TY - JOUR
T1 - Identification of direct targets for the miR-17-92 cluster by proteomic analysis
AU - Kanzaki, Hirotaka
AU - Ito, Sachio
AU - Hanafusa, Hiroko
AU - Jitsumori, Yoshimi
AU - Tamaru, Seiji
AU - Shimizu, Kenji
AU - Ouchida, Mamoru
PY - 2011/9/17
Y1 - 2011/9/17
N2 - MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally repress the expression of target genes. Many miRNAs have been implicated in a number of diseases, including cancers. The miR-17-92 miRNA cluster is known as a body of oncogenic miRNAs, and has been shown to be overexpressed in several cancers, including lung cancer. Although the overexpression of miR-17-92 is clearly implicated in the development of lung cancer, only a few direct targets for the miR-17-92 cluster have been identified thus far. In this study, we examined miR-17-92 target profiles in SBC-3 small-cell lung cancer cells using a quantitative proteomic strategy to identify direct targets of the miR-17-92 cluster. By knocking down the expression of endogenous miR-19a, miR-20a and miR-92-1, which are contained in the cluster, 112 up-regulated proteins were detected and also identified as potential targets of these miRNAs. Among these candidate targets, we validated one direct target, RAB14. In conclusion, these findings suggest that proteomic approaches are valuable for identifying direct miRNA targets, and we were able to identify a novel direct target for the miR-92-1 using our proteomic strategy.
AB - MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally repress the expression of target genes. Many miRNAs have been implicated in a number of diseases, including cancers. The miR-17-92 miRNA cluster is known as a body of oncogenic miRNAs, and has been shown to be overexpressed in several cancers, including lung cancer. Although the overexpression of miR-17-92 is clearly implicated in the development of lung cancer, only a few direct targets for the miR-17-92 cluster have been identified thus far. In this study, we examined miR-17-92 target profiles in SBC-3 small-cell lung cancer cells using a quantitative proteomic strategy to identify direct targets of the miR-17-92 cluster. By knocking down the expression of endogenous miR-19a, miR-20a and miR-92-1, which are contained in the cluster, 112 up-regulated proteins were detected and also identified as potential targets of these miRNAs. Among these candidate targets, we validated one direct target, RAB14. In conclusion, these findings suggest that proteomic approaches are valuable for identifying direct miRNA targets, and we were able to identify a novel direct target for the miR-92-1 using our proteomic strategy.
KW - Cell biology
KW - MiRNA
KW - Small-cell lung cancer (SCLC)
KW - Target genes
UR - http://www.scopus.com/inward/record.url?scp=80051819856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051819856&partnerID=8YFLogxK
U2 - 10.1002/pmic.201000501
DO - 10.1002/pmic.201000501
M3 - Article
C2 - 21751348
AN - SCOPUS:80051819856
SN - 1615-9853
VL - 11
SP - 3531
EP - 3539
JO - Proteomics
JF - Proteomics
IS - 17
ER -