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:C1522282 (
EMT
)
2,868
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glioblastoma multiforme (GBM) has been considered the most aggressive glioma type. Temozolomide (TMZ) is the main first-line chemotherapeutic agent for GBM. Decreased
mutS homolog 6
(
MSH6
) expression is clinically recognized as one of the principal reasons for GBM resistance to TMZ. However, the specific functions of
MSH6
in GBM, in addition to its role in mismatch repair, remain unknown.
Methods:
Bioinformatics were employed to analyze
MSH6
mRNA and protein levels in GBM clinical samples and to predict the potential cancer-promoting functions and mechanisms of
MSH6
.
MSH6
levels were silenced or overexpressed in GBM cells to assess its functional effects
in vitro
and
in vivo
. Western blot, qRT-PCR, and immunofluorescence assays were used to explore the relevant molecular mechanisms. Cu
2
(OH)PO
4
@PAA nanoparticles were fabricated through a hydrothermal method. Their MRI and photothermal effects as well as their effect on restraining the
MSH6
-CXCR4-TGFB1 feedback loop were investigated
in vitro
and
in vivo
.
Results:
We demonstrated that
MSH6
is an overexpressed oncogene in human GBM tissues.
MSH6
, CXCR4 and TGFB1 formed a triangular
MSH6
-CXCR4-TGFB1 feedback loop that accelerated gliomagenesis, proliferation (G1 phase), migration and invasion (epithelial-to-mesenchymal transition;
EMT
), stemness, angiogenesis and antiapoptotic effects by regulating the p-STAT3/Slug and p-Smad2/3/ZEB2 signaling pathways in GBM. In addition, the
MSH6
-CXCR4-TGFB1 feedback loop was a vital marker of GBM, making it a promising therapeutic target. Notably, photothermal therapy (PTT) mediated by Cu
2
(OH)PO
4
@PAA + near infrared (NIR) irradiation showed outstanding therapeutic effects, which might be associated with a repressed
MSH6
-CXCR4-TGFB1 feedback loop and its downstream factors in GBM. Simultaneously, the prominent MR imaging (T1WI) ability of Cu
2
(OH)PO
4
@PAA could provide visual guidance for PTT.
Conclusions:
Our findings indicate that the oncogenic
MSH6
-CXCR4-TGFB1 feedback loop is a novel therapeutic target for GBM and that PTT is associated with the inhibition of the
MSH6
-CXCR4-TGFB1 loop.
...
PMID:Oncogenic MSH6-CXCR4-TGFB1 Feedback Loop: A Novel Therapeutic Target of Photothermal Therapy in Glioblastoma Multiforme. 3086 43
