Uncovering growth-suppressive MicroRNAs in lung cancer

Xi Liu; Lorenzo F Sempere; Fabrizio Galimberti; Sarah J Freemantle; Candice Black; Konstantin H Dragnev; Yan Ma; Steven Fiering; Vincent Memoli; Hua Li; James DiRenzo; Murray Korc; Charles N Cole; Mads Bak; Sakari Kauppinen; Ethan Dmitrovsky

doi:10.1158/1078-0432.CCR-08-1355

Uncovering growth-suppressive MicroRNAs in lung cancer

Xi Liu, Lorenzo F Sempere, Fabrizio Galimberti, Sarah J Freemantle, Candice Black, Konstantin H Dragnev, Yan Ma, Steven Fiering, Vincent Memoli, Hua Li, James DiRenzo, Murray Korc, Charles N Cole, Mads Bak, Sakari Kauppinen, Ethan Dmitrovsky

Medical Genetics Program

168 Citations (Scopus)

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-miR 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 language	English
Journal	Clinical Cancer Research
Volume	15
Issue number	4
Pages (from-to)	1177-83
Number of pages	6
ISSN	1078-0432
DOIs	https://doi.org/10.1158/1078-0432.CCR-08-1355
Publication status	Published - 2009

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10.1158/1078-0432.CCR-08-1355

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@article{1c9fa15090b811df928f000ea68e967b,

title = "Uncovering growth-suppressive MicroRNAs in lung cancer",

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-miR 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.",

author = "Xi Liu and Sempere, {Lorenzo F} and Fabrizio Galimberti and Freemantle, {Sarah J} and Candice Black and Dragnev, {Konstantin H} and Yan Ma and Steven Fiering and Vincent Memoli and Hua Li and James DiRenzo and Murray Korc and Cole, {Charles N} and Mads Bak and Sakari Kauppinen and Ethan Dmitrovsky",

note = "Keywords: Animals; Cell Line, Tumor; Humans; Lung Neoplasms; Mice; Mice, Transgenic; MicroRNAs; Reverse Transcriptase Polymerase Chain Reaction; Transfection",

year = "2009",

doi = "10.1158/1078-0432.CCR-08-1355",

language = "English",

volume = "15",

pages = "1177--83",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research (A A C R)",

number = "4",

}

TY - JOUR

T1 - Uncovering growth-suppressive MicroRNAs in lung cancer

AU - Liu, Xi

AU - Sempere, Lorenzo F

AU - Galimberti, Fabrizio

AU - Freemantle, Sarah J

AU - Black, Candice

AU - Dragnev, Konstantin H

AU - Ma, Yan

AU - Fiering, Steven

AU - Memoli, Vincent

AU - Li, Hua

AU - DiRenzo, James

AU - Korc, Murray

AU - Cole, Charles N

AU - Bak, Mads

AU - Kauppinen, Sakari

AU - Dmitrovsky, Ethan

N1 - Keywords: Animals; Cell Line, Tumor; Humans; Lung Neoplasms; Mice; Mice, Transgenic; MicroRNAs; Reverse Transcriptase Polymerase Chain Reaction; Transfection

PY - 2009

Y1 - 2009

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-miR 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.

AB - 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-miR 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.

U2 - 10.1158/1078-0432.CCR-08-1355

DO - 10.1158/1078-0432.CCR-08-1355

M3 - Journal article

C2 - 19228723

SN - 1078-0432

VL - 15

SP - 1177

EP - 1183

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 4

ER -

Uncovering growth-suppressive MicroRNAs in lung cancer

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