Enabled homolog (ENAH) regulated by RNA binding protein splicing factor 3b subunit 4 (SF3B4) exacerbates the proliferation, invasion and migration of hepatocellular carcinoma cells via Notch signaling pathway

Deng, Guoming; Luo, Yousong; Zhang, Yaoming; Zhang, Jinfeng; He, Zongyun

doi:10.1080/21655979.2021.2023983

Cited by 9 publications

(5 citation statements)

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“…Hepatocellular carcinoma is a common malignant tumor in the digestive system with high mortality rate and poor prognosis [ 14 ]. Aberrant malignant cellular events including proliferation, migration and invasion may be implicated in the initiation and development of hepatocellular carcinoma [ 15 ]. In this study, both VPS72 and KAT5 were shown to be highly expressed in hepatocellular carcinoma cells, and their high expression was associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Vacuolar protein sorting-associated protein 72 homolog (VPS72) binding to lysine acetyltransferase 5 (KAT5) promotes the proliferation, invasion and migration of hepatocellular carcinoma through regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway

Chen

et al. 2022

Bioengineered

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Hepatocellular carcinoma, a fatal malignancy that occurs in the liver, poses a major public health challenge. This paper attempted to clarify the role and mechanism of vacuolar protein sorting-associated protein 72 homolog (VPS72) in the progression of hepatocellular carcinoma. Firstly, VPS72 expression in hepatocellular carcinoma tissues and the prognostic correlation were analyzed by GEPIA2 database. Western blotting and RT-qPCR assays were used to evaluate VPS72 expression in several hepatocellular carcinoma cell lines. Then, cell proliferation was assessed by cell counting kit-8 and colony formation in HuH-7 cells with VPS72 silencing. Measurement of cell invasion and migration by transwell and wound healing assays. Next, the relationship between VPS72 and lysine acetyltransferase 5 (KAT5) was predicted by bioGRID, STRING and GEIPA2 databases, which was confirmed by Co-immunoprecipitation assay. Subsequently, KAT5 was overexpressed to explore whether VPS72 could regulate the progression of hepatocellular carcinoma by binding to KAT5. And the expression of proteins related to PI3K/AKT signaling was tested with western blotting. Results indicated that VPS72 was highly expressed in hepatocellular carcinoma tissues and cell lines and was associated with poor prognosis. VPS72 knockdown inhibited the proliferation, invasion and migration of HuH-7 cells. In addition, VPS72 could bind to KAT5. KAT5 overexpression reversed the suppressive impacts of VPS72 knockdown on the proliferation, invasion and migration in HuH-7 cells. Besides, VPS72 silencing downregulated p-PI3K and p-AKT expression, which was restored by KAT5 overexpression. Collectively, VPS72 binding to KAT5 promotes the progression of hepatocellular carcinoma through the regulation of PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Vacuolar protein sorting-associated protein 72 homolog (VPS72) binding to lysine acetyltransferase 5 (KAT5) promotes the proliferation, invasion and migration of hepatocellular carcinoma through regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway

Chen

et al. 2022

Bioengineered

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“…Liu et al further demonstrated that SF3B4 drives cell proliferation and metastasis in HCC (57). Deng et al further studied the mechanism and revealed the interaction between SF3B4 and ENAH in HCC, that is, SF3B4-regulated ENAH promotes the development of HCC by activating Notch signaling (58). It has been reported that Guanosine triphosphate binding protein 4 (GTPBP4) is associated with poor prognosis in HCC patients (59).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

et al. 2023

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BackgroundThe development of HCC is often associated with extensive metabolic disturbances. Single cell RNA sequencing (scRNA-seq) provides a better understanding of cellular behavior in the context of complex tumor microenvironments by analyzing individual cell populations. MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data was employed to investigate the metabolic pathways in HCC. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identify six cell subpopulations, namely, T/NK cells, hepatocytes, macrophages, endothelial cells, fibroblasts, and B cells. The gene set enrichment analysis (GSEA) was performed to explore the existence of pathway heterogeneity across different cell subpopulations. Univariate Cox analysis was used to screen genes differentially related to The Overall Survival in TCGA-LIHC patients based on scRNA-seq and bulk RNA-seq datasets, and LASSO analysis was used to select significant predictors for incorporation into multivariate Cox regression. Connectivity Map (CMap) was applied to analysis drug sensitivity of risk models and targeting of potential compounds in high risk groups.ResultsAnalysis of TCGA-LIHC survival data revealed the molecular markers associated with HCC prognosis, including MARCKSL1, SPP1, BSG, CCT3, LAGE3, KPNA2, SF3B4, GTPBP4, PON1, CFHR3, and CYP2C9. The RNA expression of 11 prognosis-related differentially expressed genes (DEGs) in normal human hepatocyte cell line MIHA and HCC cell lines HCC-LM3 and HepG2 were compared by qPCR. Higher KPNA2, LAGE3, SF3B4, CCT3 and GTPBP4 protein expression and lower CYP2C9 and PON1 protein expression in HCC tissues from Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. The results of target compound screening of risk model showed that mercaptopurine is a potential anti-HCC drug.ConclusionThe prognostic genes associated with glucose and lipid metabolic changes in a hepatocyte subpopulation and comparison of liver malignancy cells to normal liver cells may provide insight into the metabolic characteristics of HCC and the potential prognostic biomarkers of tumor-related genes and contribute to developing new treatment strategies for individuals.

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“…Subsequently, a quantitative proteomic analysis was conducted to identify differences in protein abundance in magnum tissues between W40 and W100. As for the top 10 down-regulated differentially expressed proteins in the W100, CMMT6 and EPB41L4B are mainly involved in protein synthesis, secretion and modification process ( Walker et al, 2018 ; Huang et al, 2022 ), RHBDD1, ENAH, MTDH and FBN1 in cell proliferation and migration process ( Yang et al, 2017 ; Xu et al, 2021 ; Deng et al, 2022 ; Shen et al, 2022 ), MGST1 in anti-inflammatory and antioxidant process ( Dai and Lu, 2022 ), BRCA2 in DNA repair process ( Yoshida and Miki, 2004 ), and SMTN in maintaining skeletal framework and muscle protein activity ( Turner and MacDonald, 2014 ). FBN1 and BRCA2 act through the regulation of TGF-β signaling pathway and FA signaling pathway, respectively ( Fang et al, 2020 ; Du et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Histological and molecular difference in albumen quality between post-adolescent hens and aged hens

Chang,

Uchechukwu Edna,

Wang

et al. 2024

Poultry Science

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Enabled homolog (ENAH) regulated by RNA binding protein splicing factor 3b subunit 4 (SF3B4) exacerbates the proliferation, invasion and migration of hepatocellular carcinoma cells via Notch signaling pathway

Cited by 9 publications

References 50 publications

Vacuolar protein sorting-associated protein 72 homolog (VPS72) binding to lysine acetyltransferase 5 (KAT5) promotes the proliferation, invasion and migration of hepatocellular carcinoma through regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway

Vacuolar protein sorting-associated protein 72 homolog (VPS72) binding to lysine acetyltransferase 5 (KAT5) promotes the proliferation, invasion and migration of hepatocellular carcinoma through regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

Histological and molecular difference in albumen quality between post-adolescent hens and aged hens

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