MiR-101 inhibits melanoma cell invasion and proliferation by targeting MITF and EZH2

Luo, Chonglin; Merz, P.; Chen, Yiwei; Dickes, Elke; Pscherer, Armin; Schadendorf, Dirk; Eichmüller, Stefan B.

doi:10.1016/j.canlet.2013.08.021

Cited by 62 publications

(54 citation statements)

References 42 publications

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“…For melanoma, this is best achieved in transgenic mice, in which melanoma is initiated and spontaneously grows in an undisturbed environment without prior ex vivo manipulation of tumour cells 52 . Indeed, the function of EZH2 in selected melanoma cell lines has been controversial and linked to control of proliferation or in vitro migration [28][29][30] . Taking advantage of an inducible and cKO strategy that allows functional gene investigation at different stages of disease in an intact environment, we show that Ezh2 plays a dual role during melanomagenesis.…”

Section: Discussionmentioning

confidence: 99%

“…In human melanoma cells, loss of EZH2 partially interfered with proliferation or invasion capacity, dependent on the cell line and the experimental set up used [28][29][30] . However, a study investigating EZH2 function in a physiological context of melanoma progression, from tumour initiation to metastatic disease, is still missing.…”

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confidence: 99%

“…Our findings demonstrate the requirement of Ezh2 for melanoma initiation. We hypothesized whether this might function through regulation of proliferation, since EZH2 has previously been associated with proliferation of human melanoma cells in vitro [28][29][30] . Interestingly, we observed a heterogeneity with respect to EZH2 expression in melanoma cells of both human biopsies as well as on Tyr::N-Ras Q61K Ink4a À / À skin tumours and metastases, ranging from high EZH2 expression to almost background levels ( Fig.…”

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confidence: 99%

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The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

et al. 2015

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Increased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumorigenesis in vivo remains poor, in particular in metastasizing solid cancers. Here we reveal central roles of EZH2 in promoting growth and metastasis of cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical EZH2 inhibitor GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2 inactivation impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressors connected to increased patient survival. These EZH2 target genes suppress either melanoma growth or metastasis in vivo, revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanoma progression, which makes EZH2 a promising target for novel melanoma therapies.

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Section: Discussionmentioning

confidence: 99%

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The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

et al. 2015

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“…DNA methylation at the promoter region of miR-31 has been shown in a melanoma cell line. 57 It has also been reported that miR-101 58,59 and miR-31 57 both negatively regulate EZH2 and aid cancer progression. These observations provide insight into the functional interactions of mRNA, miRNA, chromatin modifying complexes, and DNA methylation and point to a new era of research in complex regulatory networks in melanoma.…”

Section: Role Of Mirna In Melanomamentioning

confidence: 98%

Epigenetic regulation in human melanoma: past and future

Sarkar

Leung

Baguley³

et al. 2015

Epigenetics

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“…We showed that IL-1b promoted the proliferation and migration of NSCLC cells and that repression of mir-101 represents an important mechanism of its tumor-promoting activity. Recent studies showed that miR-101 is ubiquitously downregulated in many types of cancers and that it represses malignant transformation and cancer progression by negatively regulating a cohort of oncogenes (21)(22)(23)(24)(25)(26)(27). Nevertheless, the potential role of miR-101 in inflammation-promoted tumorigenesis remained largely unclear.…”

Section: Introductionmentioning

confidence: 99%

IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

et al. 2014

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Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the proinflammatory cytokine IL-1b is dramatically elevated in the serum of patients with non-small cell lung cancer (NSCLC). In vitro studies showed that IL-1b promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1b acted through the COX2-HIF1a pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1b upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1b-mediated repression of miR-101 and IL-1b-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1b-miR-101-Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC. Cancer Res; 74(17); 4720-30. Ó2014 AACR.

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MiR-101 inhibits melanoma cell invasion and proliferation by targeting MITF and EZH2

Cited by 62 publications

References 42 publications

The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

Epigenetic regulation in human melanoma: past and future

IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

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