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Expression of <jats:italic>MIR129<\/jats:italic> and its target, <jats:italic>SOX4<\/jats:italic>, in cell lines was measured before and after hypomethylating treatment and <jats:italic>MIR129<\/jats:italic> overexpression. <jats:italic>MIR129<\/jats:italic> expression was correlated with <jats:italic>MIR129-2<\/jats:italic> methylation status in primary lymphoma samples. Tumor suppressor function of <jats:italic>MIR129<\/jats:italic> was demonstrated by MTT and trypan blue exclusion assay after <jats:italic>MIR129<\/jats:italic> overexpression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The sensitivity of the methylated-MSP was one in 10<jats:sup>3<\/jats:sup>. Different MSP statuses, including complete methylation, partial methylation, and complete unmethylation, were verified by quantitative bisulfite pyrosequencing. All five lymphoma and seven of eight myeloma cell lines showed complete and partial <jats:italic>MIR129-2<\/jats:italic> methylation. In primary samples, <jats:italic>MIR129-2<\/jats:italic> methylation was absent in AML and CML, but detected in 5% ALL, 45.9% CLL, 49.5% MM at diagnosis, and 59.1% NHL. In CLL, <jats:italic>MIR129-2<\/jats:italic> methylation adversely impacted on survival (p=0.004). In MM, <jats:italic>MIR129-2<\/jats:italic> methylation increased from 27.5% MGUS to 49.5% MM at diagnosis and 41.5% at relapse\/progression (p=0.023). In NHL, <jats:italic>MIR129-2<\/jats:italic> methylation was associated with <jats:italic>MIR124-1<\/jats:italic> and <jats:italic>MIR203<\/jats:italic> methylation (p&lt;0.001), and lower <jats:italic>MIR129<\/jats:italic> expression (p=0.009). Hypomethylation treatment of JEKO-1, homozygously methylated for <jats:italic>MIR129-2<\/jats:italic>, led to <jats:italic>MIR129-2<\/jats:italic> demethylation and <jats:italic>MIR129<\/jats:italic> re-expression, with downregulation of <jats:italic>SOX4<\/jats:italic> mRNA. Moreover, <jats:italic>MIR129<\/jats:italic> overexpression in both mantle cell lines, JEKO-1 and GRANTA-519, inhibited cellular proliferation and enhanced cell death, with concomitant <jats:italic>SOX4<\/jats:italic> mRNA downregulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              <jats:italic>MIR129-2<\/jats:italic> is a tumor suppressive microRNA frequently methylated in lymphoid but not myeloid malignancies, leading to reversible <jats:italic>MIR129-2<\/jats:italic> silencing. In CLL, <jats:italic>MIR129-2<\/jats:italic> methylation was associated with an inferior survival. In MM, <jats:italic>MIR129-2<\/jats:italic> methylation might be acquired during progression from MGUS to symptomatic MM. In NHL, <jats:italic>MIR129-2<\/jats:italic> methylation might collaborate with <jats:italic>MIR124-1<\/jats:italic> and <jats:italic>MIR203<\/jats:italic> methylation in lymphomagenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1756-8722-6-16","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T03:14:11Z","timestamp":1360811651000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Epigenetic inactivation of the MIR129-2 in hematological malignancies"],"prefix":"10.1186","volume":"6","author":[{"given":"Kwan-Yeung","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita Lok-Hay","family":"Yim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yok-Lam","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ying","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pak-Kwan","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Yan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chor-Sang","family":"Chim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,2,14]]},"reference":[{"key":"285_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/hon.694","volume":"20","author":"CS Chim","year":"2002","unstructured":"Chim CS, Liang R, Kwong YL: Hypermethylation of gene promoters in hematological neoplasia. 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