miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F18%3A00069101" target="_blank" >RIV/65269705:_____/18:00069101 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/18:00105661 RIV/00216208:11110/18:10384245 RIV/00216208:11120/18:43917064 RIV/00064173:_____/18:N0000151 and 3 more
Result on the web
<a href="http://dx.doi.org/10.1182/blood-2018-06-855502" target="_blank" >http://dx.doi.org/10.1182/blood-2018-06-855502</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/blood-2018-06-855502" target="_blank" >10.1182/blood-2018-06-855502</a>
Alternative languages
Result language
angličtina
Original language name
miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels
Original language description
Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations ofMYC or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely miR-150, which was uniformly downmodulated in all examined tFLs (similar to 3.5-fold), and observed that high levels of MYC are responsible for repressing miR-150 in tFL by binding in its upstream region. This MYC-mediated repression of miR-150 in B cells is not dependent on LIN28A/B proteins, which influence the maturation of miR-150 precursor (pri-miR-150) in myeloid cells. We also demonstrated that low miR-150 levels in tFL lead to upregulation of its target, namely FOXP1 protein, which is a known positive regulator of cell survival, as well as B-cell receptor and NF-kappa B signaling in malignant B cells. We revealed that low levels of miR-150 and high levels of its target, FOXP1, are associated with shorter overall survival in FL and suggest that miR-150 could serve as a good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall, our study demonstrates the role of theMYC/miR-150/FOXP1 axis in malignant B cells as a determinant of FL aggressiveness and its high-grade transformation.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood
ISSN
0006-4971
e-ISSN
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Volume of the periodical
132
Issue of the periodical within the volume
22
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
2389-2400
UT code for WoS article
000451634400012
EID of the result in the Scopus database
2-s2.0-85057234268