Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.

By Yoshimasa Saito, G. Liang, Gerda Egger, J. Friedman, Jody C. Chuang, Gerhard A. Coetzee, Peter A. Jones. Cancer Cell, 2006

1,364 citations recorded by the source corpus.

Expression profiling of T24 cells revealed that 17 out of 313 human miRNAs were upregulated more than 3-fold by simultaneous treatment with the chromatin-modifying drugs 5-aza-2'-deoxycytidine and 4-phenylbutyric acid. One of these, miR-127, is embedded in a CpG island and is highly induced from its own promoter after treatment. miR-127 is usually expressed as part of a miRNA cluster in normal cells but not in cancer cells, suggesting that it is subject to epigenetic silencing. In addition, the proto-oncogene BCL6, a potential target of miR-127, was translationally downregulated after treatment. These results suggest that DNA demethylation and histone deacetylase inhibition can activate expression of miRNAs that may act as tumor suppressors.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/58e33570b0235a3530d5ea244bc2b015b37ba16a

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Citations in the corpus

Epigenetic Determinants of Cancer. (2016, background): “Yet, others qualify because it is now recognized that promoter CpG island hypermethylation can silence noncoding miRNA genes, which are necessary for modulating signaling networks (Saito and Jones 2006; Saito et al. 2006; Chaffer et al. 2013; Tam and Weinberg 2013; Nickel and Stadler 2014; Sun et al”
Causes and consequences of microRNA dysregulation in cancer (2009, background): “reported that miR-127 is silenced by promoter methylation in bladder tumours and that its expression could be restored by using hypomethylating agents such as azacitidin”
Non-coding RNAs in human disease (2011, background): “These compounds release the epigenetic silencing of tumour suppressor ncRNAs, as has been shown for miRNAs and T-UCRs, thereby stopping tumoural growth and ultimately resulting in the programmed cell death of the transformed cell”
microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer (2011, background): “The mechanisms by which ncRNA expression is altered in cancers are similar to those for protein coding genes, and include epigenetic mechanisms (Lujambio et al., 2007, 2008; Saito et al., 2010).”
MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review (2012, neutral): “…expression in cancer: by treating T24 bladder cancer cells and human ﬁbroblasts with DNMT inhibitor 5-Aza-2 0 -deoxycytidine, Saito and colleagues (Saito et al, 2006) reported a strong upregulation of miR-127, a microRNA characterized by a CpG island promoter able to target the proto-oncogene…”
MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. (2007, background): “Dysregulated miRNA expression may occur via a number of mechanisms, such as gene copy gain or loss (4), germline mutation of precursor miRNA molecules (5), promoter methylation (6), or aberrant miRNA processing due to altered expression of miRNA biogenesis machinery (7).”
Aberrant epigenetic landscape in cancer: how cellular identity goes awry. (2010, background): “Furthermore, this epigenetic repression of mir-127 was associated with changes in histone modifications and may be reversed by adding chromatin-modifying drugs (Saito et al., 2006) in T24 bladder cancer cells.”
microRNAs in cancer (2013, background): “Activation of miR-127, epigenetically repressed in 75% of primary prostate and bladder tumors, inhibits the expression of the proto-oncogene BCL6 (88), suggesting that miR-127 is a tumor suppressor.”
Genomic profiling of microRNA and mRNA reveals deregulated microRNA expression in prostate cancer (2008, background): “Alternatively, microRNA expression could be lost because of mutations or genomic alterations (21) or epigenetic silencing of microRNA loci (27, 28).”
DNA methylation and cancer. (2010, background): “Similarly, DNA hypermethylation of miRNA-127 in bladder cancer results in aberrant expression of the oncogenic factor BCL-6 (Saito et al., 2006).”
MicroRNA (miRNA) in cancer (2015, background): “In bladder cancer cells, a combined treatment with 5-aza-2 ′ -deoxycytidine (5-Aza-CdR) and histone deacetylase (HDAC) inhibitor 4-phenylbutyric acid (PBA) had a significant effect on multiple miRNAs among which miR-127 was most differentially expressed [45].”
A decade of exploring the cancer epigenome — biological and translational implications (2011, background): “This can result in the upregulation of oncogenic targets of the microRNAs, such as BCL-6 (Ref”
miRecords: an integrated resource for microRNA–target interactions (2008, methodology): “The methods commonly applied to over- or misexpress miRNAs include mature miRNA transfection (38), miRNA precursor transfection (39) and indirectly induced miRNA overexpression [using the DNA demethylatingn agent 5-AzaDeoxycytidine (40), or the histone deacetylase inhibitor phenylbutyrate (PBA) (41)”