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

Cancer Epidemiol Biomarkers Prev, 2013/3;22(3):327-36.

Hoffman AE[1], Liu R, Fu A, Zheng T, Slack F, Zhu Y

Affiliations

PMID: 23334589DOI: 10.1158/1055-9965.EPI-12-1131-T

Impact factor: 4.09

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.
MeSH terms
Aged; Base Pairing; Case-Control Studies; DNA Primers; Female; Gene Expression Profiling; Genetic Association Studies; Humans; Immunoprecipitation; Inverted Repeat Sequences; Lymphoma, Non-Hodgkin; MicroRNAs; Oligonucleotide Array Sequence Analysis; Polymorphism, Genetic; Signal Transduction
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