Down‐regulation of the expression of RB18A/MED1, a cofactor of transcription, triggers strong tumorigenic phenotype of human melanoma cells

Ndong, Jean De La Croix; Jean, Didier; Rousselet, Nathalie; Frade, Raymond

doi:10.1002/ijc.24253

Cited by 25 publications

(30 citation statements)

References 41 publications

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“…Med1 has equivocal functions in different tumors. It functions as a tumor-suppressor gene and inhibits invasion and metastasis in lung carcinomas (27) and melanoma cells (28). Conversely, deficiency of Med1 protects hepatocytes from chemical carcinogen-induced hepatocarcinogenesis (29), and loss of Med1 significantly decreased proliferation of prostate cancer cells (30).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31

et al. 2014

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MicroRNA-1 (miR-1) has been shown to function as a critical gene regulator in multiple types of cancers. However, the role of miR-1 in osteosarcoma has not been totally clarified. In the present study, we investigated the effects of miR-1 on osteosarcoma and the underlying mechanism. We found that miR-1 was downregulated in osteosarcoma tissues and osteosarcoma cell lines. Restoration of miR-1 significantly suppressed osteosarcoma cell proliferation by inhibiting cell cycle progression. Mediator complex subunit 1 (Med1) and 31 (Med31) were validated as targets of miR-1 in osteosarcoma by luciferase reporter assay. Downregulation of Med1 and Med31 suppressed the proliferation of osteosarcoma cells, and overexpression of Med1 and Med31 abrogated the effects of miR-1 on cell proliferation. Furthermore, both miR-1 and knockdown of Med1 or Med31 reduced the expression of met proto-oncogene (MET) and blocked the downstream signaling of MET responding to hepatocyte growth factor (HGF). Taken together, the findings of this study suggest that Med1 and Med31 serve as potential gene therapeutic targets in osteosarcoma and miR-1 may prove to be a promising agent.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31

et al. 2014

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“…Both protein complexes have already been shown to regulate melanoma development. The deletion of MED1, a component of the mediator complex, is known to increase melanoma aggressiveness (38). In the same way, when underexpressed in a cell line exhibiting a BRAF mutation (V600E) as in 501mel cells, SMARCB1, a component of the SMARC complex, prevents senescence and promotes melanomagenesis (39,40).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Hypoxia-inducible Factor 2α Nuclear Interactome in Melanoma Cells Reveals Master Proteins Involved in Melanoma Development

Steunou

Ducoux-Petit

Lazar

et al. 2013

Molecular & Cellular Proteomics

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Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors that play a key role in cellular adaptation to hypoxia. HIF proteins are composed of an ␣ subunit regulated by oxygen pressure (essentially HIF1␣ or HIF2␣) and a constitutively expressed ␤ subunit. These proteins are often overexpressed in cancer cells, and HIF overexpression frequently correlates with poor prognosis, making HIF proteins promising therapeutic targets. HIF proteins are involved in melanoma initiation and progression; however, the specific function of HIF2 in melanoma has not yet been studied comprehensively. Identifying protein complexes is a valuable way to uncover protein function, and affinity purification coupled with mass spectrometry and label-free quantification is a reliable method for this approach. We therefore applied quantitative interaction proteomics to identify exhaustively the nuclear complexes containing HIF2␣ in a human melanoma cell line, 501mel. We report, for the first time, a high-throughput analysis of the interactome of an HIF subunit. Seventy proteins were identified that interact with HIF2␣, including some well-known HIF partners and some new interactors. The new HIF2␣ partners microphthalmia-associated transcription factor, SOX10, and AP2␣, which are master actors of melanoma development, were confirmed via coimmunoprecipitation experiments. Their ability to bind to HIF1␣ was also tested: microphthalmia-associated transcription factor and SOX10 were confirmed as HIF1␣ partners, but the transcription factor AP2␣ was not. AP2␣ expression correlates with low invasive capacities. Interestingly, we demonstrated that when HIF2␣ was overexpressed, only cells expressing large amounts of AP2␣ exhibited decreased invasive capacities in hypoxia relative to normoxia. Hypoxia-inducible transcription factors (HIFs)1 are central mediators of cellular adaptation to hypoxia that control the expression of genes involved in anaerobic metabolism, intracellular pH, angiogenesis, and cell growth and survival (1). HIF proteins are heterodimers consisting of an oxygen-regulated ␣ subunit and a constitutively expressed ␤ subunit (also referred to as the arylhydrocarbon receptor nuclear translocator, or ARNT). Three isoforms have been described for each subunit; most HIF function, however, has been attributed to HIF1␣, HIF2␣, and HIF1␤ (2). HIF1␣ is detected in almost all tissues, whereas HIF2␣ (also known as EPAS1, for endothelial PAS protein 1) is restricted to certain tissues. HIF2 is expressed notably in hypoxic endothelium but also in distinct cell populations in the brain, liver, kidney, lung, and intestine (3). HIF␣ proteins are regulated post-translationally as a function of the partial pressure of oxygen. In normoxic conditions, the protein is rapidly hydroxylated by prolyl hydroxylases and then recognized by the von Hippel-Lindau protein, a component of an E3-ubiquitin ligase complex that targets the ␣ subunit for degradation by the proteasome. When the partial pressure of oxygen is low, prolyl hydroxylase activi...

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“…The TRAP220 expression was elevated in half of the human prostate cancer tissues and TRAP220 plays a coregulatory role in the cell proliferation and survival of prostate cancer [24]. However, recent study revealed that TRAP220 knockdown in human melanoma cells in vitro increased the invasive properties and TRAP220 knockdown in melanoma cells in vivo switched the melanoma phenotype from non-tumorigenic to strongly tumorigenic in nude mice [25]. Furthermore, Gade et al showed that TRAP220-expressing A549 human lung adenocarcinoma cells formed significantly fewer metastases compared with the controls and a majority of primary lung cancer tissues showed a consistent loss of the TRAP220 and tumor metastasis suppressor DAPK1 expressions; this suggests that TRAP220 loss contributes to the attenuation of antitumor responses and the promotion of tumor growth [26].…”

Section: Covariatementioning

confidence: 96%

A different TRAP220 expression in distinct histologic subtypes of lung adenocarcinoma and the prognostic significance

Yun

Son

et al. 2011

Lung Cancer

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Down‐regulation of the expression of RB18A/MED1, a cofactor of transcription, triggers strong tumorigenic phenotype of human melanoma cells

Cited by 25 publications

References 41 publications

MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31

MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31

Identification of the Hypoxia-inducible Factor 2α Nuclear Interactome in Melanoma Cells Reveals Master Proteins Involved in Melanoma Development

A different TRAP220 expression in distinct histologic subtypes of lung adenocarcinoma and the prognostic significance

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