6 research outputs found
Impaired expression of DICER, DROSHA, SBDS and some microRNAs in mesenchymal stromal cells from myelodysplastic syndrome patients
This is an open-access paper.[Background]: Recent findings suggest that a specific deletion of Dicer1 in mesenchymal stromal cells-derived
osteoprogenitors triggers several features of myelodysplastic syndrome in a murine model. Our
aim was to analyze DICER1 and DROSHA gene and protein expression in mesenchymal stromal
cells (the osteoblastic progenitors) obtained from bone marrow of myelodysplastic syndrome
patients, in addition to microRNA expression profile and other target genes such as SBDS, a
DICER1-related gene that promotes bone marrow dysfunction and myelodysplasia when
repressed in a murine model.
[Design and Methods]: Mesenchymal stromal cells from 33 bone marrow samples were evaluated. DICER, DROSHA and
SBDS gene expression levels were assessed by real-time PCR and protein expression by Western
blot. MicroRNA expresion profile was analyzed by commercial low-density arrays and some of
these results were confirmed by individual real-time PCR.
[Results]: Mesenchymal stromal cells from myelodysplastic syndrome patients showed lower DICER1
(0.65±0.08 vs. 1.91±0.57; P=0.011) and DROSHA (0.62±0.06 vs. 1.38±0.29; P=0.009) gene expression
levels, two relevant endonucleases associated to microRNA biogenesis, in comparison to normal
myelodysplastic syndrome. These findings were confirmed at protein levels by Western blot.
Strikingly, no differences were observed between paired mononuclear cells from myelodysplastic
syndrome and controls. In addition, mesenchymal stromal cells from myelodysplastic syndrome
patients showed significant lower SBDS (0.63±0.06 vs. 1.15±0.28; P=0.021) gene expression levels
than mesenchymal stromal cells from healthy controls. Furthermore, mesenchymal stromal
cells from myelodysplastic syndrome patients showed an underlying microRNA repression compared
to healthy controls. Real-time PCR approach confirmed that mir-155, miR-181a and miR-
222 were down-expressed in mesenchymal stromal cells from myelodysplastic syndrome
patients.
[Conclusions]: This is the first description of an impaired microRNA biogenesis in human mesenchymal stromal
cells from myelodysplastic syndrome patients, where DICER1 and DROSHA gene and protein
downregulation correlated to a gene and microRNA abnormal expression profile, validating
the animal model results previously described.Grants from Consejeria de Educacion de la Junta de Castilla y León (HUS03A09) and Instituto de
Salud Carlos III (FIS09/01530).Peer reviewe
Orthographic learning in Spanish children: influence of previous semantic and phonological knowledge
This study was funded by Grant PSI2015-64174-P from the Spanish Government and sup-ported by the predoctoral grant BP14-038 from the Foundation for the Promotion of Ap-plied Scientific Research and Technology in Asturias (FICYT