Oncogenic microRNA-155 and its target PU.1: an integrative gene expression study in six of the most prevalent lymphomas.
The transcription factor PU.1 and its inhibitory microRNA-155 (miR-155) are important regulators of B-cell differentiation. PU.1 downregulation coupled with oncogenic miR-155 upregulation has been reported in lymphoid malignancies; however, these data have not been studied across different subtypes in relation to clinical outcomes. We studied expression of miR-155 and PU.1 in the six most prevalent human B-cell lymphomas (n = 131) including aggressive (DLBCL, HL, MCL) and indolent (B-CLL/SLL, MZL, FL) types. Levels of miR-155 and PU.1 inversely correlated in DLBCL, B-CLL/SLL, and FL tumor tissues. In HL tissues, an exceptionally high level of miR-155 was found in patients with unfavorable responses to first-line therapy and those who had shorter survival times. PU.1 downregulation was noted in B-CLL/SLL samples positive for the adverse prognostic markers CD38 and ZAP-70. Upregulation of miR-155 and downregulation of PU.1 expression are integral aspects of lymphoma biology that could mark aggressive behavior of some, but not all, lymphoma types.
Institute of Pathological Physiology, 1st Medical Faculty, Charles University in Prague, U Nemocnice 5, 128 53, Prague, Czech Republic.
Hana
H
Huskova
1st Medical Department - Hematology, General Faculty Hospital, U Nemocnice 2, 128 08, Prague, Czech Republic.
Katarina
K
Korecka
1st Medical Department - Hematology, General Faculty Hospital, U Nemocnice 2, 128 08, Prague, Czech Republic.
Josef
J
Karban
Institute of Pathological Physiology, 1st Medical Faculty, Charles University in Prague, U Nemocnice 5, 128 53, Prague, Czech Republic.
Jarmila
J
Vargova
Institute of Pathological Physiology, 1st Medical Faculty, Charles University in Prague, U Nemocnice 5, 128 53, Prague, Czech Republic.
Karina
K
Vargova
Institute of Pathological Physiology, 1st Medical Faculty, Charles University in Prague, U Nemocnice 5, 128 53, Prague, Czech Republic.
Nina
N
Dusilkova
1st Medical Department - Hematology, General Faculty Hospital, U Nemocnice 2, 128 08, Prague, Czech Republic.
Marek
M
Trneny
Institute of Pathological Physiology, 1st Medical Faculty, Charles University in Prague, U Nemocnice 5, 128 53, Prague, Czech Republic. tstopka@lf1.cuni.cz.|1st Medical Department - Hematology, General Faculty Hospital, U Nemocnice 2, 128 08, Prague, Czech Republic. tstopka@lf1.cuni.cz.
Tomas
T
Stopka
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008223:Lymphoma / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D015534:Trans-Activators / Q000096:biosynthesis*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D051997:ADP-ribosyl Cyclase 1; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D015534:Trans-Activators; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099232:Proto-Oncogene Protein Spi-1; C524942:MIRN155 microRNA, human; C497261:ZAP70 protein, human
Lymphoma; PU.1; Prognosis; microRNA miR-155