Methylation of <i>miR-155-3p</i> in mantle cell lymphoma and other non-Hodgkin's lymphomas
Bibliographic record
Abstract
// Rita Lh Yim 1 , Kwan Yeung Wong 1 , Yok Lam Kwong 1 , Florence Loong 2 , Chung Ying Leung 3 , Raymond Chu 4 , William Wai Lung Lam 5 , Pak Kwan Hui 6 , Raymond Lai 7 , Chor Sang Chim 1 1 Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong 2 Department of Pathology, Queen Mary Hospital, Hong Kong 3 Department of Pathology, United Christian Hospital, Hong Kong 4 Department of Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong 5 Department of Pathology, Princess Margaret Hospital, Hong Kong 6 Department of Pathology, Kwong Wah Hospital, Hong Kong 7 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada Correspondence to: Chor-Sang Chim, e-mail: jcschim@hku.hk Key Words: tumor suppressive microRNA, hypermethylation, miR-155-3p, mantle cell lymphoma, non-Hodgkin’s lymphoma Received: July 08, 2014 Accepted: August 23, 2014 Published: November 11, 2014 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".