Jan 22, 2013

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

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Aaron E HoffmanYong Zhu


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

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Mentioned in this Paper

Biochemical Pathway
Tumor Suppressor Genes
Lymphoma, Non-Hodgkin
Stem-Loop Sequence
Germ-Line Mutation
Ribonucleoprotein Activity
Hairpin Loop Sequence
RNA, Small Temporal
Genetic Association Studies
Candidate Gene Identification

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