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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

The complexity of GC-induced apoptosis. A summary of the main issue discussed in this paper.
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Related In: Results  -  Collection


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fig6: The complexity of GC-induced apoptosis. A summary of the main issue discussed in this paper.

Mentions: From all we have learned above, any microRNA that modulates any of the many factors regulating GC-induced apoptosis may affect the apoptotic response to GCs (Figures 1–6). These include microRNAs that affect GR expression (e.g., miR-18, miR-124a, miR-130b, miR-142, and miR-181a), those affecting Bim expression (miR-26a, miR-93, miR-17~92, miR-106a~363, and miR-106b~25) or its transcription factor FoxO3 (e.g., miR-1, miR-21, miR-27a, miR-96, miR-135b, miR-155, and miR-182), those affecting PTEN expression (miR-17~92, miR-106b~25, miR-21, miR-26a, miR-29b, miR-214, miR-216a, miR-217, miR-221, and miR-222) or mTOR (e.g., miR-101), and those downregulating directly or indirectly the anti-apoptotic proteins Bcl-2, Bcl-XL, Mcl-1, XIAP, and CYLD (e.g., miR-15a~16, miR-181a/b, miR-34a, miR-125b, miR-29a/b/c, miR-101, miR-133b, miR-193b, miR-512, let-7, and miR-491). The effect of some of these microRNAs on GC-sensitivity has already been described above and will not be repeated here. Rather, I will present here some data from primary samples showing the influence of microRNAs on clinical outcome.


MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.

Sionov RV - ISRN Hematol (2013)

The complexity of GC-induced apoptosis. A summary of the main issue discussed in this paper.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: The complexity of GC-induced apoptosis. A summary of the main issue discussed in this paper.
Mentions: From all we have learned above, any microRNA that modulates any of the many factors regulating GC-induced apoptosis may affect the apoptotic response to GCs (Figures 1–6). These include microRNAs that affect GR expression (e.g., miR-18, miR-124a, miR-130b, miR-142, and miR-181a), those affecting Bim expression (miR-26a, miR-93, miR-17~92, miR-106a~363, and miR-106b~25) or its transcription factor FoxO3 (e.g., miR-1, miR-21, miR-27a, miR-96, miR-135b, miR-155, and miR-182), those affecting PTEN expression (miR-17~92, miR-106b~25, miR-21, miR-26a, miR-29b, miR-214, miR-216a, miR-217, miR-221, and miR-222) or mTOR (e.g., miR-101), and those downregulating directly or indirectly the anti-apoptotic proteins Bcl-2, Bcl-XL, Mcl-1, XIAP, and CYLD (e.g., miR-15a~16, miR-181a/b, miR-34a, miR-125b, miR-29a/b/c, miR-101, miR-133b, miR-193b, miR-512, let-7, and miR-491). The effect of some of these microRNAs on GC-sensitivity has already been described above and will not be repeated here. Rather, I will present here some data from primary samples showing the influence of microRNAs on clinical outcome.

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