miR-502 medaited histone methyltransferase SET8 expression is associated with outcome of esophageal squamous cell carcinoma

Wang, Cuiju; Wu, Jianhua; Zhao, Yue; Guo, Zhanjun

doi:10.1038/srep32921

Cited by 28 publications

(19 citation statements)

References 36 publications

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“…In addition, SET8 knockdown inhibited migration and invasion of HCC cells. These results are in line with previous studies that highlighted the role of SET8 in progression and metastasis of a variety of tumours, such as papillary thyroid cancer, oesophageal squamous www.nature.com/scientificreports www.nature.com/scientificreports/ cell carcinoma and renal cell carcinoma [26][27][28] . Consistent with these data, SET8 overexpression and UNC0379 treatment also proved that SET8 is an oncogene that favours HCC development.…”

Section: Discussionsupporting

confidence: 92%

Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma

Qiao

et al. 2020

Sci Rep

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The expression of lysine methyltransferase SET8, which is involved in carcinogenesis of many types of human cancers through monomethylation of histone H4 lysine 20 (H4K20), is associated with the prognosis of hepatocellular carcinoma (HCC). We performed a functional analysis for SET8 to assess its effect on HCC progression. SET8 knockdown inhibited proliferation, migration and invasion of HCC cells. SET8 knockdown also inhibited tumour growth in a human xenograft mouse model. Overexpression of SET8 displayed the reverse effect, while treatment with the SET8 inhibitor UNC0379 produced an effect similar to SET8 knockdown. In addition, drug sensitivity testing in SET8-siRNA transfected HCC cells indicated that docetaxel inhibited cell growth dramatically, as demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Furthermore, gene expression microarray analysis showed that genes altered after SET8 knockdown were clustered in pathways related to tumorigenesis and metastasis. Our data suggests that targeting SET8 for HCC therapy can inhibit the proliferation and invasion of HCC cells as well as increase their sensitivity to chemotherapy.

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Section: Discussionsupporting

confidence: 92%

Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma

Qiao

et al. 2020

Sci Rep

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“…SET8 was reported to be associated with the development of several tumors ( 23 , 30 , 31 ). So, we next examined whether SET8 -knockdown affects renal carcinoma 786-O cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

miR‑502‑mediated histone methyltransferase SET8 expression is associated with clear cell renal cell carcinoma risk

Zhang

Guo

et al. 2017

Oncol Lett

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Genetic variants may affect the interactions between microRNAs (miRNAs/miRs) and their target genes by modulating their binding affinity or by creating, or destroying a miRNA-binding site. SET domain containing (lysine methyltransferase) 8 (SET8) is the sole lysine methyltransferase that catalyzes the monomethylation of histone H4 lysine 20, and is associated with tumor growth, invasion and metastasis. In the present study, the rs16917496 polymorphism within the miR-502 binding site of the SET8 mRNA 3′ untranslated region (3′UTR) in patients with clear cell renal cell carcinoma (ccRCC) and healthy controls was genotyped. The SET8 CC genotype was associated with a decreased ccRCC risk compared with the CT [P=0.003; odds ratio (OR)=0.318; 95% confidence interval (CI), 0.146–0.691], TT (P=0.011; OR=0.402; 95% CI, 0.197–0.819) and CT+TT (P=0.004; OR=0.370; 95% CI, 0.186–0.736) genotypes. The SET8 CC genotype was associated with reduced SET8 expression based on immunostaining of ccRCC tissue. Low SET8 protein levels were negatively associated with tumor-node-metastasis staging in patients with ccRCC according to the size of tumor and lymph node metastases. SET8-knockdown inhibited renal carcinoma 786-O cell proliferation, migration and invasion. c-Myc and matrix metalloproteinase-7 mRNA expression were downregulated upon SET8-knockdown in renal carcinoma 786-O cells. These data indicated that SET8 may be a functional tumor promoter and that its activation, which is partially regulated by changing the miR-502 and SET8 3′UTR binding affinity, may serve an important role in ccRCC development.

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“…For example, in hepatocellular carcinoma (HCC), non-small cell lung carcinoma (NSCLC), bladder cancer, chronic myelogenous leukemia, and NHL 13 , 16 , 17 , SET8 functions largely as an oncogene. In esophageal cancers, SET8 mediated by miR-502 modifies the outcome by inhibiting proliferation and invasion and by promoting the apoptosis of tumor cells 18 . In breast cancer, SET8 is involved in EMT 15 .…”

Section: Discussionmentioning

confidence: 99%

Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells

et al. 2020

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Gastric cancer (GC) is the most common cancer throughout the world. Despite advances of the treatments, detailed oncogenic mechanisms are largely unknown. In our previous study, we investigated microRNA (miR) expression profiles in human GC using miR microarrays. We found miR-192/215 were upregulated in GC tissues. Then gene microarray was implemented to discover the targets of miR-192/215. We compared the expression profile of BGC823 cells transfected with miR-192/215 inhibitors, and HFE145 cells transfected with miR-192/-215 mimics, respectively. SET8 was identified as a proposed target based on the expression change of more than twofold. SET8 belongs to the SET domain-containing methyltransferase family and specifically catalyzes monomethylation of H4K20me. It is involved in diverse functions in tumorigenesis and metastasis. Therefore, we focused on the contributions of miR-192/215/SET8 axis to the development of GC. In this study, we observe that functionally, SET8 regulated by miR-192/215 is involved in GC-related biological activities. SET8 is also found to trigger oncogene-induced senescence (OIS) in GC in vivo and in vitro, which is dependent on the DDR (DNA damage response) and p53. Our findings reveal that SET8 functions as a negative regulator of metastasis via the OIS-signaling pathway. Taken together, we investigated the functional significance, molecular mechanisms, and clinical impact of miR-192/215/SET8/p53 in GC.

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miR-502 medaited histone methyltransferase SET8 expression is associated with outcome of esophageal squamous cell carcinoma

Cited by 28 publications

References 36 publications

Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma

Downregulation of histone methyltransferase SET8 inhibits progression of hepatocellular carcinoma

miR‑502‑mediated histone methyltransferase SET8 expression is associated with clear cell renal cell carcinoma risk

Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells

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