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PMID: 17437991 Published · ppublish English Journal Article

The tumor suppressor microRNA let-7 represses the HMGA2 oncogene.

Genes & development ·Vol. 21 ·No. 9 ·2007-05-01 ·Pages 1025-30

Lee YS, Dutta A

Abstract

HMGA2, a high-mobility group protein, is oncogenic in a variety of tumors, including benign mesenchymal tumors and lung cancers. Knockdown of Dicer in HeLa cells revealed that the HMGA2 gene is transcriptionally active, but its mRNA is destabilized in the cytoplasm through the microRNA (miRNA) pathway. HMGA2 was derepressed upon inhibition of let-7 in cells with high levels of the miRNA. Ectopic expression of let-7 reduced HMGA2 and cell proliferation in a lung cancer cell. The effect of let-7 on HMGA2 was dependent on multiple target sites in the 3' untranslated region (UTR), and the growth-suppressive effect of let-7 on lung cancer cells was rescued by overexpression of the HMGA2 ORF without a 3'UTR. Our results provide a novel example of suppression of an oncogene by a tumor-suppressive miRNA and suggest that some tumors activate the oncogene through chromosomal translocations that eliminate the oncogene's 3'UTR with the let-7 target sites.

MeSH Terms
3' Untranslated Regions Base Sequence Cell Line, Tumor Cell Proliferation Gene Expression Regulation, Neoplastic HMGA2 Protein/genetics HeLa Cells Humans Lung Neoplasms/genetics,metabolism,pathology MicroRNAs/genetics,metabolism Oncogenes RNA Stability RNA, Messenger/genetics,metabolism RNA, Neoplasm/genetics,metabolism Ribonuclease III/genetics
Chemicals
3' Untranslated Regions HMGA2 Protein MicroRNAs RNA, Messenger RNA, Neoplasm Ribonuclease III
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lee Yong Sun
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA.
Dutta Anindya
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1540407
Published
2007-05-01
Epub
2007-00-16
Pages
1025-30
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1855228
Subset
IM
Grants
NCI NIH HHS · R01 CA089406 · United States
NCI NIH HHS · R01 CA089406-06 · United States
Corrections
CommentIn
PMID: 17473167
External Links
PubMed source DOI: 10.1101/gad.1540407 PMC Full Text View journal details
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