microRNA-181a enhances cell proliferation in acute lymphoblastic leukemia by targeting EGR1

Verduci, Lorena; Azzalin, Gianluca; Gioiosa, Silvia; Carissimi, Claudia; Laudadio, Ilaria; Fulci, Valerio; Macino, Giuseppe

doi:10.1016/j.leukres.2015.01.010

Cited by 63 publications

(54 citation statements)

References 38 publications

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“…The longest LRCs are composed of 14 TFs and one non-TF gene ( Figure 5B and C, and Figure 6A). Interestingly, the 'tail' of the longest LRCs contains several genes that are often dysregulated in cancer: EGR1 (33)(34)(35), IRF3 (36), POLR3A (37) and IRF1 (38,39).…”

Section: Computational Analysis Of Lrcs In Human Cell Linesmentioning

confidence: 99%

Universal attenuators and their interactions with feedback loops in gene regulatory networks

Liu

Albergante

Newman

2016

Preprint

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Using a combination of mathematical modelling, statistical simulation and large-scale data analysis we study the properties of linear regulatory chains (LRCs) within gene regulatory networks (GRNs). Our modelling indicates that downstream genes embedded within LRCs are highly insulated from the variation in expression of upstream genes, and thus LRCs act as attenuators. This observation implies a progressively weaker functionality of LRCs as their length increases. When analyzing the preponderance of LRCs in the GRNs of Escherichia coli K12 and several other organisms, we find that very long LRCs are essentially absent. In both E. coli and M. tuberculosis we find that four-gene LRCs are intimately linked to identical feedback loops that are involved in potentially chaotic stress response, indicating that the dynamics of these potentially destabilising motifs are strongly restrained under homeostatic conditions. The same relationship is observed in a human cancer cell line (K562), and we postulate that four-gene LRCs act as 'universal attenuators'. These findings suggest a role for long LRCs in dampening variation in gene expression, thereby protecting cell identity, and in controlling dramatic shifts in cell-wide gene expression through inhibiting chaos-generating motifs.

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Section: Computational Analysis Of Lrcs In Human Cell Linesmentioning

confidence: 99%

Universal attenuators and their interactions with feedback loops in gene regulatory networks

Liu

Albergante

Newman

2016

Preprint

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“…MiR-181a was recently shown to be consistently overexpressed in T-cell leukemia and lymphoma [39]. Over-expression of miR-181a also correlated with chemotherapeutic resistance, tumor progression, and advanced disease in these cancers [31, 38, 44, 45]. The anti-apoptotic protein Bcl-2 is a target of miR-181a/b, which contributes to tumor resistance to apoptosis in CLL [31].…”

Section: Discussionmentioning

confidence: 99%

“…The miR-181 family includes four members (miR-181a-d) produced from three polycistronic clusters [23, 35]. MiR-181 is dysregulated in many cancers [36–38], including function as a tumor suppressor in CLL [39], and as an oncogene in breast [40] and colorectal cancers [36]. MiR-181 also plays a significant role in T-cell development and differentiation [23, 27, 35, 36, 41].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients

et al. 2017

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Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that is characterized by aggressive spread of neoplastic CD4+ T-cells from the skin into the bloodstream with metastasis to visceral organs. The deoxynucleoside triphosphohydrolase SAMHD1 is highly expressed in normal CD4+ T-cells, while its expression is down-regulated in CD4+ T-cells from SS patients. MicroRNA (miR) dysregulation is an important epigenetic mechanism in the pathogenesis and progression of SS. MiR-181 has been shown to inhibit SAMHD1 expression in cell lines and was identified as an important prognostic biomarker in CTCL. However, whether SAMHD1 is down-regulated by miR-181 in primary CD4+ T-cells of SS patients is unknown. Compared to normal CD4+ T-cells, SAMHD1 protein expression is significantly reduced in transformed CD4+ T-cell lines and CD4+ T-cells from SS patients, which inversely correlates with increased miR-181 levels in these cells. Over-expression of miR-181b in primary CD4+ T-cells from healthy donors significantly decreased SAMHD1 protein level, but not mRNA level. In contrast, inhibition of miR-181 in a CD4+ T-cell line significantly increased the level of SAMHD1 protein expression. Our results demonstrate that miR-181 is an important regulator of SAMHD1 protein expression in neoplastic CD4+ T-cells, likely through a mechanism of translational inhibition.

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“…A second example is the negative correlation between miR - 181a and EGR1 , a tumor suppressor in several other cancer entities. The miR - 181a / EGR1 pair probably has a role in cell cycle regulation [128]. miR - 181a is also linked to the NOTCH1 signaling pathway which is discussed further in more detail [129].…”

Section: Oncomirs and Tumor Suppressor Mirnas In T-allmentioning

confidence: 99%

T-ALL and thymocytes: a message of noncoding RNAs

et al. 2017

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In the last decade, the role for noncoding RNAs in disease was clearly established, starting with microRNAs and later expanded towards long noncoding RNAs. This was also the case for T cell acute lymphoblastic leukemia, which is a malignant blood disorder arising from oncogenic events during normal T cell development in the thymus. By studying the transcriptomic profile of protein-coding genes, several oncogenic events leading to T cell acute lymphoblastic leukemia (T-ALL) could be identified. In recent years, it became apparent that several of these oncogenes function via microRNAs and long noncoding RNAs. In this review, we give a detailed overview of the studies that describe the noncoding RNAome in T-ALL oncogenesis and normal T cell development.

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microRNA-181a enhances cell proliferation in acute lymphoblastic leukemia by targeting EGR1

Cited by 63 publications

References 38 publications

Universal attenuators and their interactions with feedback loops in gene regulatory networks

Universal attenuators and their interactions with feedback loops in gene regulatory networks

MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients

T-ALL and thymocytes: a message of noncoding RNAs

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