The tumor suppressor microRNA let-7 represses the HMGA2 oncogene

Sun Lee Yong, Anindya Dutta

Research output: Contribution to journalArticle

894 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1025-1030
Number of pages6
JournalGenes and Development
Volume21
Issue number9
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

MicroRNAs
Oncogenes
Lung Neoplasms
Neoplasms
High Mobility Group Proteins
Genetic Translocation
3' Untranslated Regions
HeLa Cells
Open Reading Frames
Cytoplasm
Cell Proliferation
Messenger RNA
Growth
Genes

Keywords

  • HMGA2
  • Let-7
  • Lung cancer
  • MicroRNA

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. / Yong, Sun Lee; Dutta, Anindya.

In: Genes and Development, Vol. 21, No. 9, 01.05.2007, p. 1025-1030.

Research output: Contribution to journalArticle

Yong, Sun Lee ; Dutta, Anindya. / The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. In: Genes and Development. 2007 ; Vol. 21, No. 9. pp. 1025-1030.
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