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)
Bromodomain-containing protein 9
(
BRD9
) has a critical role in human squamous cell lung cancer, acute myeloid leukemia, and malignant rhabdoid tumors. However, the expression and biological role of
BRD9
in
hepatocellular carcinoma
(
HCC
) is poorly understood. In this study,
BRD9
expression was found to be elevated in
HCC
through data mining of public databases. Next, we confirmed that the expression of
BRD9
was increased in
HCC
tissues compared with that in adjacent non-tumor tissues. The upregulated level of
BRD9
was also observed in
HCC
cells in comparison to LO2 cells. The increased
BRD9
expression was correlated with unfavorable clinicopathological features. A high level of
BRD9
predicted a poorer overall survival and disease-free survival of
HCC
patients. Functionally,
BRD9
overexpression facilitated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of Hep3B cells. Conversely, either
BRD9
depletion or pharmacological inhibition of
BRD9
resulted in the reduced proliferation and invasiveness of HCCLM3 cells. In addition, the
BRD9
knockdown restrained the growth and metastasis of HCCLM3 cells in vivo. Mechanistically,
BRD9
positively regulated TUFT1 expression and AKT activation in
HCC
cells. ChIP-qPCR analysis indicated that
BRD9
promoted the binding of P300 acetyltransferase to the TUFT1 promoter and epigenetically regulated TUFT1 expression by increasing H3K27Ac in the promoter. Notably, either TUFT1 knockdown or AKT inhibitor (MK2206) abrogated the promoting effects of
BRD9
on the proliferation, migration, invasion, and EMT of Hep3B cells. The forced expression of TUFT1 abolished the effects of
BRD9
knockdown on the growth and metastasis of HCCLM3 cells. Altogether, these data indicate that
BRD9
promotes the growth and metastasis of
HCC
cells by activating the TUFT1/AKT pathway and may serve as a promising biomarker and therapeutic target for
HCC
.
...
PMID:Bromodomain-containing protein 9 promotes the growth and metastasis of human hepatocellular carcinoma by activating the TUFT1/AKT pathway. 3290 35
