Gene/Protein
Disease
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glioblastoma
(
GBM
) is the most aggressive and malignant primary tumor. Angiogenesis plays a critical role in the progression of
GBM
. Previous studies have indicated that long non-coding RNAs (lncRNAs) are abnormally expressed in various cancers and participate in the regulation of the malignant behaviors of tumors. The present study demonstrated that lncRNA antisense 1 to Micro-chromosome maintenance protein 3-associated protein (
MCM3AP
-AS1) was upregulated whereas miR-211 was downregulated in glioma-associated endothelial cells (GECs). Knockdown of
MCM3AP
-AS1 suppressed the cell viability, migration, and tube formation of GECs and played a role in inhibiting angiogenesis of
GBM
in vitro
. Furthermore, knockdown of
MCM3AP
-AS1 increased the expression of miR-211. Luciferase reporter assay implicated that miR-211 targeted KLF5 3'-UTR and consequently inhibited KLF5 expression. Besides, in this study we found that
MCM3AP
-AS1 knockdown decreased KLF5 and AGGF1 expression by upregulating miR-211. In addition, KLF5 was associated with the promoter region of AGGF1. Knockdown of KLF5 decreased AGGF1 expression by transcriptional repression, and also inhibited the activation of PI3K/AKT and ERK1/2 signaling pathways. Overall, this study reveals that
MCM3AP
-AS1/miR-211/KLF5/AGGF1 axis plays a prominent role in the regulation of
GBM
angiogenesis and also serves as new therapeutic target for the anti-angiogenic therapy of glioma.
...
PMID:The Effect of MCM3AP-AS1/miR-211/KLF5/AGGF1 Axis Regulating Glioblastoma Angiogenesis. 2937
Glioblastoma
(
GBM
) has become the most aggressive primary brain tumor in the world. Patients with
GBM
usually have a poor prognosis. The median survival times of
GBM
patients retain less than 2 years. Thus, it is urgent to investigate the molecular mechanism of
GBM
. Recently, studies have demonstrated that transcription factors (TFs) participate in cancer pathology by regulating long noncoding RNAs (lncRNAs). However, the functional and regulatory roles of TF-lncRNA crosstalks are still unclear. In this study, we constructed a global lncRNA-TF network (GLTN) based on competing endogenous RNA. As a result, some topological features of GLTN were identified. A known
GBM
lncRNA
MCM3AP
-AS1 showed multiple central topological features in GLTN. Furthermore, we identified hub genes and extracted the hub-hub pairs from GLTN to form a hub associated lncRNA-TF network (HALTN). Results showed that a risk model combined with multiple hubs had a significant effect on prognosis. Additionally, we performed module searching and two functional modules from HALTN were identified, which were confirmed as risk factors of
GBM
. More importantly, we also identified some core lncRNA-TF crosstalks that might form feedback loops to control the biological processes in
GBM
. Our results demonstrated that the synergistic, competitive lncRNA-TF crosstalks played an important role in pathological processes of
GBM
, and had strong effect on prognosis. All these results can help us to uncover the molecular mechanism and provide a new therapeutic target for
GBM
.
...
PMID:Comprehensive analysis of lncRNA-TF crosstalks and identification of prognostic regulatory feedback loops of glioblastoma using lncRNA/TF-mediated ceRNA network. 3147 23
