title: Targetome profiling, pathway analysis and genetic association study implicate miR-202 in lymphomagenesis.
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.
  
  
  CONCLUSIONS
  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.
authors: Corresponding Author: Yong Zhu, Yale School of Public Health, Yale School of Medicine, New Haven, CT 06520, USA. yong.zhu@yale.edu
authors: Aaron E
authors: AE
authors: Hoffman
authors: Ran
authors: R
authors: Liu
authors: Alan
authors: A
authors: Fu
authors: Tongzhang
authors: T
authors: Zheng
authors: Frank
authors: F
authors: Slack
authors: Yong
authors: Y
authors: Zhu
mesh_terms: D000368:Aged; D020029:Base Pairing; D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D047468:Immunoprecipitation; D055029:Inverted Repeat Sequences / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; C569392:MIRN202 microRNA, human; D035683:MicroRNAs