miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1

Liqin Du, Jeoffrey J. Schageman, Maria C. Subauste, Barbara Saber, Scott M. Hammond, Ludmila Prudkin, Ignacio I. Wistuba, Lin Ji, Jack A. Roth, John D. Minna, Alexander Pertsemlidis

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

FUS1 is a tumor suppressor gene located on human chromosome 3p21, and expression of Fus1 protein is highly regulated at various levels, leading to lost or greatly diminished tumor suppressor function in many lung cancers. Here we show that selected microRNAs (miRNA) interact with the 3′-untranslated region (3′UTR) of FUS1, leading to down-regulation of protein expression. Using computational methods, we first predicted that FUS1 is a target of three miRNAs, miR-93, miR-98, and miR-197, and then showed that exogenous overexpression of these miRNAs inhibited Fus1 protein expression. We then confirmed that the three miRNAs target the 3′UTR region of the FUS1 transcript and that individual deletion of the three miRNA target sites in the FUS1 3′UTR restores the expression level of Fus1 protein. We further found that miR-93 and miR-98 are expressed at higher levels in small-cell lung cancer cell lines (SCLC) than in non-small-cell lung cancer cell lines (NSCLC) and immortalized human bronchial epithelial cells (HBEC), and that miR-197 is expressed at higher levels in both SCLCs and NSCLCs than in HBECs. Finally, we found that elevated miR-93 and miR-197 expression is correlated with reduced Fus1 expression in NSCLC tumor specimens. These results suggest that the three miRNAs are negative regulators of Fus1 expression in lung cancers.

Original languageEnglish (US)
Pages (from-to)1234-1243
Number of pages10
JournalMolecular Cancer Research
Volume7
Issue number8
DOIs
StatePublished - Aug 2009

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Tumor Suppressor Genes
MicroRNAs
3' Untranslated Regions
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Proteins
Cell Line
Small Cell Lung Carcinoma
Human Chromosomes
Tumor Cell Line
Down-Regulation
Epithelial Cells
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Du, L., Schageman, J. J., Subauste, M. C., Saber, B., Hammond, S. M., Prudkin, L., ... Pertsemlidis, A. (2009). miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Molecular Cancer Research, 7(8), 1234-1243. https://doi.org/10.1158/1541-7786.MCR-08-0507

miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. / Du, Liqin; Schageman, Jeoffrey J.; Subauste, Maria C.; Saber, Barbara; Hammond, Scott M.; Prudkin, Ludmila; Wistuba, Ignacio I.; Ji, Lin; Roth, Jack A.; Minna, John D.; Pertsemlidis, Alexander.

In: Molecular Cancer Research, Vol. 7, No. 8, 08.2009, p. 1234-1243.

Research output: Contribution to journalArticle

Du, L, Schageman, JJ, Subauste, MC, Saber, B, Hammond, SM, Prudkin, L, Wistuba, II, Ji, L, Roth, JA, Minna, JD & Pertsemlidis, A 2009, 'miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1', Molecular Cancer Research, vol. 7, no. 8, pp. 1234-1243. https://doi.org/10.1158/1541-7786.MCR-08-0507
Du L, Schageman JJ, Subauste MC, Saber B, Hammond SM, Prudkin L et al. miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Molecular Cancer Research. 2009 Aug;7(8):1234-1243. https://doi.org/10.1158/1541-7786.MCR-08-0507
Du, Liqin ; Schageman, Jeoffrey J. ; Subauste, Maria C. ; Saber, Barbara ; Hammond, Scott M. ; Prudkin, Ludmila ; Wistuba, Ignacio I. ; Ji, Lin ; Roth, Jack A. ; Minna, John D. ; Pertsemlidis, Alexander. / miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. In: Molecular Cancer Research. 2009 ; Vol. 7, No. 8. pp. 1234-1243.
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AU - Hammond, Scott M.

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