Uncovering growth-Suppressive micro rNAs in lung cancer

X. Liu, L. F. Sempere, F. Galimberti, S. J. Freemantle, C. Black, K. H. Dragnev, M. Yan, S. Fiering, V. Memoli, H. Li, J. Direnzo, Murray Korc, C. N. Cole, M. Bak, S. Kauppinen, E. Dmitrovsky

Research output: Contribution to journalArticle

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Abstract

Purpose: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth- suppressive miRNAs in lung cancer. Experimental Design: miRNA arrays were done on normal lung tissues and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each transgenic line (designated as ED-1 and ED-2 cells, respectively). Each highlighted miRNA was independently transfected into these cells, Growth-suppressive mechanisms were explored. Expression of a computationally predicted miRNA target was examined. These miRNAs were studied in a paired normal-malignant human lung tissue bank. Results: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung tissues. Individual overexpression of miR-34c, miR-145, and miR-142-5p in ED-1 and ED-2 cells markedly repressed cell growth. Anti-mi R cotransfections antagonized this inhibition. The miR-34c target, cyclin E, was repressed by miR-34c transfection and provided a mechanism for observed growth suppression. Conclusions: miR-34c, miR-145, and miR-142-5p were repressed in murine and human lung cancers. Transfection of each miRNA significantly repressed lung cancer cell growth. Thus, these miRNAs were growth suppressive and are proposed to exert antineoplastic effects in the lung.

Original languageEnglish (US)
Pages (from-to)1177-1183
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number4
DOIs
StatePublished - Feb 15 2009
Externally publishedYes

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MicroRNAs
Lung Neoplasms
Growth
Cyclin E
Lung
Reverse Transcription
In Situ Hybridization
Transfection
Tissue Banks
Polymerase Chain Reaction
Proteasome Endopeptidase Complex
Antineoplastic Agents
Transgenic Mice
Research Design
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Liu, X., Sempere, L. F., Galimberti, F., Freemantle, S. J., Black, C., Dragnev, K. H., ... Dmitrovsky, E. (2009). Uncovering growth-Suppressive micro rNAs in lung cancer. Clinical Cancer Research, 15(4), 1177-1183. https://doi.org/10.1158/1078-0432.CCR-08-1355

Uncovering growth-Suppressive micro rNAs in lung cancer. / Liu, X.; Sempere, L. F.; Galimberti, F.; Freemantle, S. J.; Black, C.; Dragnev, K. H.; Yan, M.; Fiering, S.; Memoli, V.; Li, H.; Direnzo, J.; Korc, Murray; Cole, C. N.; Bak, M.; Kauppinen, S.; Dmitrovsky, E.

In: Clinical Cancer Research, Vol. 15, No. 4, 15.02.2009, p. 1177-1183.

Research output: Contribution to journalArticle

Liu, X, Sempere, LF, Galimberti, F, Freemantle, SJ, Black, C, Dragnev, KH, Yan, M, Fiering, S, Memoli, V, Li, H, Direnzo, J, Korc, M, Cole, CN, Bak, M, Kauppinen, S & Dmitrovsky, E 2009, 'Uncovering growth-Suppressive micro rNAs in lung cancer', Clinical Cancer Research, vol. 15, no. 4, pp. 1177-1183. https://doi.org/10.1158/1078-0432.CCR-08-1355
Liu X, Sempere LF, Galimberti F, Freemantle SJ, Black C, Dragnev KH et al. Uncovering growth-Suppressive micro rNAs in lung cancer. Clinical Cancer Research. 2009 Feb 15;15(4):1177-1183. https://doi.org/10.1158/1078-0432.CCR-08-1355
Liu, X. ; Sempere, L. F. ; Galimberti, F. ; Freemantle, S. J. ; Black, C. ; Dragnev, K. H. ; Yan, M. ; Fiering, S. ; Memoli, V. ; Li, H. ; Direnzo, J. ; Korc, Murray ; Cole, C. N. ; Bak, M. ; Kauppinen, S. ; Dmitrovsky, E. / Uncovering growth-Suppressive micro rNAs in lung cancer. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 4. pp. 1177-1183.
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abstract = "Purpose: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth- suppressive miRNAs in lung cancer. Experimental Design: miRNA arrays were done on normal lung tissues and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each transgenic line (designated as ED-1 and ED-2 cells, respectively). Each highlighted miRNA was independently transfected into these cells, Growth-suppressive mechanisms were explored. Expression of a computationally predicted miRNA target was examined. These miRNAs were studied in a paired normal-malignant human lung tissue bank. Results: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung tissues. Individual overexpression of miR-34c, miR-145, and miR-142-5p in ED-1 and ED-2 cells markedly repressed cell growth. Anti-mi R cotransfections antagonized this inhibition. The miR-34c target, cyclin E, was repressed by miR-34c transfection and provided a mechanism for observed growth suppression. Conclusions: miR-34c, miR-145, and miR-142-5p were repressed in murine and human lung cancers. Transfection of each miRNA significantly repressed lung cancer cell growth. Thus, these miRNAs were growth suppressive and are proposed to exert antineoplastic effects in the lung.",
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AU - Sempere, L. F.

AU - Galimberti, F.

AU - Freemantle, S. J.

AU - Black, C.

AU - Dragnev, K. H.

AU - Yan, M.

AU - Fiering, S.

AU - Memoli, V.

AU - Li, H.

AU - Direnzo, J.

AU - Korc, Murray

AU - Cole, C. N.

AU - Bak, M.

AU - Kauppinen, S.

AU - Dmitrovsky, E.

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N2 - Purpose: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth- suppressive miRNAs in lung cancer. Experimental Design: miRNA arrays were done on normal lung tissues and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each transgenic line (designated as ED-1 and ED-2 cells, respectively). Each highlighted miRNA was independently transfected into these cells, Growth-suppressive mechanisms were explored. Expression of a computationally predicted miRNA target was examined. These miRNAs were studied in a paired normal-malignant human lung tissue bank. Results: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung tissues. Individual overexpression of miR-34c, miR-145, and miR-142-5p in ED-1 and ED-2 cells markedly repressed cell growth. Anti-mi R cotransfections antagonized this inhibition. The miR-34c target, cyclin E, was repressed by miR-34c transfection and provided a mechanism for observed growth suppression. Conclusions: miR-34c, miR-145, and miR-142-5p were repressed in murine and human lung cancers. Transfection of each miRNA significantly repressed lung cancer cell growth. Thus, these miRNAs were growth suppressive and are proposed to exert antineoplastic effects in the lung.

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