Association of MLL3 expression with prognosis in gastric cancer

Li, B; Liu, H Y; Guo, Shaohua; Sun, Peng; Gong, Fang-Ming; Jia, Baoqing

doi:10.4238/2014.september.12.18

Cited by 23 publications

(14 citation statements)

References 9 publications

(8 reference statements)

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“…Moreover, the cellular localization of KMT2C, both nuclear and cytoplasmic, was confirmed by immunofluorescence analysis. The nuclear localization of KMT2C agrees with its function as co-activator of transcriptional factors while the cytoplasmic localization, that was already described for KMT2C [ 20 ], showed that there was an altered intracellular localization of KMT2C (nuclear-cytoplamic trafficking). Recent evidence shows that specific variations of KMT2C can lead to different effects, including the inactivation of the protein or a change in the enzymatic activity [ 21 ].…”

Section: Discussionsupporting

confidence: 77%

The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma

et al. 2018

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Osteosarcoma is the most common paediatric primary non-hematopoietic bone tumor; the survival is related to the response to chemotherapy and development of metastases. KMT2C is a chromatin-modifying and remodelling protein and its expression has never been studied in osteosarcoma. The aim of this study was to understand the role of KMT2C in the osteosarcoma carcinogenesis and metastatic progression to identify a new molecular target and to provide new therapeutic approach.We performed the immunohistochemical and gene expression analysis of KMT2C in 32 samples of patients with diagnosis of osteosarcoma with known clinic-pathological data and we analysed the expression of genes involved in the metastatic pathway in four osteosarcoma cell lines by blocking the KMT2C expression using siRNA.We found a nuclear-cytoplamic trafficking of KMT2C and the cytoplasmic localization was higher than the nuclear localization (p < 0.0001). Moreover, the percentage of cells with cytoplasmic positivity increased from low grade primary tissue to metastatic tissues. The cytoplasmic localization of KMT2C could lead to a change in its function supporting osteosarcoma carcinogenesis and progression. Our hypothesis is that KMT2C could affect the enhancer activity of genes influencing the invasive properties and metastatic potential of osteosarcoma.

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Section: Discussionsupporting

confidence: 77%

The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma

et al. 2018

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“…These results showed that Mll1, Mll3, Ash2l, Wdr5, Rbbp5, Jmjd3, and Utx, are all expressed in insulin positive cells ( Fig 6C ). Interestingly, although Dpy30 staining was predominantly nuclear, all the other proteins showed staining in both the cytoplasm and the nucleus as has been previously determined [ 45 – 48 ]. Together, these data confirm that TrxG proteins are present within β-cells and, given that these complexes can contain both H3K4 histone methyltransferase activity and H3K27me3 demethylase activity, are likely at least partly responsible for the IFNγ, Il-1β, and TNFα mediated conversion of inactive, repressed and bivalent cis-regulatory loci into active loci.…”

Section: Resultssupporting

confidence: 75%

The TrxG Complex Mediates Cytokine Induced De Novo Enhancer Formation in Islets

et al. 2015

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To better understand how β-cells respond to proinflammatory cytokines we mapped the locations of histone 3 lysine 4 monomethylation (H3K4me1), a post-translational histone modification enriched at active and poised cis-regulatory regions, in IFNγ, Il-1β, and TNFα treated pancreatic islets. We identified 96,721 putative cis-regulatory loci, of which 3,590 were generated de novo, 3,204 had increased H3K4me1, and 5,354 had decreased H3K4me1 in IFNγ, Il-1β, and TNFα exposed islets. Roughly 10% of the de novo and increased regions were enriched for the repressive histone modification histone 3 lysine 27 trimethylation (H3K27me3) in untreated cells, and these were frequently associated with chemokine genes. We show that IFNγ, Il-1β, and TNFα exposure overcomes this repression and induces chemokine gene activation in as little as three hours, and that this expression persists for days in absence of continued IFNγ, Il-1β, and TNFα exposure. We implicate trithorax group (TrxG) complexes as likely players in the conversion of these repressed loci to an active state. To block the activity of these complexes, we suppressed Wdr5, a core component of the TrxG complexes, and used the H3K27me3 demethylase inhibitor GSK-J4. We show that GSK-J4 is particularly effective in blunting IFNγ, Il-1β, and TNFα-induced chemokine gene expression in β-cells; however, it induced significant islet-cell apoptosis and β-cell dysfunction. Wdr5 suppression also reduced IFNγ, Il-1β, and TNFα induced chemokine gene expression in β-cells without affecting islet-cell survival or β-cell function after 48hrs, but did begin to increase islet-cell apoptosis and β-cell dysfunction after four days of treatment. Taken together these data suggest that the TrxG complex is potentially a viable target for preventing cytokine induced chemokine gene expression in β-cells.

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“…As we have verified that MLL3 expression level was upregulated in the DCM hearts compared with donor hearts, we hypothesized that the expression levels of Smad3, GATA4 and EGR1 would increase in the hearts of DCM melanoma and pancreatic cancer (37)(38)(39)(40). However, no research has investigated the function of MLL3 on heart diseases currently.…”

Section: Discussionmentioning

confidence: 98%

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

Jiang

Yi²,

et al. 2017

Mol Med

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Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM), while the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families, in DCM are unclear. To this end, 12 normal and 15 DCM heart samples were included in the present study. A murine cardiac remodeling model was induced by transverse aortic constriction (TAC). Real-time polymerase chain reaction was performed to detect the expression levels of MLL families in the mouse and human left ventricles. The mRNA level of MLL3 was significantly increased in the mouse hearts treated with TAC surgery. Compared with normal hearts, higher mRNA and protein level of MLL3 was detected in the DCM hearts, and its expression level was closely associated with left ventricular end diastolic diameter and left ventricular ejection fraction. However, there was no obvious change in the expression levels of other MLL families (MLL, MLL2, MLL4, MLL5, SETD1A and SETD1B) between control and DCM hearts or remodeled mouse hearts. Furthermore, the dimethylated histone H3 lysine 4 (H3K4me2) but not H3K4me3 was significantly increased in the DCM hearts. The protein levels of Smad3, GATA4 and EGR1, which might be regulated by MLL3, were remarkably elevated in the DCM hearts. Our hitherto unrecognized findings indicate that MLL3 has a potential role in the pathological processes of DCM by regulating H3K4me2 and the expression of Smad3, GATA4 and EGR1.

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Association of MLL3 expression with prognosis in gastric cancer

Cited by 23 publications

References 9 publications

The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma

The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma

The TrxG Complex Mediates Cytokine Induced De Novo Enhancer Formation in Islets

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

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