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:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
N
6
-Methyladenosine (m
6
A) is a prevalent modification present in the mRNAs of higher eukaryotes.
YTH domain family 2
(
YTHDF2
), an m
6
A "reader" protein, can recognize mRNA m
6
A sites to mediate mRNA degradation. However, the regulatory mechanism of
YTHDF2
is poorly understood. To this end, we investigated the post-transcriptional regulation of
YTHDF2
. Bioinformatics analysis suggested that the microRNA miR-145 might target the 3'-untranslated region (3'-UTR) of
YTHDF2
mRNA. The levels of miR-145 were negatively correlated with those of
YTHDF2
mRNA in clinical
hepatocellular carcinoma
(
HCC
) tissues, and immunohistochemical staining revealed that
YTHDF2
was closely associated with malignancy of
HCC
. Interestingly, miR-145 decreased the luciferase activities of 3'-UTR of
YTHDF2
mRNA. Mutation of predicted miR-145 binding sites in the 3'-UTR of
YTHDF2
mRNA abolished the miR-145-induced decrease in luciferase activity. Overexpression of miR-145 dose-dependently down-regulated
YTHDF2
expression in
HCC
cells at the levels of both mRNA and protein. Conversely, inhibition of miR-145 resulted in the up-regulation of
YTHDF2
in the cells. Dot blot analysis and immunofluorescence staining revealed that the overexpression of miR-145 strongly increased m
6
A levels relative to those in control
HCC
cells, and this increase could be blocked by
YTHDF2
overexpression. Moreover, miR-145 inhibition strongly decreased m
6
A levels, which were rescued by treatment with a small interfering RNA-based
YTHDF2
knockdown. Thus, we conclude that miR-145 modulates m
6
A levels by targeting the 3'-UTR of
YTHDF2
mRNA in
HCC
cells.
...
PMID:MicroRNA-145 Modulates
N
6
-Methyladenosine Levels by Targeting the 3'-Untranslated mRNA Region of the
N
6
-Methyladenosine Binding YTH Domain Family 2 Protein. 2810 5
