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Cited by 470

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer

Open access
Kim, Young-Kook, Yu, Jieun, Han, Tae Su, Park, Seong-Yeon, Namkoong, Bumjin, Kim, Dong Hyuk, Hur, Keun, Yoo, Moon-Won, Lee, Hyuk-Joon, Yang, Han-Kwang, Kim, V. Narry·2009·Nucleic Acids Research

Abstract

microRNAs (miRNAs) play integral roles in diverse processes including tumorigenesis. miRNA gene loci are often found in close conjunction, and such clustered miRNA genes are transcribed from a common promoter to generate polycistronic primary transcript. The primary transcript (pri-miRNA) is then processed by two RNase III proteins to release the mature miRNAs. Although it has been speculated that the miRNAs in the same cluster may play related biological functions, this has not been experimentally addressed. Here we report that the miRNAs in two clusters (miR-106b approximately 93 approximately 25 and miR-222 approximately 221) suppress the Cip/Kip family members of Cdk inhibitors (p57(Kip2), p21(Cip1) and p27(Kip1)). We show that miR-25 targets p57 through the 3'-UTR. Furthermore, miR-106b and miR-93 control p21 while miR-222 and miR-221 regulate both p27 and p57. Ectopic expression of these miRNAs results in activation of Cdk2 and facilitation of G1/S phase transition. Consistent with these results, both clusters are abnormally upregulated in gastric cancer tissues compared to the corresponding normal tissues. Ectopic expression of miR-222 cluster enhanced tumor growth in the mouse xenograft model. Our study demonstrates the functional associations between clustered miRNAs and further implicates that effective cancer treatment may require a combinatorial approach to target multiple oncogenic miRNA clusters.

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Metadata

Authors
Kim, Y.-K., Yu, J., Han, T. S., Park, S.-Y., Namkoong, B., Kim, D. H., Hur, K., Yoo, M.-W., Lee, H.-J., Yang, H.-K., & Kim, V. N.
Venue
Nucleic Acids Research
Published
2009-01-19
Volume
37
Issue
5
Pages
1672-1681
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2107268184
Cited by
470
References
32
FWCI
13.89
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. https://app.cochat.ai/papers/10.1093/nar/gkp002
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Kim, Y.-K., Yu, J., Han, T. S., Park, S.-Y., Namkoong, B., Kim, D. H., Hur, K., Yoo, M.-W., Lee, H.-J., Yang, H.-K., & Kim, V. N. (2009). Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Research. https://doi.org/10.1093/nar/gkp002

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