Expression of SET domain bifurcated histone lysine methyltransferase 1 and its clinical prognostic significance in hepatocellular carcinoma

Wang, Chunnian; Li, Zheng; Ye, Fusang; Ji, Shengqiang; Lu, Changjiang; Zhang, Huizhi

doi:10.1002/jcla.24090

Cited by 3 publications

(2 citation statements)

References 15 publications

(24 reference statements)

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“…It is demonstrated that SETDB1 is an oncogene and an important prognostic factor in some tumors. SETDB1 expression is upregulated in LIHC tissues and is associated with tumor size, enhanced stage, and TNM classification [ 52 ]. Similarly, for TCGA-LIHC patients, we observed that the expression level of SETDB1 is significantly elevated in tumor tissues compared to that in paracancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

Pancancer Analyses Reveal Genomics and Clinical Characteristics of the SETDB1 in Human Tumors

Lin

Xiao

Chen

et al. 2022

Journal of Oncology

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Background. Malignant tumor is one of the most common diseases that seriously affect human health. The prior literature has reported the biological function and potential therapeutic targets of SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) as an oncogene. However, SETDB1 has rarely been analyzed from a pan-cancer perspective. Methods. Bioinformatics analysis tools and databases, including GeneCards, National Center for Biotechnology Information (NCBI), UniProt, Illustrator for Biological Sequences (IBS), Human Protein Atlas (HPA), GEPIA, TIMER2, Sangerbox 3.0, UALCAN, Kaplan-Meier (K-M) plotter, cBioPortal, Catalogue Of Somatic Mutations In Cancer (COSMIC), PhosphoSitePlus, TISIDB, STRING, and GeneMANIA, were utilized to clarify the biological functions and clinical significance of SETDB1 from a pan-cancer perspective. Results. In this study, the pan-cancer analysis demonstrated that SETDB1 showed significantly differential expression in most tumor tissues and paracancerous tissues, and SETDB1 expression was associated with clinicopathological features and clinical prognosis. We also found that SETDB1 mutations occurred in most tumors and were related to tumorigenesis. In addition, DNA methylation of SETDB1 primarily occurred at the cg10444928 site and was associated with prognosis in several human tumors. The predicted phosphorylation site of SETDB1 was Ser1006. We found that SETDB1 was significantly related to the specific tumor-infiltrating immune cell populations and expression of clinically targetable immune checkpoints and may be a promising immunotherapy target. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses also indicated that SETDB1 may function as crucial regulator in carcinogenesis of human cancers. Conclusions. SETDB1 is an important oncogene involved in tumorigenesis and tumor progression through different biological mechanisms. Furthermore, SETDB1 may be a potential therapeutic target for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Pancancer Analyses Reveal Genomics and Clinical Characteristics of the SETDB1 in Human Tumors

Lin

Xiao

Chen

et al. 2022

Journal of Oncology

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“…SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is an epigenetic modifier primarily involved in H3K9 methylation but can also mediate the methylation of H3K27 and DNA (6). Previous studies have implicated aberrant SETDB1 expression in the development of various types of cancer, including head and neck, lung, breast, ovarian, colorectal and hepatocellular cancer and leukemia (7)(8)(9)(10)(11)(12)(13). One of the primary mechanisms through which SETDB1 affects cancer prognosis is the promotion of cell proliferation via AKT methylation at lysine residues 64, 140 and 142, which results in Thr-308 phosphorylation and increases AKT activity (14,15).…”

Section: Introductionmentioning

confidence: 99%

SETDB1 induces lenalidomide resistance in multiple myeloma cells via epithelial‑mesenchymal transition and PI3K/AKT pathway activation

et al. 2023

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SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is a histone H3K9 methyltransferase that stimulates cell proliferation by methylating AKT, which contributes to drug resistance in multiple myeloma (MM). Lenalidomide is an immunomodulatory agent widely used in the treatment of MM. However, lenalidomide resistance occurs in patients with MM. Currently, the role of SETDB1 in lenalidomide resistance in MM remains unclear. Thus, the present study aimed to explore the functional association between SETDB1 and lenalidomide resistance in MM. The analysis of GEO datasets revealed that SETDB1 was upregulated in lenalidomide-resistant MM cells and that its expression was associated with poor prognosis of patients with MM. Apoptosis analysis revealed that overexpression of SETDB1 in MM cells significantly decreased apoptosis, while knockdown of SETDB1 increased apoptosis. Furthermore, the IC 50 value of lenalidomide in MM cells increased following SETDB1 overexpression and decreased following SETDB1 silencing. Additionally, SETDB1 mediated epithelial-mesenchymal transition (EMT) and activated the PI3K/AKT pathway. Mechanistic analysis revealed that inhibition of PI3K/AKT signaling in MM cells increased apoptosis, sensitized the cells to lenalidomide and inhibited EMT, whereas SETDB1 overexpression inhibited the effects of PI3K/AKT cascade inhibition. In conclusion, the findings of the present study indicated that SETDB1 promoted lenalidomide resistance in MM cells by promoting EMT and the PI3K/AKT signaling pathway. Thus, SETDB1 may be a potential therapeutic target for MM.

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Expression of SET domain bifurcated histone lysine methyltransferase 1 and its clinical prognostic significance in hepatocellular carcinoma

Wang¹,

Li²,

Ye³

et al. 2021

Clinical Laboratory Analysis

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Background To detect the expression of histone methyltransferase SETDB1 in hepatocellular carcinoma, and to analyze the relationship between SETDB1 expression and tumor size, microvascular invasion, pTNM stage, gender, age, tumor number, tumor differentiation, and other clinicopathological characteristics. Methods Immunohistochemical method was used to detect the expression of SETDB1 proteins in liver cancer tissues and adjacent tissues of 100 cases. The qRT‐PCR method was used to detect the expression of SETDB1 mRNA in hepatocellular carcinoma and adjacent tissues of 64 cases. Results The expression of SETDB1 protein and mRNA in hepatocellular carcinoma was higher than that of adjacent normal liver tissue (p < 0.05). High protein expression of SETDB1 was associated with tumor size, MVI presence, and pTNM stage (p < 0.05). Univariate analysis revealed that the tumor size, tumor differentiation, MVI grade, and pTNM stage were correlated with DFS, while tumor size, MVI grade, pTNM stage, and SETDB1 protein expression were correlated with OS. Multivariate analysis showed that the combination of MVI grade and pTNM stage has statistical significance in predicting prognosis, while SETDB1 protein expression was not significant prognosis factor. Conclusions SETDB1 has a certain role in HCC progression and may act as a prognostic predictor concerning the survival of HCC patients.

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Expression of SET domain bifurcated histone lysine methyltransferase 1 and its clinical prognostic significance in hepatocellular carcinoma

Cited by 3 publications

References 15 publications

Pancancer Analyses Reveal Genomics and Clinical Characteristics of the SETDB1 in Human Tumors

Pancancer Analyses Reveal Genomics and Clinical Characteristics of the SETDB1 in Human Tumors

SETDB1 induces lenalidomide resistance in multiple myeloma cells via epithelial‑mesenchymal transition and PI3K/AKT pathway activation

Expression of SET domain bifurcated histone lysine methyltransferase 1 and its clinical prognostic significance in hepatocellular carcinoma

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