Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
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Query: UMLS:C0476089 (
endometrial cancer
)
11,379
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
N
6
-methyladenosine (m
6
A) messenger RNA methylation is a gene regulatory mechanism affecting cell differentiation and proliferation in development and cancer. To study the roles of m
6
A mRNA methylation in cell proliferation and tumorigenicity, we investigated human
endometrial cancer
in which a hotspot R298P mutation is present in a key component of the methyltransferase complex (METTL14). We found that about 70% of endometrial tumours exhibit reductions in m
6
A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3, another component of the methyltransferase complex. These changes lead to increased proliferation and tumorigenicity of
endometrial cancer
cells, likely through activation of the AKT pathway. Reductions in m
6
A methylation lead to decreased expression of the negative AKT regulator
PHLPP2
and increased expression of the positive AKT regulator mTORC2. Together, these results reveal reduced m
6
A mRNA methylation as an oncogenic mechanism in
endometrial cancer
and identify m
6
A methylation as a regulator of AKT signalling.
...
PMID:m
6
A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. 3015 48
The PI3K/AKT pathway is frequently activated in
endometrial carcinoma
. BMI-1 (B-lymphoma Mo-MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI-1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in
endometrial cancer
. The expression of proteins and mRNAs was investigated in
endometrial cancer
specimens and samples of non-neoplastic endometrial tissue by Western blot and RT-PCR, respectively. The impact of BMI-1 down-regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI-1 depletion caused increase in PHLPP1 and
PHLPP2
(PH domain and leucine-rich repeat protein phosphatases 1/2) expression and decrease in phospho-AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI-1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI-1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI-1 and PHLPP1/
PHLPP2
expression was observed in PTEN positive but not PTEN negative cancers. Low
PHLPP2
expression in tumours predicted poorer overall survival. BMI-1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression.
...
PMID:Relationship between polycomb-group protein BMI-1 and phosphatases regulating AKT phosphorylation level in endometrial cancer. 3186 23
