MiR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer

L. Du, Z. Zhao, X. Ma, T. H. Hsiao, Y. Chen, E. Young, M. Suraokar, I. Wistuba, J. D. Minna, A. Pertsemlidis

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor gene with its expression downregulated in multiple cancer types. The role of DAB2 in lung tumorigenesis, however, is not fully characterized, and the mechanisms of DAB2 dysregulation in lung cancer are not defined. Here we show that low DAB2 levels in lung tumor specimens are significantly correlated with poor patient survival, and that DAB2 overexpression significantly inhibits cell growth in cultured lung cancer cells, indicating its potent tumor suppressor function. We next identify that microRNA miR-93 functions as a potent repressor of DAB2 expression by directly targeting the 3′UTR of the DAB2 mRNA. Using in vitro and in vivo approaches, we demonstrate that miR-93 overexpression has an important role in promoting lung cancer cell growth, and that its oncogenic function is primarily mediated by downregulating DAB2 expression. Our clinical investigations further indicate that high tumor levels of miR-93 are correlated with poor survival of lung cancer patients. The correlations of both low DAB2 and high miR-93 expression levels with poor patient survival strongly support the critical role of the miR-93/DAB2 pathway in determining lung cancer progression.

Original languageEnglish (US)
Pages (from-to)4307-4315
Number of pages9
JournalOncogene
Volume33
Issue number34
DOIs
StatePublished - Aug 21 2014

Fingerprint

Lung Neoplasms
Down-Regulation
Survival
Neoplasms
Lung
Growth
Tumor Suppressor Genes
MicroRNAs
Carcinogenesis
Messenger RNA
Genes

Keywords

  • DAB2
  • lung cancer
  • miR-93
  • miRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Du, L., Zhao, Z., Ma, X., Hsiao, T. H., Chen, Y., Young, E., ... Pertsemlidis, A. (2014). MiR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer. Oncogene, 33(34), 4307-4315. https://doi.org/10.1038/onc.2013.381

MiR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer. / Du, L.; Zhao, Z.; Ma, X.; Hsiao, T. H.; Chen, Y.; Young, E.; Suraokar, M.; Wistuba, I.; Minna, J. D.; Pertsemlidis, A.

In: Oncogene, Vol. 33, No. 34, 21.08.2014, p. 4307-4315.

Research output: Contribution to journalArticle

Du, L, Zhao, Z, Ma, X, Hsiao, TH, Chen, Y, Young, E, Suraokar, M, Wistuba, I, Minna, JD & Pertsemlidis, A 2014, 'MiR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer', Oncogene, vol. 33, no. 34, pp. 4307-4315. https://doi.org/10.1038/onc.2013.381
Du, L. ; Zhao, Z. ; Ma, X. ; Hsiao, T. H. ; Chen, Y. ; Young, E. ; Suraokar, M. ; Wistuba, I. ; Minna, J. D. ; Pertsemlidis, A. / MiR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer. In: Oncogene. 2014 ; Vol. 33, No. 34. pp. 4307-4315.
@article{565a00497f6041bcaff2968587ed9368,
title = "MiR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer",
abstract = "The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor gene with its expression downregulated in multiple cancer types. The role of DAB2 in lung tumorigenesis, however, is not fully characterized, and the mechanisms of DAB2 dysregulation in lung cancer are not defined. Here we show that low DAB2 levels in lung tumor specimens are significantly correlated with poor patient survival, and that DAB2 overexpression significantly inhibits cell growth in cultured lung cancer cells, indicating its potent tumor suppressor function. We next identify that microRNA miR-93 functions as a potent repressor of DAB2 expression by directly targeting the 3′UTR of the DAB2 mRNA. Using in vitro and in vivo approaches, we demonstrate that miR-93 overexpression has an important role in promoting lung cancer cell growth, and that its oncogenic function is primarily mediated by downregulating DAB2 expression. Our clinical investigations further indicate that high tumor levels of miR-93 are correlated with poor survival of lung cancer patients. The correlations of both low DAB2 and high miR-93 expression levels with poor patient survival strongly support the critical role of the miR-93/DAB2 pathway in determining lung cancer progression.",
keywords = "DAB2, lung cancer, miR-93, miRNA",
author = "L. Du and Z. Zhao and X. Ma and Hsiao, {T. H.} and Y. Chen and E. Young and M. Suraokar and I. Wistuba and Minna, {J. D.} and A. Pertsemlidis",
year = "2014",
month = "8",
day = "21",
doi = "10.1038/onc.2013.381",
language = "English (US)",
volume = "33",
pages = "4307--4315",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "34",

}

TY - JOUR

T1 - MiR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer

AU - Du, L.

AU - Zhao, Z.

AU - Ma, X.

AU - Hsiao, T. H.

AU - Chen, Y.

AU - Young, E.

AU - Suraokar, M.

AU - Wistuba, I.

AU - Minna, J. D.

AU - Pertsemlidis, A.

PY - 2014/8/21

Y1 - 2014/8/21

N2 - The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor gene with its expression downregulated in multiple cancer types. The role of DAB2 in lung tumorigenesis, however, is not fully characterized, and the mechanisms of DAB2 dysregulation in lung cancer are not defined. Here we show that low DAB2 levels in lung tumor specimens are significantly correlated with poor patient survival, and that DAB2 overexpression significantly inhibits cell growth in cultured lung cancer cells, indicating its potent tumor suppressor function. We next identify that microRNA miR-93 functions as a potent repressor of DAB2 expression by directly targeting the 3′UTR of the DAB2 mRNA. Using in vitro and in vivo approaches, we demonstrate that miR-93 overexpression has an important role in promoting lung cancer cell growth, and that its oncogenic function is primarily mediated by downregulating DAB2 expression. Our clinical investigations further indicate that high tumor levels of miR-93 are correlated with poor survival of lung cancer patients. The correlations of both low DAB2 and high miR-93 expression levels with poor patient survival strongly support the critical role of the miR-93/DAB2 pathway in determining lung cancer progression.

AB - The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor gene with its expression downregulated in multiple cancer types. The role of DAB2 in lung tumorigenesis, however, is not fully characterized, and the mechanisms of DAB2 dysregulation in lung cancer are not defined. Here we show that low DAB2 levels in lung tumor specimens are significantly correlated with poor patient survival, and that DAB2 overexpression significantly inhibits cell growth in cultured lung cancer cells, indicating its potent tumor suppressor function. We next identify that microRNA miR-93 functions as a potent repressor of DAB2 expression by directly targeting the 3′UTR of the DAB2 mRNA. Using in vitro and in vivo approaches, we demonstrate that miR-93 overexpression has an important role in promoting lung cancer cell growth, and that its oncogenic function is primarily mediated by downregulating DAB2 expression. Our clinical investigations further indicate that high tumor levels of miR-93 are correlated with poor survival of lung cancer patients. The correlations of both low DAB2 and high miR-93 expression levels with poor patient survival strongly support the critical role of the miR-93/DAB2 pathway in determining lung cancer progression.

KW - DAB2

KW - lung cancer

KW - miR-93

KW - miRNA

UR - http://www.scopus.com/inward/record.url?scp=84906937334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906937334&partnerID=8YFLogxK

U2 - 10.1038/onc.2013.381

DO - 10.1038/onc.2013.381

M3 - Article

VL - 33

SP - 4307

EP - 4315

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 34

ER -