SMYD3: a regulator of epigenetic and signaling pathways in cancer

Bernard, Benjamin; Nigam, Nupur; Burkitt, Kyunghee; Saloura, Vassiliki

doi:10.1186/s13148-021-01021-9

Cited by 49 publications

(39 citation statements)

References 83 publications

(115 reference statements)

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“…SMYD3 promotes tumour cell migration and invasion by strengthening epithelial-mesenchymal cells and enhancing telomerase activity during the cell cycle [ 44 – 47 ]. Furthermore, SMYD3 expression is a key risk factor for esophageal [ 47 ], breast [ 46 ], bladder [ 48 ], and other [ 49 ] cancers. A recent study indicated that AP2M1 was overexpressed in adenoid cystic and mucoepidermoid carcinomas and could serve as a prognostic marker of hepatocellular carcinoma [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Mast cell marker gene signature in head and neck squamous cell carcinoma

et al. 2022

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Background Mast cells can reshape the tumour immune microenvironment and greatly affect tumour occurrence and development. However, mast cell gene prognostic and predictive value in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study was conducted to identify and establish a prognostic mast cell gene signature (MCS) for assessing the prognosis and immunotherapy response of patients with HNSCC. Methods Mast cell marker genes in HNSCC were identified using single-cell RNA sequencing analysis. A dataset from The Cancer Genome Atlas was divided into a training cohort to construct the MCS model and a testing cohort to validate the model. Fluorescence in-situ hybridisation was used to evaluate the MCS model gene expression in tissue sections from patients with HNSCC who had been treated with programmed cell death-1 inhibitors and further validate the MCS. Results A prognostic MCS comprising nine genes (KIT, RAB32, CATSPER1, SMYD3, LINC00996, SOCS1, AP2M1, LAT, and HSP90B1) was generated by comprehensively analysing clinical features and 47 mast cell-related genes. The MCS effectively distinguished survival outcomes across the training, testing, and entire cohorts as an independent prognostic factor. Furthermore, we identified patients with favourable immune cell infiltration status and immunotherapy responses. Fluorescence in-situ hybridisation supported the MCS immunotherapy response of patients with HNSCC prediction, showing increased high-risk gene expression and reduced low-risk gene expression in immunotherapy-insensitive patients. Conclusions Our MCS provides insight into the roles of mast cells in HNSCC prognosis and may have applications as an immunotherapy response predictive indicator in patients with HNSCC and a reference for immunotherapy decision-making.

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Section: Discussionmentioning

confidence: 99%

Mast cell marker gene signature in head and neck squamous cell carcinoma

et al. 2022

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“…SMYD3 is a lysine HMT that functions as a transcriptional potentiator of genes by multiple possible mechanisms including binding to specific DNA sequences (5’-CCCTCC-3’ or 5’-GGAGGG-3’), interacting with transcription factors and trimethylated H3K4 (the fourth lysine of histone 3) tails and so on [ 12 ]. Upregulation of SMYD3 has been identified in several types of cancer, such as breast and colorectal cancer, and is associated with tumor proliferation and metastasis [ 13 , 14 ]. These findings imply that SMYD3 might play a crucial role in tumor progression.…”

Section: Introductionmentioning

confidence: 99%

SMYD3 promotes aerobic glycolysis in diffuse large B-cell lymphoma via H3K4me3-mediated PKM2 transcription

Tian

Shi

et al. 2022

Cell Death Dis

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Genetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.

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“…In the surrogate intrinsic breast cancer subtypes (e.g., luminal A, luminal B, basal, and HER2 + ; TCGA, 2012) and in other TNBC subtypes, high ANKHD1 expression was significantly associated with or showed a tendency to associate with better RFS (Supporting Information: Figure 5). Among the best‐characterized interactors of ANKHD1 regarding clinical impact (Andrade et al, 2017; Bernard et al, 2021; Calses et al, 2019; Zhou et al, 2019), SMYD3 (Supporting Information: Figure 6), but not YAP1 (Supporting Information: Figure 7), had a similar profile to ANKHD1 in the clinical outcome of patients with breast cancer.…”

Section: Resultsmentioning

confidence: 94%

“…Survival curves were estimated using the Kaplan-Meier method, and the hazard ratio (HR), 95% confidence interval, and p values are indicated in the graphs. best-characterized interactors of ANKHD1 regarding clinical impact (Andrade et al, 2017;Bernard et al, 2021;Calses et al, 2019;Zhou et al, 2019), SMYD3 (Supporting Information: Figure 6), but not YAP1 (Supporting Information: Figure 7), had a similar profile to ANKHD1 in the clinical outcome of patients with breast cancer.…”

Section: Ankhd1 Mrna Expression Correlates With Breast Cancer Patient...mentioning

confidence: 96%

ANKHD1 contributes to the malignant phenotype of triple‐negative breast cancer cells

Almeida

Costa-Lotufo

et al. 2022

Cell Biology International

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Ankyrin repeat and KH domain-containing protein 1, ANKHD1, has been identified as a regulator of signaling pathways and cellular processes of relevance in carcinogenesis. However, the role of ANKHD1 in breast cancer remains unclear.The aim of the present study was to characterize the expression pattern and involvement of ANKHD1 in the malignant phenotype of breast cancer cell lines and to investigate the clinical relevance of ANKHD1 in a breast cancer context. Gene and protein expressions were assessed in the cell lines by quantitative reverse transcription PCR and Western blot analysis, respectively, and ANKHD1 silencing through siRNA transfection was conducted for further in vitro functional assays. The expression of ANKHD1 was identified in non-tumorigenic breast epithelium and breast cancer cell lines, but differences in cellular localization were found among the neoplasia subtypes. ANKHD1 silencing reduced the viability, clonogenicity, and migration of triple-negative breast cancer (TNBC) cells. Bioinformatics analyses demonstrated that patients with triple-negative basal-like 2 and mesenchymal breast cancer subtypes had high ANKHD1 expression associated with poor recurrence-free survival. Therefore, these data indicate that ANKHD1 relevance in breast cancer varies among its subtypes, indicating the importance of ANKHD1 in TNBC.

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SMYD3: a regulator of epigenetic and signaling pathways in cancer

Cited by 49 publications

References 83 publications

Mast cell marker gene signature in head and neck squamous cell carcinoma

Mast cell marker gene signature in head and neck squamous cell carcinoma

SMYD3 promotes aerobic glycolysis in diffuse large B-cell lymphoma via H3K4me3-mediated PKM2 transcription

ANKHD1 contributes to the malignant phenotype of triple‐negative breast cancer cells

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