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.

Základní údaje

Originální název

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

Autoři

MUSILOVÁ, Kateřina (203 Česká republika, domácí), Ján DEVÁN (703 Slovensko, domácí), Kateřina AMRUZ ČERNÁ (203 Česká republika, domácí), Václav ŠEDA (203 Česká republika, domácí), Gabriela PAVLASOVÁ (203 Česká republika, domácí), Sonali SHARMA (356 Indie, domácí), Jan OPPELT (203 Česká republika, domácí), R. PYTLIK (203 Česká republika), V. PROCHAZKA (203 Česká republika), Z. PROUZOVA (203 Česká republika), Martin TRBUŠEK (203 Česká republika, domácí), L. ZLAMALIKOVA (203 Česká republika), K. LISKOVA (203 Česká republika), L. KRUZOVA (203 Česká republika), M. JAROSOVA (203 Česká republika), Andrea MAREČKOVÁ (203 Česká republika), C. KORNAUTH (40 Rakousko), I. SIMONITSCH-KLUPP (40 Rakousko), A.I. SCHIEFER (40 Rakousko), O. MERKEL (40 Rakousko), H. MOCIKOVA (203 Česká republika), P. BURDA (203 Česká republika), K.M. POLAKOVA (203 Česká republika), L. KREN (203 Česká republika), Jiří MAYER (203 Česká republika, domácí), C.S. ZENT (840 Spojené státy), M. TRNENY (203 Česká republika), A.G. EVANS (840 Spojené státy), Andrea JANÍKOVÁ (203 Česká republika, domácí) a Marek MRÁZ (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 16.601

Kód RIV

RIV/00216224:14740/18:00105661

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000451634400012

Klíčová slova anglicky

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

Štítky

14110212, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 3. 2019 16:23, Mgr. Pavla Foltynová, Ph.D.

Anotace

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.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

NV16-29622A, projekt VaV

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

NV18-03-00054, projekt VaV

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

Investor: Ministerstvo zdravotnictví ČR, ÚLOHA MICRORNA A JEJICH CÍLOVÝCH MOLEKUL V TRANSFORMACI FOLIKULÁRNÍHO LYMFOMU A AGRESIVITĚ CHRONICKÉ LYMFOCYTÁRNÍ LEUKÉMIE

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 a 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, roč. 132, č. 22, s. 2389-2400. ISSN 0006-4971. Dostupné z: 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 a 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, roč.~132, č.~22, s.~2389-2400. ISSN~0006-4971. Dostupné z: https://dx.doi.org/10.1182/blood-2018-06-855502.

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