TY - JOUR
T1 - Two-tiered approach identifies a network of cancer and liver disease-related genes regulated by miR-122
AU - Boutz, Daniel R.
AU - Collins, Patrick J.
AU - Suresh, Uthra
AU - Lu, Mingzhu
AU - Ramírez, Cristina M.
AU - Fernández-Hernando, Carlos
AU - Huang, Yufei
AU - Abreu, Raquel De Sousa
AU - Le, Shu Yun
AU - Shapiro, Bruce A.
AU - Liu, Angela M.
AU - Luk, John M.
AU - Aldred, Shelley Force
AU - Trinklein, Nathan D.
AU - Marcotte, Edward M.
AU - Penalva, Luiz O.F.
PY - 2011/5/20
Y1 - 2011/5/20
N2 - MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function.
AB - MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function.
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U2 - 10.1074/jbc.M110.196451
DO - 10.1074/jbc.M110.196451
M3 - Article
C2 - 21402708
AN - SCOPUS:79955975777
VL - 286
SP - 18066
EP - 18078
JO - The Journal of biological chemistry
JF - The Journal of biological chemistry
SN - 0021-9258
IS - 20
ER -