miR-150 downregulation contributes to the high-grade
transformation of follicular lymphoma by upregulating FOXP1
levels

J 2018

miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels

MUSILOVÁ, Kateřina, Ján DEVÁN, Kateřina AMRUZ ČERNÁ, Václav ŠEDA, Gabriela PAVLASOVÁ et. al.

Basic information

Original name

miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels

Authors

MUSILOVÁ, Kateřina (203 Czech Republic, belonging to the institution), Ján DEVÁN (703 Slovakia, belonging to the institution), Kateřina AMRUZ ČERNÁ (203 Czech Republic, belonging to the institution), Václav ŠEDA (203 Czech Republic, belonging to the institution), Gabriela PAVLASOVÁ (203 Czech Republic, belonging to the institution), Sonali SHARMA (356 India, belonging to the institution), Jan OPPELT (203 Czech Republic, belonging to the institution), R. PYTLIK (203 Czech Republic), V. PROCHAZKA (203 Czech Republic), Z. PROUZOVA (203 Czech Republic), Martin TRBUŠEK (203 Czech Republic, belonging to the institution), L. ZLAMALIKOVA (203 Czech Republic), K. LISKOVA (203 Czech Republic), L. KRUZOVA (203 Czech Republic), M. JAROSOVA (203 Czech Republic), Andrea MAREČKOVÁ (203 Czech Republic), C. KORNAUTH (40 Austria), I. SIMONITSCH-KLUPP (40 Austria), A.I. SCHIEFER (40 Austria), O. MERKEL (40 Austria), H. MOCIKOVA (203 Czech Republic), P. BURDA (203 Czech Republic), K.M. POLAKOVA (203 Czech Republic), L. KREN (203 Czech Republic), Jiří MAYER (203 Czech Republic, belonging to the institution), C.S. ZENT (840 United States of America), M. TRNENY (203 Czech Republic), A.G. EVANS (840 United States of America), Andrea JANÍKOVÁ (203 Czech Republic, belonging to the institution) and Marek MRÁZ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Blood, Washington DC, USA, American Society of Hematology, 2018, 0006-4971

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 16.601

RIV identification code

RIV/00216224:14740/18:00105661

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1182/blood-2018-06-855502

UT WoS

000451634400012

Keywords in English

B-CELL LYMPHOMA; TRANSCRIPTION FACTOR; T-CELLS; C-MYC; HISTOLOGIC TRANSFORMATION; COPY-NUMBER; KAPPA-B; EXPRESSION; SURVIVAL; MICRORNAS

Abstract

V originále

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.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

NV16-29622A, research and development project

Name: VLIV TERAPEUTICKÉ INHIBICE BCR SIGNALIZACE NA GENOVOU EXPRESI U B BUNĚČNÝCH MALIGNIT A JEJÍ PROGNOSTICKÝ A PREDIKTIVNÍ VÝZNAM

NV18-03-00054, research and development project

Name: ÚLOHA MICRORNA A JEJICH CÍLOVÝCH MOLEKUL V TRANSFORMACI FOLIKULÁRNÍHO LYMFOMU A AGRESIVITĚ CHRONICKÉ LYMFOCYTÁRNÍ LEUKÉMIE

Investor: Ministry of Health of the CR

Citovat

MUSILOVÁ, Kateřina, Ján DEVÁN, Kateřina AMRUZ ČERNÁ, Václav ŠEDA, Gabriela PAVLASOVÁ, Sonali SHARMA, Jan OPPELT, R. PYTLIK, V. PROCHAZKA, Z. PROUZOVA, Martin TRBUŠEK, L. ZLAMALIKOVA, K. LISKOVA, L. KRUZOVA, M. JAROSOVA, Andrea MAREČKOVÁ, C. KORNAUTH, I. SIMONITSCH-KLUPP, A.I. SCHIEFER, O. MERKEL, H. MOCIKOVA, P. BURDA, K.M. POLAKOVA, L. KREN, Jiří MAYER, C.S. ZENT, M. TRNENY, A.G. EVANS, Andrea JANÍKOVÁ and Marek MRÁZ. miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels. Blood. Washington DC, USA: American Society of Hematology, 2018, vol. 132, No 22, p. 2389-2400. ISSN 0006-4971. Available from: https://dx.doi.org/10.1182/blood-2018-06-855502.

@article{1488089,
   author = {Musilová, Kateřina and Deván, Ján and Amruz Černá, Kateřina and Šeda, Václav and Pavlasová, Gabriela and Sharma, Sonali and Oppelt, Jan and Pytlik, R. and Prochazka, V. and Prouzova, Z. and Trbušek, Martin and Zlamalikova, L. and Liskova, K. and Kruzova, L. and Jarosova, M. and Marečková, Andrea and Kornauth, C. and SimonitschandKlupp, I. and Schiefer, A.I. and Merkel, O. and Mocikova, H. and Burda, P. and Polakova, K.M. and Kren, L. and Mayer, Jiří and Zent, C.S. and Trneny, M. and Evans, A.G. and Janíková, Andrea and Mráz, Marek},
   article_location = {Washington DC, USA},
   article_number = {22},
   doi = {http://dx.doi.org/10.1182/blood-2018-06-855502},
   keywords = {B-CELL LYMPHOMA; TRANSCRIPTION FACTOR; T-CELLS; C-MYC; HISTOLOGIC TRANSFORMATION; COPY-NUMBER; KAPPA-B; EXPRESSION; SURVIVAL; MICRORNAS},
   language = {eng},
   issn = {0006-4971},
   journal = {Blood},
   title = {miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels},
   url = {http://www.bloodjournal.org/content/132/22/2389?sso-checked=true},
   volume = {132},
   year = {2018}
}

TY  - JOUR
ID  - 1488089
AU  - Musilová, Kateřina - Deván, Ján - Amruz Černá, Kateřina - Šeda, Václav - Pavlasová, Gabriela - Sharma, Sonali - Oppelt, Jan - Pytlik, R. - Prochazka, V. - Prouzova, Z. - Trbušek, Martin - Zlamalikova, L. - Liskova, K. - Kruzova, L. - Jarosova, M. - Marečková, Andrea - Kornauth, C. - Simonitsch-Klupp, I. - Schiefer, A.I. - Merkel, O. - Mocikova, H. - Burda, P. - Polakova, K.M. - Kren, L. - Mayer, Jiří - Zent, C.S. - Trneny, M. - Evans, A.G. - Janíková, Andrea - Mráz, Marek
PY  - 2018
TI  - miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels
JF  - Blood
VL  - 132
IS  - 22
SP  - 2389-2400
EP  - 2389-2400
PB  - American Society of Hematology
SN  - 00064971
KW  - B-CELL LYMPHOMA
KW  - TRANSCRIPTION FACTOR
KW  - T-CELLS
KW  - C-MYC
KW  - HISTOLOGIC TRANSFORMATION
KW  - COPY-NUMBER
KW  - KAPPA-B
KW  - EXPRESSION
KW  - SURVIVAL
KW  - MICRORNAS
UR  - http://www.bloodjournal.org/content/132/22/2389?sso-checked=true
N2  - 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.
ER  -

MUSILOVÁ, Kateřina, Ján DEVÁN, Kateřina AMRUZ ČERNÁ, Václav ŠEDA, Gabriela PAVLASOVÁ, Sonali SHARMA, Jan OPPELT, R. PYTLIK, V. PROCHAZKA, Z. PROUZOVA, Martin TRBUŠEK, L. ZLAMALIKOVA, K. LISKOVA, L. KRUZOVA, M. JAROSOVA, Andrea MAREČKOVÁ, C. KORNAUTH, I. SIMONITSCH-KLUPP, A.I. SCHIEFER, O. MERKEL, H. MOCIKOVA, P. BURDA, K.M. POLAKOVA, L. KREN, Jiří MAYER, C.S. ZENT, M. TRNENY, A.G. EVANS, Andrea JANÍKOVÁ and Marek MRÁZ. miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels. \textit{Blood}. Washington DC, USA: American Society of Hematology, 2018, vol.~132, No~22, p.~2389-2400. ISSN~0006-4971. Available from: https://dx.doi.org/10.1182/blood-2018-06-855502.

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