Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma

Jiang, Jun-Jie; Wang, Hui-Ju; Mou, Xiaozhou; Zhang, Huanqing; Chen, YiZhen; Hu, Zhiming

doi:10.1177/15330338211033063

Cited by 6 publications

(3 citation statements)

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“…Lysine acetyltransferase 6B (KAT6B; OMIM 605880) proteins currently constitute the largest and most diverse family across different histone acetyltransferase (HAT) families (Jiang et al, 2021;Shanmugam et al, 2021). Currently, the family includes five human HATs, namely Tip60, MOZ, MORF, HBO1, and MOF, which are known as lysine acetyltransferases (KATs; Lemire et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy

Sun

Luo

Lin

et al. 2023

Molec Gen & Gen Med

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BackgroundLysine acetyltransferase 6B (KAT6B) encodes a highly conserved histone acetyltransferase that regulates the expression of multiple genes and is essential for human growth and development.MethodsWe identified a novel frameshift variant c.3185del (p.leu1062Argfs*52) in a 5‐year‐old Chinese boy and further analyzed KAT6B expression and its interacting complexes and downstream products using real‐time quantitative polymerase chain reaction (qPCR). Furthermore, we assessed its three‐dimensional protein structure and compared the variant with other reported KAT6B variants.ResultsThe deletion changed the leucine at position 1062 into an arginine, resulting in translation termination after base 3340, which may have affected protein stability and protein–protein interactions. KAT6B mRNA expression levels in this case were substantially different from those of the parents and controls in the same age range. There were also significant differences in mRNA expression levels among affected children's parents. RUNX2 and NR5A1, downstream products of the gene, affect the corresponding clinical symptoms. The mRNA expression levels of the two in children were lower than those of their parents and controls in the same age range.ConclusionThis deletion in KAT6B may affect protein function and cause corresponding clinical symptoms through interactions with key complexes and downstream products.

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Section: Introductionmentioning

confidence: 99%

Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy

Sun

Luo

Lin

et al. 2023

Molec Gen & Gen Med

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“…Additionally, KAT6B undergoes genomic loss in small-cell lung cancer, classifying it as a tumor suppressor histone acetyltransferase (61). The expression of KAT6B was found to be significantly lower in hepatocellular carcinoma cells previously (62). Furthermore, there are reports of interactions between KAT6B and ING5, members of the ING family of tumor suppressors (63).…”

Section: Protein Identification and Quantification In The Ags Cells A...mentioning

confidence: 99%

The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells

Eladwy,

Alsherbiny,

Chang

et al. 2024

Front. Nutr.

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A growing body of literature underlines the fundamental role of gut microbiota in the occurrence, treatment, and prognosis of cancer. In particular, the activity of gut microbial metabolites (also known as postbiotics) against different cancer types has been recently reported in several studies. However, their in-depth molecular mechanisms of action and potential interactions with standard chemotherapeutic drugs remain to be fully understood. This research investigates the antiproliferative activities of postbiotics- short-chain fatty acid (SCFA) salts, specifically magnesium acetate (MgA), sodium propionate (NaP), and sodium butyrate (NaB), against the AGS gastric adenocarcinoma cells. Furthermore, the potential synergistic interactions between the most active SCFA salt-NaB and the standard drug dexamethasone (Dex) were explored using the combination index model. The molecular mechanisms of the synergy were investigated using reactive oxygen species (ROS), flow cytometry and biochemometric and liquid chromatography-mass spectrometry (LC–MS)-driven proteomics analyses. NaB exhibited the most significant inhibitory effect (p < 0.05) among the tested SCFA salts against the AGS gastric cancer cells. Additionally, Dex and NaB exhibited strong synergy at a 2:8 ratio (40 μg/mL Dex + 2,400 μg/mL NaB) with significantly greater inhibitory activity (p < 0.05) compared to the mono treatments against the AGS gastric cancer cells. MgA and NaP reduced ROS production, while NaB exhibited pro-oxidative properties. Dex displayed antioxidative effects, and the combination of Dex and NaB (2,8) demonstrated a unique pattern, potentially counteracting the pro-oxidative effects of NaB, highlighting an interaction. Dex and NaB individually and in combination (Dex:NaB 40:2400 μg/mL) induced significant changes in cell populations, suggesting a shift toward apoptosis (p < 0.0001). Analysis of dysregulated proteins in the AGS cells treated with the synergistic combination revealed notable downregulation of the oncogene TNS4, suggesting a potential mechanism for the observed antiproliferative effects. These findings propose the potential implementation of NaB as an adjuvant therapy with Dex. Further investigations into additional combination therapies, in-depth studies of the molecular mechanisms, and in vivo research will provide deeper insights into the use of these postbiotics in cancer, particularly in gastric malignancies.

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“…Similarly, lower KAT6B expression was also observed in hepatocellular carcinoma (HCC) as compared to the normal liver tissue which was directly related to gender, AFP (Alpha Fetoprotein) level and tumour size. [281]. KAT6B positively regulates prostate cancer cell growth via PI3K/AKT signalling [282].…”

Section: Involvement Of Novel Fbxw7 Targets In Various Pathomechanismsmentioning

confidence: 99%

MAPK dependent regulation of FBXW7 phosphodegrons

Singh

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Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma

Cited by 6 publications

References 32 publications

Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy

Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy

The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells

MAPK dependent regulation of FBXW7 phosphodegrons

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