Transcriptional down-regulation of IGFBP-3 in human hepatocellular carcinoma cells is mediated by the binding of TIA-1 to its AT-rich element in the 3′-untranslated region

Subramaniam, Kothandharaman; Ooi, London Lucien Peng Jin; Hui, Kam M.

doi:10.1016/j.canlet.2010.05.019

Cited by 20 publications

(19 citation statements)

References 33 publications

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“…The AU-rich element-binding proteins represent one class of RNA-binding proteins that mediate their post-transcriptional function by binding to AU-or U-rich RNA elements (AREs) located primarily within the 3ЈUTRs of target mRNAs. This protein family, which includes the mRNA stability factor human antigen R (HuR) and the translational repressor T-cell intracellular antigen 1 (TIA1), plays a role in the post-transcriptional regulation of a number of biologically important mRNAs (7)(8)(9).…”

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confidence: 99%

Post-transcriptional Regulation of Programmed Cell Death 4 (PDCD4) mRNA by the RNA-binding Proteins Human Antigen R (HuR) and T-cell Intracellular Antigen 1 (TIA1)

Wigington

Jung

Rye

et al. 2015

Journal of Biological Chemistry

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Background: PDCD4 is regulated by multiple mechanisms and is involved in tumor promotion. Results: PDCD4 mRNA is bound by the RNA-binding proteins HuR and TIA1, resulting in modulation of PDCD4 mRNA and protein levels. Conclusion: This study describes a dynamic regulation of PDCD4 mRNA via the 3ЈUTR. Significance: This work reveals an additional regulatory mechanism that modulates levels of the tumor suppressor PDCD4.

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confidence: 99%

Post-transcriptional Regulation of Programmed Cell Death 4 (PDCD4) mRNA by the RNA-binding Proteins Human Antigen R (HuR) and T-cell Intracellular Antigen 1 (TIA1)

Wigington

Jung

Rye

et al. 2015

Journal of Biological Chemistry

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“…As previously described for HCC in adults [17], we also detected a reduced IGFBP3 expression in 6/9 (67%) of pediatric HCC cases (Figure 1D) compared to normal childhood liver tissues. IGFBP3 has recently been described to be transcriptionally downregulated by binding T-cell-restricted intracellular antigen-1 (TIA1), which is also overexpressed in human HCC [20]. Correspondingly, TIA1 is also upregulated in the majority of HB cases (Figure 1E) and is inversely correlated with the expression of IGFBP3 (Figure 1F), although at a low level (rho = -0.3295) Altogether, these data suggest that the downregulation of IGFBP3 might significantly contribute to the activation of the IGF signaling cascade by sustaining the IGF2-induced stimulation in HB.…”

Section: Resultsmentioning

confidence: 99%

“…Degradation of IGFBP3 by cathepsin D, a specific protease of IGFBP3, has been envisaged as an alternative suppression mechanism of IGFBP3, at least at the protein level [17]. Upregulation of the regulatory protein TIA1 that binds to the AU-rich region of the 3'-UTR of IGFBP3 has recently been described to be associated with downregulation of IGFBP3 in primary HCC [20]. As we have detected an inverse correlation of TIA1 and IGFBP3 , it could be assumed that this suppressive mechanism could act in pediatric liver tumors.…”

Section: Discussionmentioning

confidence: 99%

IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors

et al. 2012

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BackgroundHepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of insulin-like growth factor 2 (IGF2), loss of imprinting at the IGF2/H19 locus, and amplification of pleomorphic adenoma gene 1 (PLAG1) are common features in HB, suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this study, we investigated the role of the insulin-like growth factor binding protein 3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers.ResultsThe IGFBP3 gene was highly expressed in normal pediatric livers but was heavily downregulated in four HB cell lines and the majority of HB primary tumors (26/36). Detailed methylation analysis of CpG sites in the IGFBP3 promoter region by bisulfite sequencing revealed a high degree of DNA methylation, which is causatively associated with the suppression of IGFBP3 in HB cell lines. Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted in DNA demethylation and reactivation of the epigenetically silenced IGFBP3 expression. Interestingly, IGFBP3 promoter methylation predominantly occurred in metastatic HB with vascular invasion. Restoring IGFBP3 expression in HB cells resulted in reduced colony formation, migration, and invasion.ConclusionThis study provides the first direct evidence that the reactivation of IGFBP3 decreases aggressive properties of pediatric liver cancer cells and that IGFBP3 promoter methylation might be used as an indicator for vessel-invasive tumor growth in HB patients.

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“…2). [18][19][20][21][22] Some genes, such as Procollagen, type II (COL2A1), 20 Insulin-like growth factor binding protein-3 (IGFBP-3) 23 and Pituitary adenylate cyclase-activating polypeptide (PACAP) 24 could be preferentially regulated by this TIA-dependent pathway.…”

Section: Regulators And/or Modulators Of Gene Expressionmentioning

confidence: 99%

T-cell intracellular antigens in health and disease

Sánchez-Jiménez

Izquierdo

2015

Cell Cycle

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Transcriptional down-regulation of IGFBP-3 in human hepatocellular carcinoma cells is mediated by the binding of TIA-1 to its AT-rich element in the 3′-untranslated region

Cited by 20 publications

References 33 publications

Post-transcriptional Regulation of Programmed Cell Death 4 (PDCD4) mRNA by the RNA-binding Proteins Human Antigen R (HuR) and T-cell Intracellular Antigen 1 (TIA1)

Post-transcriptional Regulation of Programmed Cell Death 4 (PDCD4) mRNA by the RNA-binding Proteins Human Antigen R (HuR) and T-cell Intracellular Antigen 1 (TIA1)

IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors

T-cell intracellular antigens in health and disease

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