title: Regulation of JAK2 by miR-135a: prognostic impact in classic Hodgkin lymphoma.
abstract: The behavior of classic Hodgkin lymphoma (cHL) is determined by both the intrinsic features of the tumor cells and the characteristics of the microenvironment, making the analysis of entire lymph nodes an effective approach to understanding the disease. We examined the influence of our previously reported 25-microRNA signature for cHL on clinical outcome in 89 homogeneously treated cHL patients with a median follow-up of 80 months. Patients with low miR-135a expression had a higher probability of relapse (P = .04) and a shorter disease-free survival (P = .02). Functional analysis of cHL cell lines showed that mature miR-135a levels increased after pre-miR-135a transfection, causing apoptosis and decreased cell growth. Target analysis showed a direct regulation by miR-135a of JAK2, a cytoplasmic tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. miR-135a-mediated JAK2 down-regulation led to decreased mRNA and protein levels of the antiapoptotic gene Bcl-xL, suggesting a role for Bcl-xL in miR-135a/JAK2-mediated apoptosis. Our findings confirm the critical role of miR-135a in the survival of cHL cells and in the prognosis of cHL patients, indicating that novel treatment approaches targeting miR-135a may potentially benefit these patients.
authors: Human Anatomy Unit, Molecular Oncology and Embryology Laboratory, University of Barcelona Medical School, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors: Alfons
authors: A
authors: Navarro
authors: Tania
authors: T
authors: Diaz
authors: Antonio
authors: A
authors: Martinez
authors: Anna
authors: A
authors: Gaya
authors: Aina
authors: A
authors: Pons
authors: Bernat
authors: B
authors: Gel
authors: Carles
authors: C
authors: Codony
authors: Gerardo
authors: G
authors: Ferrer
authors: Carmen
authors: C
authors: Martinez
authors: Emili
authors: E
authors: Montserrat
authors: Mariano
authors: M
authors: Monzo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection; D055815:Young Adult
chemical_list: C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases; C507924:JAK2 protein, human; D053614:Janus Kinase 2