DOI: 10.1101/gad.1540407. The tumor suppressor microRNA <i>let-7</i> represses the HMGA2 oncogene

The tumor suppressor microRNA let-7 represses the HMGA2 oncogene

10.1101/gad.1540407

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

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.

Bibliography

Lee, Y. S., & Dutta, A. (2007). The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes & Development, 21(9), 1025â1030.

Authors 2

Yong Sun Lee (first)
Anindya Dutta (additional)

References 35 Referenced 954

10.1016/S0165-4608(03)00037-2
10.1038/sj.onc.1202881
10.1128/MCB.15.3.1545 / Mol. Cell. Biol. / Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells by Berlingieri, (1995)
10.1038/sj.onc.1201135
10.1016/0165-4608(96)00062-3
10.1038/sj.onc.1204577
10.1073/pnas.0506654102
10.1101/gad.1184404
10.1038/nrm2080
10.1093/carcin/22.10.1583
10.1016/S0165-4608(96)00411-6
10.1016/0014-4827(89)90352-2
10.1186/1476-4598-6-5
10.1126/science.1073827
10.1126/science.1062961
10.1016/j.cell.2004.12.038
10.1016/j.cell.2005.01.014
10.1083/jcb.200603008
{'key': '2021111607533852000_21.9.1025.19', 'first-page': '560', 'article-title': 'MicroRNAs: Small but potent oncogenes or tumor suppressors', 'volume': '7', 'author': 'Lee,', 'year': '2006', 'journal-title': 'Curr. Opin. Investig. Drugs'} / Curr. Opin. Investig. Drugs / MicroRNAs: Small but potent oncogenes or tumor suppressors by Lee, (2006)
10.1038/nature01957
10.1074/jbc.M412247200
10.1126/science.1137999
10.1007/s00428-005-0037-9
10.1038/sj.leu.2403605
{'key': '2021111607533852000_21.9.1025.25', 'first-page': '1351', 'article-title': 'Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15', 'volume': '63', 'author': 'Quade,', 'year': '2003', 'journal-title': 'Cancer Res.'} / Cancer Res. / Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15 by Quade, (2003)
10.1016/S0378-1119(01)00689-8
10.1038/35002607
{'key': '2021111607533852000_21.9.1025.28', 'first-page': '775', 'article-title': 'HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors', 'volume': '149', 'author': 'Rogalla,', 'year': '1996', 'journal-title': 'Am. J. Pathol.'} / Am. J. Pathol. / HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors by Rogalla, (1996)
10.1002/path.1960
10.1038/ng0895-436
10.1186/1471-2105-5-139
10.1158/0008-5472.CAN-04-0637
10.1002/gcc.20415
10.1158/0008-5472.CAN-06-0931
10.1038/376771a0

Dates

Type	When
Created	18 years, 4 months ago (April 16, 2007, 8:24 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 12:05 p.m.)
Indexed	3 days, 5 hours ago (Sept. 3, 2025, 6:17 a.m.)
Issued	18 years, 4 months ago (April 16, 2007)
Published	18 years, 4 months ago (April 16, 2007)
Published Online	18 years, 4 months ago (April 16, 2007)
Published Print	18 years, 4 months ago (May 1, 2007)

Funders 0

None

BibTeX

@article{Lee_2007, title={The tumor suppressor microRNA let-7 represses the HMGA2 oncogene}, volume={21}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1540407}, DOI={10.1101/gad.1540407}, number={9}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Lee, Yong Sun and Dutta, Anindya}, year={2007}, month=apr, pages={1025–1030} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        3
      ]
    ],
    "date-time": "2025-09-03T10:17:28Z",
    "timestamp": 1756894648621
  },
  "reference-count": 35,
  "publisher": "Cold Spring Harbor Laboratory",
  "issue": "9",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2007,
        5,
        1
      ]
    ]
  },
  "abstract": "<jats:p>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 <jats:italic>let-7</jats:italic> in cells with high levels of the miRNA. Ectopic expression of <jats:italic>let-7</jats:italic> reduced HMGA2 and cell proliferation in a lung cancer cell. The effect of <jats:italic>let-7</jats:italic> on HMGA2 was dependent on multiple target sites in the 3\u2032 untranslated region (UTR), and the growth-suppressive effect of <jats:italic>let-7</jats:italic> on lung cancer cells was rescued by overexpression of the HMGA2 ORF without a 3\u2032UTR. 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\u2019s 3\u2032UTR with the <jats:italic>let-7</jats:italic> target sites.</jats:p>",
  "DOI": "10.1101/gad.1540407",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2007,
        4,
        17
      ]
    ],
    "date-time": "2007-04-17T00:24:42Z",
    "timestamp": 1176769482000
  },
  "page": "1025-1030",
  "source": "Crossref",
  "is-referenced-by-count": 954,
  "title": "The tumor suppressor microRNA <i>let-7</i> represses the HMGA2 oncogene",
  "prefix": "10.1101",
  "volume": "21",
  "author": [
    {
      "given": "Yong Sun",
      "family": "Lee",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Anindya",
      "family": "Dutta",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "246",
  "published-online": {
    "date-parts": [
      [
        2007,
        4,
        16
      ]
    ]
  },
  "reference": [
    {
      "key": "2021111607533852000_21.9.1025.1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0165-4608(03)00037-2"
    },
    {
      "key": "2021111607533852000_21.9.1025.2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.onc.1202881"
    },
    {
      "key": "2021111607533852000_21.9.1025.3",
      "doi-asserted-by": "crossref",
      "first-page": "1545",
      "DOI": "10.1128/MCB.15.3.1545",
      "article-title": "Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells",
      "volume": "15",
      "author": "Berlingieri,",
      "year": "1995",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2021111607533852000_21.9.1025.4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.onc.1201135"
    },
    {
      "key": "2021111607533852000_21.9.1025.5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0165-4608(96)00062-3"
    },
    {
      "key": "2021111607533852000_21.9.1025.6",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.onc.1204577"
    },
    {
      "key": "2021111607533852000_21.9.1025.7",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0506654102"
    },
    {
      "key": "2021111607533852000_21.9.1025.8",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.1184404"
    },
    {
      "key": "2021111607533852000_21.9.1025.9",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrm2080"
    },
    {
      "key": "2021111607533852000_21.9.1025.10",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/carcin/22.10.1583"
    },
    {
      "key": "2021111607533852000_21.9.1025.11",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0165-4608(96)00411-6"
    },
    {
      "key": "2021111607533852000_21.9.1025.12",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-4827(89)90352-2"
    },
    {
      "key": "2021111607533852000_21.9.1025.13",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/1476-4598-6-5"
    },
    {
      "key": "2021111607533852000_21.9.1025.14",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1073827"
    },
    {
      "key": "2021111607533852000_21.9.1025.15",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1062961"
    },
    {
      "key": "2021111607533852000_21.9.1025.16",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2004.12.038"
    },
    {
      "key": "2021111607533852000_21.9.1025.17",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2005.01.014"
    },
    {
      "key": "2021111607533852000_21.9.1025.18",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200603008"
    },
    {
      "key": "2021111607533852000_21.9.1025.19",
      "first-page": "560",
      "article-title": "MicroRNAs: Small but potent oncogenes or tumor suppressors",
      "volume": "7",
      "author": "Lee,",
      "year": "2006",
      "journal-title": "Curr. Opin. Investig. Drugs"
    },
    {
      "key": "2021111607533852000_21.9.1025.20",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01957"
    },
    {
      "key": "2021111607533852000_21.9.1025.21",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M412247200"
    },
    {
      "key": "2021111607533852000_21.9.1025.22",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1137999"
    },
    {
      "key": "2021111607533852000_21.9.1025.23",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s00428-005-0037-9"
    },
    {
      "key": "2021111607533852000_21.9.1025.24",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.leu.2403605"
    },
    {
      "key": "2021111607533852000_21.9.1025.25",
      "first-page": "1351",
      "article-title": "Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15",
      "volume": "63",
      "author": "Quade,",
      "year": "2003",
      "journal-title": "Cancer Res."
    },
    {
      "key": "2021111607533852000_21.9.1025.26",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0378-1119(01)00689-8"
    },
    {
      "key": "2021111607533852000_21.9.1025.27",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35002607"
    },
    {
      "key": "2021111607533852000_21.9.1025.28",
      "first-page": "775",
      "article-title": "HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors",
      "volume": "149",
      "author": "Rogalla,",
      "year": "1996",
      "journal-title": "Am. J. Pathol."
    },
    {
      "key": "2021111607533852000_21.9.1025.29",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/path.1960"
    },
    {
      "key": "2021111607533852000_21.9.1025.30",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng0895-436"
    },
    {
      "key": "2021111607533852000_21.9.1025.31",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/1471-2105-5-139"
    },
    {
      "key": "2021111607533852000_21.9.1025.32",
      "doi-asserted-by": "publisher",
      "DOI": "10.1158/0008-5472.CAN-04-0637"
    },
    {
      "key": "2021111607533852000_21.9.1025.33",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/gcc.20415"
    },
    {
      "key": "2021111607533852000_21.9.1025.34",
      "doi-asserted-by": "publisher",
      "DOI": "10.1158/0008-5472.CAN-06-0931"
    },
    {
      "key": "2021111607533852000_21.9.1025.35",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/376771a0"
    }
  ],
  "container-title": "Genes &amp; Development",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://syndication.highwire.org/content/doi/10.1101/gad.1540407",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2021,
        11,
        16
      ]
    ],
    "date-time": "2021-11-16T17:05:32Z",
    "timestamp": 1637082332000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "http://genesdev.cshlp.org/lookup/doi/10.1101/gad.1540407"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2007,
        4,
        16
      ]
    ]
  },
  "references-count": 35,
  "journal-issue": {
    "issue": "9",
    "published-print": {
      "date-parts": [
        [
          2007,
          5,
          1
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1101/gad.1540407"
  ],
  "URL": "http://dx.doi.org/10.1101/gad.1540407",
  "relation": {},
  "ISSN": [
    "0890-9369",
    "1549-5477"
  ],
  "subject": [],
  "container-title-short": "Genes Dev.",
  "published": {
    "date-parts": [
      [
        2007,
        4,
        16
      ]
    ]
  }
}