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Cancer Epidemiol Biomarkers Prev. 2013 Mar;22(3):327-36. doi: 10.1158/1055-9965.EPI-12-1131-T. Epub 2013 Jan 18.

Targetome profiling, pathway analysis and genetic association study implicate miR-202 in lymphomagenesis.

Author information

  • 1Corresponding Author: Yong Zhu, Yale School of Public Health, Yale School of Medicine, New Haven, CT 06520, USA. yong.zhu@yale.edu

Abstract

BACKGROUND:

miRNAs have been implicated in numerous tumorigenic pathways, and previous studies have associated miR-202 dysregulation with various cancer types, including follicular lymphoma.

METHODS:

The miR-202 targetome was identified by ribonucleoprotein immunoprecipitation-microarray (RIP-Chip), and functional interactions among identified targets were investigated using the Ingenuity Pathway Analysis tool. We also conducted a population-based genetic association study of a polymorphism within the miR-202 stem-loop sequence and risk of non-Hodgkin lymphoma. In vitro gain-of-function experiments were further conducted to elucidate the functional significance of the variant.

RESULTS:

A total of 141 potential members of the miR-202 targetome were identified by a transcriptome-wide RIP-Chip assay. Functional interactions among identified targets suggested that miR-202-regulated genes are involved in biologic pathways relevant for hematologic function and cancer. Consistent with this, a genetic association analysis using human blood samples revealed a significant association between a germline mutation (rs12355840) in the miR-202 precursor sequence and follicular lymphoma risk. An in vitro functional assay further showed that the variant allele resulted in diminished miR-202 levels, possibly by altering precursor-processing efficiency.

CONCLUSIONS:

Taken together, our findings suggest that miR-202 is involved in follicular lymphomagenesis.

IMPACT:

These findings implicate miR-202 as a potential tumor suppressor in follicular lymphoma and warrant the investigation of miR-202 as a novel biomarker of follicular lymphoma risk.

PMID:
23334589
[PubMed - indexed for MEDLINE]
PMCID:
PMC3905613
Free PMC Article
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