title: Methylation of miR-155-3p in mantle cell lymphoma and other non-Hodgkin's lymphomas.
abstract: Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma (NHL). In cancers, tumor suppressive microRNAs may be silenced by DNA hypermethylation. By microRNA profiling of representative EBV-negative MCL cell lines before and after demethylation treatment, miR-155-3p was found significantly restored. Methylation-specific PCR, verified by pyrosequencing, showed complete methylation of miR-155-3p in one MCL cell line (REC-1). 5-aza-2'-deoxycytidine treatment of REC-1 led to demethylation and re-expression of miR-155-3p. Over-expression of miR-155-3p led to increased sub-G1 apoptotic cells and reduced cellular viability, demonstrating its tumor suppressive properties. By luciferase assay, lymphotoxin-beta (LT-β) was validated as a miR-155-3p target. In 31 primary MCL, miR-155-3p was found hypermethylated in 6(19%) cases. To test if methylation of miR-155-3p was MCL-specific, miR-155-3p methylation was tested in an additional 191 B-cell, T-cell and NK-cell NHLs, yielding miR-155-3p methylation in 66(34.6%) including 36(27%) non-MCL B-cell, 24(53%) T-cell and 6(46%) of NK-cell lymphoma. Moreover, in 72 primary NHL samples with RNA, miR-155-3p methylation correlated with miR-155-3p downregulation (p=0.024), and LT-β upregulation (p=0.043). Collectively, miR-155-3p is a potential tumor suppressive microRNA hypermethylated in MCL and other NHL subtypes. As miR-155-3p targets LT-β, which is an upstream activator of the non-canonical NF-kB signaling, miR-155-3p methylation is potentially important in lymphomagenesis.
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors.forename: Rita Lh
authors.initials: RL
authors.lastname: Yim
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors.forename: Kwan Yeung
authors.initials: KY
authors.lastname: Wong
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors.forename: Yok Lam
authors.initials: YL
authors.lastname: Kwong
authors.affiliation: Department of Pathology, Queen Mary Hospital, Hong Kong.
authors.forename: Florence
authors.initials: F
authors.lastname: Loong
authors.affiliation: Department of Pathology, United Christian Hospital, Hong Kong.
authors.forename: Chung Ying
authors.initials: CY
authors.lastname: Leung
authors.affiliation: Department of Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong.
authors.forename: Raymond
authors.initials: R
authors.lastname: Chu
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong.
authors.forename: William Wai Lung
authors.initials: WW
authors.lastname: Lam
authors.affiliation: Department of Pathology, Kwong Wah Hospital, Hong Kong.
authors.forename: Pak Kwan
authors.initials: PK
authors.lastname: Hui
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
authors.forename: Chor Sang
authors.initials: CS
authors.lastname: Chim
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism; D053308:Lymphotoxin-beta / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: C505886:LTB protein, human; D053308:Lymphotoxin-beta; C524942:MIRN155 microRNA, human; D035683:MicroRNAs