title: miR-155 regulates HGAL expression and increases lymphoma cell motility.
abstract: HGAL, a prognostic biomarker in patients with diffuse large B-cell lymphoma and classic Hodgkin lymphoma, inhibits lymphocyte and lymphoma cell motility by activating the RhoA signaling cascade and interacting with actin and myosin proteins. Although HGAL expression is limited to germinal center (GC) lymphocytes and GC-derived lymphomas, little is known about its regulation. miR-155 is implicated in control of GC reaction and lymphomagenesis. We demonstrate that miR-155 directly down-regulates HGAL expression by binding to its 3'-untranslated region, leading to decreased RhoA activation and increased spontaneous and chemoattractant-induced lymphoma cell motility. The effects of miR-155 on RhoA activation and cell motility can be rescued by transfection of HGAL lacking the miR-155 binding site. This inhibitory effect of miR-155 suggests that it may have a key role in the loss of HGAL expression on differentiation of human GC B cells to plasma cell. Furthermore, this effect may contribute to lymphoma cell dissemination and aggressiveness, characteristic of activated B cell-like diffuse large B-cell lymphoma typically expressing high levels of miR-155 and lacking HGAL expression.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, FL 33136, USA.
authors.forename: Liat Nadav
authors.initials: LN
authors.lastname: Dagan
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jiang
authors.forename: Shruti
authors.initials: S
authors.lastname: Bhatt
authors.forename: Elena
authors.initials: E
authors.lastname: Cubedo
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D005434:Flow Cytometry; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008840:Microfilament Proteins; D016296:Mutagenesis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C476824:GCSAM protein, human; D047908:Intracellular Signaling Peptides and Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; C532623:Mirn155 microRNA, mouse; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D008156:Luciferases; D020742:rhoA GTP-Binding Protein
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