SUV39H2 promotes colorectal cancer proliferation and metastasis via tri-methylation of the SLIT1 promoter

Shuai, Wendi; Wu, Jiangxue; Chen, Shuai; Liu, Ranyi; Ye, Zhihua; Kuang, Chunmei; Fu, Xiang; Wang, Gaoyuan; Li, Yingchang; Peng, Qi-Hua; Shi, Wei; Li, Yizhuo; Zhou, Qianghua; Huang, Wenlin

doi:10.1016/j.canlet.2018.02.023

Cited by 43 publications

(39 citation statements)

References 74 publications

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“…However, the detailed molecular mechanism is still unclear. Analogously, SUV39H2 was reported to be recruited on the promoter of SLIT1 and promote the proliferation and metastasis of colorectal cancer [ 50 ], suggesting that the epigenetic modulation of SUV39H2 was of importance. Moreover, histone demethylase LSD1 was found to be stabilized by SUV39H2 via methylation [ 45 ], which raised another hypothesis that SUV39H2 correlates with LSD1 during the transcription regulation.…”

Section: Discussionmentioning

confidence: 99%

Identification of SUV39H2 as a potential oncogene in lung adenocarcinoma

Zheng

Wang

et al. 2018

Clin Epigenet

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BackgroundSUV39H2 (suppressor of variegation 3-9 homolog 2), which introduces H3K9me3 to induce transcriptional repression, has been reported to play critical roles in heterochromatin maintenance, DNA repair, and recently, carcinogenesis. Dysregulation of SUV39H2 expression has been observed in several types of cancers. However, neither the genomic landscape nor the clinical significance of SUV39H2 in lung adenocarcinoma has been probed comprehensively.MethodsIn this research, we conducted bioinformatics analysis to primarily sort out potential genes with dysregulated expressions. After we identified SUV39H2, RNA-seq was performed for a high-throughput evaluation of altered gene expression and dysregulated pathways, followed by a series of validations via RT-qPCR and bioinformatics analyses. Finally, to assess the potential oncogenic role of SUV39H2, we employed the invasion assay and clone formation assay in vitro and tumorigenesis assays in mouse models in vivo.ResultsThrough bioinformatics analyses, we found that SUV39H2 underwent a severe upregulation in the tumor tissue, which was also confirmed in the surgically removed tissues. Overexpression of SUV39H2 was mainly associated with its amplification and with shorter patient overall survival. Then, the RNA-seq demonstrated that TPM4, STOM, and OPTN might be affected by the loss of function of SUV39H2. Finally, in vitro and in vivo experiments with SUV39H2 knockdown all suggested a potential role of SUV39H2 in both carcinogenesis and metastasis.ConclusionsSUV39H2 expression was elevated in lung adenocarcinoma. TPM4, OPTN, and STOM were potentially regulated by SUV39H2. SUV39H2 might be a potential oncogene in lung adenocarcinoma, mediating tumorigenesis and metastasis.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0562-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Identification of SUV39H2 as a potential oncogene in lung adenocarcinoma

Zheng

Wang

et al. 2018

Clin Epigenet

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“…Suv39h2 is a histone‐lysine N‐methyltransferase, which is involved primarily in the tri‐methylation of Lysine9 on Histone H3, leading to transcriptional repression (O'Carroll et al, ). While overexpression of Suv39h2 is observed in various cancer types (including colorectal cancer, osteosarcoma, and leukemia) and it is thought to promote tumorigenesis (Carvalho Alves‐Silva et al, ; Piao et al, ; Shuai et al, ), it has no documented role in melanoma, and the expression in melanoma is very low (Rambow et al, ). Importantly, the read‐depth analysis showed that the Suv39h2 gene was present at normal levels (i.e., 2n) in the Tyr::CreER T2‐Lar mice.…”

Section: Discussionmentioning

confidence: 99%

Sequencing two Tyr::CreER^T2 transgenic mouse lines

Aktary

Corvelo

Estrin

et al. 2019

Pigment Cell Melanoma Res

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The Cre/loxP system is a powerful tool that has allowed the study of the effects of specific genes of interest in various biological settings. The Tyr::CreERT2 system allows for the targeted expression and activity of the Cre enzyme in the melanocyte lineage following treatment with tamoxifen, thus providing spatial and temporal control of the expression of specific target genes. Two independent transgenic mouse models, each containing a Tyr::CreERT2 transgene, have been generated and are widely used to study melanocyte transformation. In this study, we performed whole genome sequencing (WGS) on genomic DNA from the two Tyr::CreERT2 mouse models and identified their sites of integration in the C57BL/6 genome. Based on these results, we designed PCR primers to accurately, and efficiently, genotype transgenic mice. Finally, we discussed some of the advantages of each transgenic mouse model.

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“…SUV39H2 catalyzes the H3K9me on the promoter of SLIT guidance ligand 1 (SLIT1) to silence SLIT1 gene. In addition, the expression of KCTD12 and GUCA2A, were also inversely modulated by SUV39H2 [42].…”

Section: Colorectal Carcinomamentioning

confidence: 93%

“…Interacts with AR and MAGE-A11 to enhance AR transcription [41] Ovarian cancer Exon 3 could maintain its stability, localization and catalytic activity [11] Other cancers Bowen's disease Arsenic reprograms E2F1 promoter by deregulating SUV39H2 [71] Although identified as an embryonic-specific protein and restricted to the testis in adult tissues of healthy individuals, SUV39H2 is ubiquitously overexpressed in cancer tissues, such as leukemia, lymphomas, lung cancer, breast cancer, colorectal cancer, gastric cancer, and hepatocellular cancer [1,13,28,30,34,[37][38][39][40][41][42][43][44][45][46][47]. Increasing evidence has confirmed that dysregulation of SUV39H2 contributes to carcinogenesis and is involved in invasion and metastasis of malignancy [33,36,38,41,42,44]. Recently, researches have also clarified that Suv39h2 knockout decrease the incidence of nonalcoholic steatohepatitis and myocardial infarction [48][49][50].…”

Section: Breast Cancermentioning

confidence: 99%

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

Li¹,

Zheng²,

Yang³

2019

J. Cancer

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Epigenetic modifications at the histone level have attracted significant attention because of their roles in tumorigenesis. Suppressor of variegation 3-9 homolog 2 (SUV39H2, also known as KMT1B) is a member of the SUV39 subfamily of lysine methyltransferases (KMTs) that plays a significant role in histone H3-K9 di-/tri-methylation, transcriptional regulation and cell cycle. Overexpressions of SUV39H2 at gene, mRNA and protein levels are known to be associated with a range of cancers: leukemia, lymphomas, lung cancer, breast cancer, colorectal cancer, gastric cancer, hepatocellular cancer and so on. Accumulating evidence indicates that SUV39H2 acts as an oncogene and contributes to the initiation and progression of cancers. It could, therefore, be a promising target for anti-cancer treatment. In this review, we focus on the dysregulation of SUV39H2 in cancers, including its clinical prognostic predictor role, molecular mechanism involved in cancer occurrence and development, relevant inhibitors against cancer, and its epigenetic modification interaction with immunotherapy. A better understanding of the SUV39H2 will be beneficial to the development of molecular-targeted therapies in cancer.

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SUV39H2 promotes colorectal cancer proliferation and metastasis via tri-methylation of the SLIT1 promoter

Cited by 43 publications

References 74 publications

Identification of SUV39H2 as a potential oncogene in lung adenocarcinoma

Identification of SUV39H2 as a potential oncogene in lung adenocarcinoma

Sequencing two Tyr::CreER^T2 transgenic mouse lines

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

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SUV39H2 promotes colorectal cancer proliferation and metastasis via tri-methylation of the SLIT1 promoter

Cited by 43 publications

References 74 publications

Identification of SUV39H2 as a potential oncogene in lung adenocarcinoma

Identification of SUV39H2 as a potential oncogene in lung adenocarcinoma

Sequencing two Tyr::CreERT2 transgenic mouse lines

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

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Sequencing two Tyr::CreER^T2 transgenic mouse lines