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American Association for Cancer Research, Cancer Epidemiology, Biomarkers & Prevention, 3(22), p. 327-336, 2013

DOI: 10.1158/1055-9965.epi-12-1131-t

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

Journal article published in 2013 by Aaron E. Hoffman, Ran Liu, Alan Fu, Tongzhang Zheng, Frank J. Slack ORCID, Yong Zhu
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

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. Cancer Epidemiol Biomarkers Prev; 22(3); 327–36. ©2013 AACR.