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Target Concepts:
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Query: UMLS:C0038187 (
starvation
)
24,951
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Histone demethylase
JHDM1D
(also known as KDM7A) modifies the level of methylation in histone and participates in epigenetic gene regulation; however, the role of
JHDM1D
in tumor progression is unknown. Here, we show that
JHDM1D
plays a tumor-suppressive role by regulating angiogenesis. Expression of
JHDM1D
was increased in mouse and human cancer cells under long-term nutrient
starvation
in vitro. Expression of
JHDM1D
mRNA was increased within avascular tumor tissue at the preangiogenic switch, along with increased expression of angiogenesis-regulating genes such as Vegf-A. Stable expression of
JHDM1D
cDNA or siRNA silencing of
JHDM1D
in cancer cells did not affect cell proliferation, anchorage-independent cell growth, or cell cycle progression in vitro. Notably,
JHDM1D
-expressing mouse melanoma (B16) and human cervical carcinoma (HeLa) cells exhibited significantly slower tumor growth in vivo compared with the original cells. This reduction in tumor growth was associated with decreased formation of CD31(+) blood vessels and reduced infiltration of CD11b(+) macrophage linage cells into tumor tissues. Expression of multiple angiogenic factors such as VEGF-B and angiopoietins was decreased in tumor xenografts of
JHDM1D
-expressing B16 and HeLa cells. Our results provide evidence that increased
JHDM1D
expression suppressed tumor growth by down-regulating angiogenesis under nutrient
starvation
.
...
PMID:Increased expression of histone demethylase JHDM1D under nutrient starvation suppresses tumor growth via down-regulating angiogenesis. 2214 93
Long noncoding RNAs play a pivotal role in tumor progression, but their role in cancer cells in the nutrient-starved tumor microenvironment remains unknown. Here, we show that a nutrient
starvation
-responsive long noncoding RNA,
JHDM1D
antisense 1 (JHDM1D-AS1), promotes tumorigenesis by regulating angiogenesis in response to nutrient
starvation
. Expression of
JHDM1D
-AS1 was increased in cancer cells. In addition, expression of
JHDM1D
-AS1 was increased in clinical tumor samples compared to that in normal tissue. Stable expression of
JHDM1D
-AS1 in human pancreatic cancer (PANC-1 and AsPC-1) cells promoted cell growth
in vitro
Remarkably, these
JHDM1D
-AS1-expressing cells showed a significant increase in tumor growth
in vivo
that was associated with increased formation of CD31
+
blood vessels and elevated infiltration of CD11b
+
macrophage lineage cells into tumor tissues. Genome-wide analysis of tumor xenografts revealed that expression of genes for tumor-derived angiogenic factors such as h
HGF
and h
FGF1
concomitant with host-derived inflammation-responsive genes such as m
Mmp3
, m
Mmp9
, m
S100a8
, and m
S100a9
was increased in tumor xenografts of
JHDM1D
-AS1-expressing pancreatic cancer cells, leading to a poor prognosis. Our results provide evidence that increased
JHDM1D
-AS1 expression under nutrient
starvation
accelerates tumor growth by upregulating angiogenesis, thus laying the foundation for improved therapeutic strategies.
...
PMID:Long Noncoding RNA JHDM1D-AS1 Promotes Tumor Growth by Regulating Angiogenesis in Response to Nutrient Starvation. 2865 66
