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MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.

Sionov RV - ISRN Hematol (2013)

Bottom Line: There is still a need to develop clinical tests that can predict the outcome of GC therapy.In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts.The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.

View Article: PubMed Central - PubMed

Affiliation: The Department of Biochemistry and Molecular Biology, The Institute for Medical Research-Israel-Canada, Hadassah Medical School, The Hebrew University of Jerusalem, Ein-Kerem, 91120 Jerusalem, Israel.

ABSTRACT
The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.

No MeSH data available.


Related in: MedlinePlus

Regulation of Bim expression. Details are described in Sections 2.2.3–2.2.5.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig1: Regulation of Bim expression. Details are described in Sections 2.2.3–2.2.5.

Mentions: Bim expression is tightly regulated both at the transcription and posttranscriptional levels [215, 218] (Figure 1). No GRE element has been found in the Bim promoter. Rather, GC-induced Bim expression in lymphoid cells requires p38 activation and is mediated by the forkhead transcription factor FoxO3a/FKHR-L1 [226]. FoxO3a has also been shown to promote Bim transcription in various other cellular systems [227–229] and may cooperate with Runx1 (Runt-related transcription factor 1) [230]. Differential recruitment of FoxO3a to the Bim promoter was observed after dexamethasone treatment of GC-sensitive versus GC-resistant childhood ALL xenografts [29]. FoxO3 was found to be an immediate early GR target, whose transcription is further enhanced by stimuli that activate the AMP-activated protein kinase AMPK [231]. The activity of FoxO transcription factors is tightly regulated, inhibited by Akt and ERK signaling, while promoted by p38 signaling [232–236].


MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.

Sionov RV - ISRN Hematol (2013)

Regulation of Bim expression. Details are described in Sections 2.2.3–2.2.5.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569899&req=5

fig1: Regulation of Bim expression. Details are described in Sections 2.2.3–2.2.5.
Mentions: Bim expression is tightly regulated both at the transcription and posttranscriptional levels [215, 218] (Figure 1). No GRE element has been found in the Bim promoter. Rather, GC-induced Bim expression in lymphoid cells requires p38 activation and is mediated by the forkhead transcription factor FoxO3a/FKHR-L1 [226]. FoxO3a has also been shown to promote Bim transcription in various other cellular systems [227–229] and may cooperate with Runx1 (Runt-related transcription factor 1) [230]. Differential recruitment of FoxO3a to the Bim promoter was observed after dexamethasone treatment of GC-sensitive versus GC-resistant childhood ALL xenografts [29]. FoxO3 was found to be an immediate early GR target, whose transcription is further enhanced by stimuli that activate the AMP-activated protein kinase AMPK [231]. The activity of FoxO transcription factors is tightly regulated, inhibited by Akt and ERK signaling, while promoted by p38 signaling [232–236].

Bottom Line: There is still a need to develop clinical tests that can predict the outcome of GC therapy.In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts.The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.

View Article: PubMed Central - PubMed

Affiliation: The Department of Biochemistry and Molecular Biology, The Institute for Medical Research-Israel-Canada, Hadassah Medical School, The Hebrew University of Jerusalem, Ein-Kerem, 91120 Jerusalem, Israel.

ABSTRACT
The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.

No MeSH data available.


Related in: MedlinePlus