HuR/Methyl-HuR and AUF1 Regulate the MAT Expressed During Liver Proliferation, Differentiation, and Carcinogenesis

Vázquez–Chantada, Mercedes; Fernández‐Ramos, David; Embade, Nieves; Martínez–López, Nuria; Varela‐Rey, Marta; Woodhoo, Ashwin; Luka, Zigmund; Wagner, Conrad; Anglim, Paul P.; Finnell, Richard H.; Caballería, Juan; Laird-Offringa, Ite A.; Gorospe, Myriam; Lu, Shelly C.; Mato, José M.; Martínez‐Chantar, M. Luz

doi:10.1053/j.gastro.2010.01.032

Cited by 115 publications

(155 citation statements)

References 35 publications

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“…HCC specimens express higher AUF1 protein levels, and knockdown of AUF1 increased MAT1A mRNA level (23). However, these mechanisms are difficult to target, since they can affect numerous other genes.…”

Section: Figurementioning

confidence: 99%

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MicroRNAs regulate methionine adenosyltransferase 1A expression in hepatocellular carcinoma

et al. 2012

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Section: Figurementioning

confidence: 99%

“…showed that the MAT1A 3′ UTR binds to the AU-rich RNA binding factor 1 (AUF1), which is one of the hnRNP proteins known to destabilize target mRNAs (23). HCC specimens express higher AUF1 protein levels, and knockdown of AUF1 increased MAT1A mRNA level (23).…”

Section: Figurementioning

confidence: 99%

MicroRNAs regulate methionine adenosyltransferase 1A expression in hepatocellular carcinoma

et al. 2012

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“…15). Slides were then incubated with primary anti-HuR antibody (EMD Millipore) followed by biotinylated secondary antibody.…”

Section: Ihcmentioning

confidence: 99%

HuR Suppresses Fas Expression and Correlates with Patient Outcome in Liver Cancer

Zhu

Berkova

Mathur

et al. 2015

Molecular Cancer Research

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Hepatocellular carcinomas (HCC) show resistance to chemotherapy and have blunt response to apoptotic stimuli. HCC cell lines express low levels of the Fas death receptor and are resistant to FasL stimulation, whereas immortalized hepatocytes are sensitive. The variable Fas transcript levels and consistently low Fas protein in HCC cells suggest posttranscriptional regulation of Fas expression. The 3 0 -untranslated region (UTR) of Fas mRNA was found to interact with the ribonucleoprotein Human Antigen R (HuR) to block mRNA translation. Silencing of HuR in HCC cells increased the levels of cell surface Fas and sensitized HCC cells to FasL. Two AU-rich domains within the 3 0 -UTR of Fas mRNA were identified as putative HuR-binding sites and were found to mediate the translational regulation in reporter assay. Hydrodynamic transfection of HuR plasmid into mice induced downregulation of Fas expression in livers and established functional resistance to the killing effects of Fas agonist. Human HCC tumor tissues showed significantly higher overall and cytoplasmic HuR staining compared with normal liver tissues, and the high HuR staining score correlated with worse survival of patients with early-stage HCC. Combined, the protumorigenic ribonucleoprotein HuR blocks the translation of Fas mRNA and effectively prevents Fas-mediated apoptosis in HCC, suggesting that targeting HuR would sensitize cells to apoptotic stimuli and reverse tumorigenic properties.Implications: Demonstrating how death receptor signaling pathways are altered during progression of HCC will enable the development of better methods to restore this potent apoptosis mechanism. Mol Cancer Res; 13(5); 809-18. Ó2015 AACR.

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“…HuR can exist in methylated or un-methylated form. While, the presence of methylated HuR protein is associated with destabilization of MAT2A mRNA and decreased expression of α2 subunit of MAT II isoform, the un-methylated HuR exerts an opposite effect (Vázquez-Chantada et al 2010).…”

Section: Effect Of Altered Expression Of Mat Genes On Carcinogenesismentioning

confidence: 99%

Role of S-adenosylmethionine cycle in carcinogenesis

Murín¹,

Vidomanová²,

Kowtharapu³

et al. 2017

gpb

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Abstract. Alterations in enzymatic activities underlying the cellular capacity to maintain functional S-adenosylmethionine (SAM) cycle are associated with modified levels of its constituents. Since SAM is the most prominent donor of methyl group for sustaining the methylation pattern of macromolecules by methyltransferases, its availability is an essential prerequisite for sustaining the methylation pattern of nucleic acids and proteins. In addition, increased intracellular concentrations of S-adenosylhomocysteine and homocysteine, another two constituents of SAM cycle, exerts an inhibitory effect on the enzymatic activity of methyltranferases. While methylation pattern of DNA and histones is considered as an important regulatory hallmark in epigenetically regulated gene expression, amended methylation of several cellular proteins, including transcription factors, affects their activity and stability. Indeed, varied DNA methylome is a common consequence of disturbed SAM cycle and is linked with molecular changes underlying the transformation of the cells that may underlay the carcinogenesis. Here we summarize the recent evidences about the impact of disturbed SAM cycle on carcinogenesis.

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HuR/Methyl-HuR and AUF1 Regulate the MAT Expressed During Liver Proliferation, Differentiation, and Carcinogenesis

Cited by 115 publications

References 35 publications

MicroRNAs regulate methionine adenosyltransferase 1A expression in hepatocellular carcinoma

MicroRNAs regulate methionine adenosyltransferase 1A expression in hepatocellular carcinoma

HuR Suppresses Fas Expression and Correlates with Patient Outcome in Liver Cancer

Role of S-adenosylmethionine cycle in carcinogenesis

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