miR-449a targets HDAC-1 and induces growth arrest in prostate cancer

Noonan, Emily J.; Place, Robert F.; Pookot, Deepa; Basak, Shashwati; Whitson, Jared M.; Hirata, Hiroshi; Giardina, Charles; Dahiya, Rajvir

doi:10.1038/onc.2009.19

Cited by 361 publications

(291 citation statements)

References 58 publications

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“…Altogether, these results suggest that some miRNAs may be under direct beta-catenin/TCF4 control with others being regulated by downstream effectors and/or depend on simultaneous inputs from additional factors (Labbe et al, 2007). dnTCF4-responsive miRNAs are downregulated in CRC specimens and CRC cell lines Among the numerous miRNAs altered as a consequence of dnTCF4 overexpression, we noticed several of the upregulated miRNAs to have been previously associated with restriction of cancer cell growth (miR449a, (Henson et al, 2009;Noonan et al, 2009;Slaby et al, 2009;Chen et al, 2010;Ding et al, 2010;Ostenfeld et al, 2010). Interestingly, in addition to prominent growth-inhibitory miRNAs commonly downregulated in CRC, such as miR-126 and miR-145 (Guo et al, 2008;Schepeler et al, 2008), several miRNAs with unknown function in CRC cells (for example, miR-574-3p, miR-30e-3p and miR-139-5p) were also upregulated, which prompted us to hypothesize that some of these miRNAs may also be dysregulated in CRC.…”

Section: Resultsmentioning

confidence: 78%

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

et al. 2011

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Section: Resultsmentioning

confidence: 78%

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

et al. 2011

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“…Hence, we tested whether miR-449 may act in parallel to miR-34 in growth suppression and apoptosis, as suggested by its activity in prostate cancer cells. 30 First, we transfected plasmids encoding each miRNA into HCT116 cells with or without p53, followed by antibiotic selection of stable transfectants. Both miR-34a and miR-449a/b suppressed clonogenic survival in this system, in a partially p53-independent fashion (Figure 4a and b).…”

Section: Resultsmentioning

confidence: 99%

E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis

2009

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E2F1 is a positive regulator of cell cycle progression and also a potent inducer of apoptosis, especially when activated by DNA damage. We identified E2F1-inducible microRNAs (miRNAs) by microarray hybridization and found that the levels of miRNAs 449a and 449b, as well as their host gene CDC20B, are strongly upregulated by E2F1. High miR-449 levels were found in testes, lung, and trachea, but not in testicular and other cancer cells. MiR-449a/b structurally resemble the p53-inducible miRNA 34 family. In agreement with a putative tumor-suppressive role, miR-449a as well as miR-34a reduced proliferation and strongly promoted apoptosis by at least partially p53-independent mechanisms. Both miRNAs reduced the levels of CDK6, implying miR-449 in a negative feedback mechanism for E2F1. Moreover, miR-449a and miR-34a diminished the deacetylase Sirt1 and augmented p53 acetylation. We propose that both miRNAs provide a twofold safety mechanism to avoid excessive E2F1-induced proliferation by cell cycle arrest and by apoptosis. While responding to different transactivators, miRNAs 449 and 34 each repress E2F1, but promote p53 activity, allowing efficient cross-talk between two major DNA damage-responsive gene regulators.

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“…miR-29 promotes osteogenesis by targeting HDAC4 (H Li et al, 2009), and miR-2861 controls osteoblast differentiation by repressing HDAC5 (Z. . The cartilagespecific miR-140 regulates HDAC4 (Tuddenham et al, 2006), and MiR-449a targets HDAC1 in prostate cancer (Noonan et al, 2009). However, the action of microRNA on epigenetic markers can be indirect.…”

Section: Micrornas and Inflammationmentioning

confidence: 99%

Epigenetic Mechanisms in Inflammation

2010

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Epigenetic modifications occur in response to environmental changes and play a fundamental role in gene expression following environmental stimuli. Major epigenetic events include methylation and acetylation of histones and regulatory factors, DNA methylation, and small non-coding RNAs. Diet, pollution, infections, and other environmental factors have profound effects on epigenetic modifications and trigger susceptibility to diseases. Despite a growing body of literature addressing the role of the environment on gene expression, very little is known about the epigenetic pathways involved in the modulation of inflammatory and anti-inflammatory genes. This review summarizes the current knowledge about epigenetic control mechanisms during the inflammatory response.

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miR-449a targets HDAC-1 and induces growth arrest in prostate cancer

Cited by 361 publications

References 58 publications

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis

Epigenetic Mechanisms in Inflammation

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