Cell Death Dis:BRD9 activates the TUFT1/AKT path pathfectal path to promote the growth and metastasis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the sixth most common malignant tumor, is the third most common cause of cancer-related deaths, with approximately 780,000 newly confirmed cases and 750,000 deaths each year.
pathogenesis of liver cancer is a complex process, including persistent inflammatory damage and fibrosis deposition.
Although significant progress has been made in imaging diagnosis, surgery, chemotherapy and targeted therapy in recent years, HCC's five-year survival rate is still less than 20% due to rapid tumor growth, recurrence and high metastasis rates.
, a better understanding of the molecular mechanisms of the development of liver cancer is conducive to the development of new targeted drugs and the improvement of the overall prognosis of the disease.
previous studies have shown that BRD9 (Bromodomain-containing protein 9) plays a crucial role in human squamous cell lung cancer, acute myeloid leukemia, and malignant transverse fibroids.
the level of expression and biological function of BRD9 in HCC has yet to be studied.
the study, through public database analysis, found that the expression level of BRD9 in liver cancer increased.
researchers further validated that BRD9 was more expressed in liver cancer tissue than in neighboring non-cancerous tissues.
increase in BND9 expression levels was also observed in HCC cells compared to LO2 cells.
increased BRD9 is associated with poor clinical pathological characteristics in patients.
high expression level of BRD9 corresponds to the lower overall survival rate and disease-free survival rate of HCC patients.
study has shown that over-expression of BRD9 promotes the proliferation, migration, invasion and endocystic-interstrate transformation (EMT) of Hep3B cells.
, knocking out BRD9 or pharmacological inhibition of its expression can lead to a decrease in HCCLM3 cell proliferation and invasion.
addition, knocking down BRD9 inhibits the growth and metastasis of HCCLM3 cells.
mechanism studies have shown that BRD9 regulates the expression of TUFT1 and the activation of AKT in HCC cells.
ChIP-qPCR results show that BRD9 regulates the expression of TUFT1 at the surface genetic level by promoting the binding of P300 acetyl transferase with the TUFT1 promoter region, which improves the level of H3K27Ac modification in the promoter region.
it is worth noting that knocking down TUFT1 or giving AKT inhibitors (MK2206) all blocked the promotion of BRD9 to Hep3B cell proliferation, migration, invasion and EMT.
and forced expression of TUFT1 can eliminate the effect of the above knock-down BRD9 on HCCLM3 cell growth and metastasis.
all, the study showed that BRD9 can promote the growth and metastasis of liver cancer cells by activating the TUFT1/AKT pathrapy, which may be a potential biomarker and therapeutic target for HCC.
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