathways. In addition, we found that
HOXC10
expression was negatively associated with lipid accumulation in adipogenic-differentiated sBMSCs.
HOXC10
overexpression in sBMSCs significantly decreased lipid droplet accumulation and suppressed the expression of adipogenic-specific genes, including ACC, LPL, PPARG, and FABP4, while
HOXC10
knockdown was associated with the opposite effects. Furthermore, our study suggested a new regulatory mechanism of the effect of
HOXC10
on lipid accumulation and metabolism;
HOXC10
may negatively regulate lipid accumulation in adipogenic-differentiated sBMSCs, at least in part, by suppressing LPL expression. Overall, our research not only contributes to a better understanding of the mechanism of lipid accumulation and metabolism in sheep, but also shed light on meat quality control in the future.
...
PMID:HOXC10 promotes proliferation and attenuates lipid accumulation of sheep bone marrow mesenchymal stem cells. 3181 13
While KRAS mutations are common in non-small cell lung cancer (NSCLC), effective treatments are lacking. Here, we report that half of KRAS-mutant NSCLCs aberrantly express the homeobox protein
HOXC10
, largely due to unappreciated defects in PRC2, which confers sensitivity to combined BET/
MEK
inhibitors in xenograft and PDX models. Efficacy of the combination is dependent on suppression of
HOXC10
by BET inhibitors. We further show that
HOXC10
regulates the expression of pre-replication complex (pre-RC) proteins in sensitive tumors. Accordingly, BET/
MEK
inhibitors suppress pre-RC proteins in cycling cells, triggering stalled replication, DNA damage, and death. These studies reveal a promising therapeutic strategy for KRAS-mutant NSCLCs, identify a predictive biomarker of response, and define a subset of NSCLCs with a targetable epigenetic vulnerability.
...
PMID:A Deregulated HOX Gene Axis Confers an Epigenetic Vulnerability in KRAS-Mutant Lung Cancers. 3224 38
