MicroRNAs Modulate Hematopoietic Lineage Differentiation

Abstract

MicroRNAs (miRNAs), an abundant class of 22 nucleotide non-coding RNAs, are thought to play an important regulatory role in animal and plant development at the posttranscriptional level. Many miRNAs cloned from mouse bone marrow cells are differentially regulated in various hematopoietic lineages, suggesting that they might influence hematopoietic lineage differentiation. Some human miRNAs are linked to leukemias: the miR-15a/miR-16 locus is frequently deleted or down-regulated in patients with B-cell chronic lymphocytic leukemia and miR-142 is at a translocation site found in a case of aggressive B-cell leukemia. miR-181, a miRNA upregulated only in the B cell lineage of mouse bone marrow cells, promotes B cell differentiation and inhibits production of CD8 + T cells when expressed in hematopoietic stem/progenitor cells. In contrast miR142s inhibits production of both CD4 + and CD8 + T cells and does not affect B cells. Collectively, these results indicate that microRNAs are components of the molecular circuitry controlling mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development.

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

“…In fact, we demonstrated that NF-kB (p50/p50), but not p65/p50 binds to the upstream sequence of the let-7a-3/let7b cluster and activates its transcription. Previous work by The results are shown as relative fold change in the miRNA expression with respect to the control (untreated) NB4 cells miRNA levels, after normalization with 18 s and 2 (ÀD-Ct) calculations as described previously (Chen et al, 2004). (b) Confirmation of successful NF-kB inhibition.…”

“…There is also evidence that supports a role for miRNAs in hematopoiesis. In mice, miR-181a is detected in early progenitor cells and dynamically upregulated during B-cell commitment (Chen et al, 2004). Furthermore, the ectopic expression of miR-181a in murine hematopoietic progenitor cells led to a proliferation in the B-cell compartment (Chen et al, 2004).…”

“…In mice, miR-181a is detected in early progenitor cells and dynamically upregulated during B-cell commitment (Chen et al, 2004). Furthermore, the ectopic expression of miR-181a in murine hematopoietic progenitor cells led to a proliferation in the B-cell compartment (Chen et al, 2004). More recently, it has been reported that miR-223 is a key member of a regulatory circuit involving C/EBPa and NFI-A that controls granulocytic differentiation in ATRA-treated APL cell lines (Fazi et al, 2005).…”

NDAMDA: Network distance analysis for MiRNA‐disease association prediction

“…Asince the lin‐4 and let‐7 were discovered in Caenorhabditis elegans ,4 over 30 000 mature miRNAs have been found from 206 species 5. Furthermore, accumulating evidence shows that miRNA constitutes one of the most important components of cells and is involved in nearly all biological processes, including cell growth,6 immune reaction,7 cell proliferation and differentiation,8, 9 cell development,6 cell cycle regulation,10 inflammation,11 apoptosis 12 and stress response 6, 13. It is also reported that the abnormality of miRNAs is connected with various human diseases, particularly cancers 14, 15.…”

Des microARN comme s’il en pleuvait…

“…Chez la drosophile, plusieurs miARN (miR-14, bantam, miR-2) contrôlent la prolifération et/ou la différenciation cellulaires en modulant notamment l'expression de gènes proapoptotiques comme hid (Tableau I) [13]. Chez les mammifères, bien que sa cible reste à identifier, miR-181 interviendrait lors du processus de différenciation hématopoïétique [14]. Il ne faut pas non plus écarter l'hypothèse d'un dérèglement de l'expression des miARN dans les processus d'oncogenèse, et certaines translocations chromosomiques associées à des leucémies affectent des locus géniques comportant les gènes miR-142, miR-15, miR-16, miR-155 (pour revue, voir [15,16]).…”