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

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


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Base Pairing
  • Case-Control Studies
  • DNA Primers / chemistry
  • DNA Primers / genetics
  • Female
  • Gene Expression Profiling*
  • Genetic Association Studies*
  • Humans
  • Immunoprecipitation
  • Inverted Repeat Sequences / genetics*
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / pathology
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Genetic / genetics*
  • Signal Transduction*


  • DNA Primers
  • MIRN202 microRNA, human
  • MicroRNAs