Loss of MGA mediated Polycomb repression promotes tumor progression and invasiveness

Mathsyaraja, Haritha; Catchpole, Jonathen; Eastwood, Emily; Babaeva, Ekaterina; Geuenich, Michael; Cheng, Pei Feng; Freie, Brian; Ayers, Jessica; Yu, Ming; Wu, Nan; Poudel, Kumud R.; Koehne, Amanda; Grady, William M.; Houghton, A. McGarry; Shiio, Yuzuru; MacPherson, David; Eisenman, Robert N.

doi:10.1101/2020.10.16.334714

Cited by 4 publications

(4 citation statements)

References 71 publications

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“…Its structure allows the regulation of both MAX-network and T-domain target genes, either as an activator or repressor [ 6 , 7 , 8 ]. Inactivation of MGA is frequent in human cancer, and a recent study has demonstrated that MGA functions as a tumor suppressor in murine models of lung carcinoma and in colorectal cancer organoids, partly due to the de-repression of MYC target genes [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Multiple Faces of MNT and Its Role as a MYC Modulator

Liaño-Pons

Arsenian-Henriksson

León

2021

Cancers

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MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.

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Section: Introductionmentioning

confidence: 99%

The Multiple Faces of MNT and Its Role as a MYC Modulator

Liaño-Pons

Arsenian-Henriksson

León

2021

Cancers

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“…The next probe cg07713411 is near gene MGA. MGA has been widely reported to be associated with tumor invasion ( 43 ) and progression ( 44 ). MGA has also been reported to contribute to MYC-mediated pathway in colorectal cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

Identifying anal and cervical tumorigenesis-associated methylation signaling with machine learning methods

et al. 2022

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Cervical and anal carcinoma are neoplastic diseases with various intraepithelial neoplasia stages. The underlying mechanisms for cancer initiation and progression have not been fully revealed. DNA methylation has been shown to be aberrantly regulated during tumorigenesis in anal and cervical carcinoma, revealing the important roles of DNA methylation signaling as a biomarker to distinguish cancer stages in clinics. In this research, several machine learning methods were used to analyze the methylation profiles on anal and cervical carcinoma samples, which were divided into three classes representing various stages of tumor progression. Advanced feature selection methods, including Boruta, LASSO, LightGBM, and MCFS, were used to select methylation features that are highly correlated with cancer progression. Some methylation probes including cg01550828 and its corresponding gene RNF168 have been reported to be associated with human papilloma virus-related anal cancer. As for biomarkers for cervical carcinoma, cg27012396 and its functional gene HDAC4 were confirmed to regulate the glycolysis and survival of hypoxic tumor cells in cervical carcinoma. Furthermore, we developed effective classifiers for identifying various tumor stages and derived classification rules that reflect the quantitative impact of methylation on tumorigenesis. The current study identified methylation signals associated with the development of cervical and anal carcinoma at qualitative and quantitative levels using advanced machine learning methods.

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“…SNV analysis gives similar results with literature for example EGFR and KRAS mutations are mutually exclusive in LUAD samples that is confirmed again [ 9 ]. Additionally, EGFR [ 102 ], MGA [ 103 ], SMARCA4 [ 104 ], ATM [ 105 ], RBM10 [ 106 ] and KDM5C [ 107 ] which are lung cancer related genes are mutated only in LUAD but not in LUSC. On the other hand, CDKN2A [ 108 ], PTEN [ 109 ] and HRAS [ 110 ] genes are mutated only in LUSC.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

Zengin

Önal-Süzek

2021

JPM

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Lung cancer is the second most frequently diagnosed cancer type and responsible for the highest number of cancer deaths worldwide. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are subtypes of non-small-cell lung cancer which has the highest frequency of lung cancer cases. We aimed to analyze genomic and transcriptomic variations including simple nucleotide variations (SNVs), copy number variations (CNVs) and differential expressed genes (DEGs) in order to find key genes and pathways for diagnostic and prognostic prediction for lung adenocarcinoma and lung squamous cell carcinoma. We performed a univariate Cox model and then lasso-regularized Cox model with leave-one-out cross-validation using The Cancer Genome Atlas (TCGA) gene expression data in tumor samples. We generated 35- and 33-gene signatures for prognostic risk prediction based on the overall survival time of the patients with LUAD and LUSC, respectively. When we clustered patients into high- and low-risk groups, the survival analysis showed highly significant results with high prediction power for both training and test datasets. Then, we characterized the differences including significant SNVs, CNVs, DEGs, active subnetworks, and the pathways. We described the results for the risk groups and cancer subtypes separately to identify specific genomic alterations between both high-risk groups and cancer subtypes. Both LUAD and LUSC high-risk groups have more downregulated immune pathways and upregulated metabolic pathways. On the other hand, low-risk groups have both up- and downregulated genes on cancer-related pathways. Both LUAD and LUSC have important gene alterations such as CDKN2A and CDKN2B deletions with different frequencies. SOX2 amplification occurs in LUSC and PSMD4 amplification in LUAD. EGFR and KRAS mutations are mutually exclusive in LUAD samples. EGFR, MGA, SMARCA4, ATM, RBM10, and KDM5C genes are mutated only in LUAD but not in LUSC. CDKN2A, PTEN, and HRAS genes are mutated only in LUSC samples. The low-risk groups of both LUAD and LUSC tend to have a higher number of SNVs, CNVs, and DEGs. The signature genes and altered genes have the potential to be used as diagnostic and prognostic biomarkers for personalized oncology.

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Loss of MGA mediated Polycomb repression promotes tumor progression and invasiveness

Cited by 4 publications

References 71 publications

The Multiple Faces of MNT and Its Role as a MYC Modulator

The Multiple Faces of MNT and Its Role as a MYC Modulator

Identifying anal and cervical tumorigenesis-associated methylation signaling with machine learning methods

Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

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