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2015 ; 10
(10
): e0140445
Nephropedia Template TP
gab.com Text
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English Wikipedia
Small RNA Sequencing Uncovers New miRNAs and moRNAs Differentially Expressed in
Normal and Primary Myelofibrosis CD34+ Cells
#MMPMID26468945
Guglielmelli P
; Bisognin A
; Saccoman C
; Mannarelli C
; Coppe A
; Vannucchi AM
; Bortoluzzi S
PLoS One
2015[]; 10
(10
): e0140445
PMID26468945
show ga
Myeloproliferative neoplasms (MPN) are chronic myeloid cancers thought to arise
at the level of CD34+ hematopoietic stem/progenitor cells. They include essential
thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). All
can progress to acute leukemia, but PMF carries the worst prognosis. Increasing
evidences indicate that deregulation of microRNAs (miRNAs) might plays an
important role in hematologic malignancies, including MPN. To attain deeper
knowledge of short RNAs (sRNAs) expression pattern in CD34+ cells and of their
possible role in mediating post-transcriptional regulation in PMF, we sequenced
with Illumina HiSeq2000 technology CD34+ cells from healthy subjects and PMF
patients. We detected the expression of 784 known miRNAs, with a prevalence of
miRNA up-regulation in PMF samples, and discovered 34 new miRNAs and 99 new
miRNA-offset RNAs (moRNAs), in CD34+ cells. Thirty-seven small RNAs were
differentially expressed in PMF patients compared with healthy subjects,
according to microRNA sequencing data. Five miRNAs (miR-10b-5p, miR-19b-3p,
miR-29a-3p, miR-379-5p, and miR-543) were deregulated also in PMF granulocytes.
Moreover, 3'-moR-128-2 resulted consistently downregulated in PMF according to
RNA-seq and qRT-PCR data both in CD34+ cells and granulocytes. Target predictions
of these validated small RNAs de-regulated in PMF and functional enrichment
analyses highlighted many interesting pathways involved in tumor development and
progression, such as signaling by FGFR and DAP12 and Oncogene Induced Senescence.
As a whole, data obtained in this study deepened the knowledge of miRNAs and
moRNAs altered expression in PMF CD34+ cells and allowed to identify and validate
a specific small RNA profile that distinguishes PMF granulocytes from those of
normal subjects. We thus provided new information regarding the possible role of
miRNAs and, specifically, of new moRNAs in this disease.
|Adaptor Proteins, Signal Transducing/genetics/metabolism
[MESH]