Targetome Profiling, Pathway Analysis and Genetic Association Study Implicate miR-202 in Lymphomagenesis

被引：35

作者：

Hoffman, Aaron E. ^{[1
,2
]}

Liu, Ran ^{[3
,4
]}

Fu, Alan ^{[4
]}

Zheng, Tongzhang ^{[4
]}

Slack, Frank ^{[5
]}

Zhu, Yong ^{[4
]}

机构：

[1] Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA

[2] Tulane Canc Ctr, New Orleans, LA USA

[3] Southeast Univ, Sch Publ Hlth, Key Lab Environm Med Engn, Nanjing, Jiangsu, Peoples R China

[4] Yale Univ, Sch Med, Sch Publ Hlth, New Haven, CT 06520 USA

[5] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2013年 / 22卷 / 03期

关键词：

B-CELL LYMPHOMA; NON-HODGKIN-LYMPHOMA; PHASE KINASE PROTEIN-2; FOLLICULAR LYMPHOMA; LONG ARM; COLORECTAL-CANCER; BREAST-CANCER; EXPRESSION; MICRORNAS; CHROMOSOME-10;

D O I：

10.1158/1055-9965.EPI-12-1131-T

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C)2013 AACR.

引用

页码：327 / 336

页数：10

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