MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors

Xi Liu; Lorenzo F Sempere; Haoxu Ouyang; Vincent A Memoli; Angeline S Andrew; Yue Luo; Eugene Demidenko; Murray Korc; Wei Shi; Meir Preis; Konstantin H Dragnev; Hua Li; James Direnzo; Mads Bak; Sarah J Freemantle; Sakari Kauppinen; Ethan Dmitrovsky

doi:10.1172/JCI39566

MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors

Xi Liu, Lorenzo F Sempere, Haoxu Ouyang, Vincent A Memoli, Angeline S Andrew, Yue Luo, Eugene Demidenko, Murray Korc, Wei Shi, Meir Preis, Konstantin H Dragnev, Hua Li, James Direnzo, Mads Bak, Sarah J Freemantle, Sakari Kauppinen, Ethan Dmitrovsky

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

369 Citationer (Scopus)

Abstract

Udgivelsesdato: 2010-Apr-1

Originalsprog	Engelsk
Tidsskrift	Journal of Clinical Investigation
Vol/bind	120
Udgave nummer	4
Sider (fra-til)	1298-309
Antal sider	11
ISSN	0021-9738
DOI	https://doi.org/10.1172/JCI39566
Status	Udgivet - 2010

Bibliografisk note

Keywords: Animals; Computational Biology; Humans; Lung Neoplasms; Mice; MicroRNAs; Oligonucleotide Array Sequence Analysis; Protein Phosphatase 2; Protein-Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins

Adgang til dokumentet

10.1172/JCI39566

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Citationsformater

Liu, X., Sempere, L. F., Ouyang, H., Memoli, V. A., Andrew, A. S., Luo, Y., Demidenko, E., Korc, M., Shi, W., Preis, M., Dragnev, K. H., Li, H., Direnzo, J., Bak, M., Freemantle, S. J., Kauppinen, S., & Dmitrovsky, E. (2010). MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. Journal of Clinical Investigation, 120(4), 1298-309. https://doi.org/10.1172/JCI39566

Liu, X, Sempere, LF, Ouyang, H, Memoli, VA, Andrew, AS, Luo, Y, Demidenko, E, Korc, M, Shi, W, Preis, M, Dragnev, KH, Li, H, Direnzo, J, Bak, M, Freemantle, SJ, Kauppinen, S & Dmitrovsky, E 2010, 'MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors', Journal of Clinical Investigation, bind 120, nr. 4, s. 1298-309. https://doi.org/10.1172/JCI39566

@article{04b3ae2090bc11df928f000ea68e967b,

title = "MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors",

abstract = "MicroRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31-mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression.",

author = "Xi Liu and Sempere, {Lorenzo F} and Haoxu Ouyang and Memoli, {Vincent A} and Andrew, {Angeline S} and Yue Luo and Eugene Demidenko and Murray Korc and Wei Shi and Meir Preis and Dragnev, {Konstantin H} and Hua Li and James Direnzo and Mads Bak and Freemantle, {Sarah J} and Sakari Kauppinen and Ethan Dmitrovsky",

note = "Keywords: Animals; Computational Biology; Humans; Lung Neoplasms; Mice; MicroRNAs; Oligonucleotide Array Sequence Analysis; Protein Phosphatase 2; Protein-Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins",

year = "2010",

doi = "10.1172/JCI39566",

language = "English",

volume = "120",

pages = "1298--309",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "4",

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TY - JOUR

T1 - MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors

AU - Liu, Xi

AU - Sempere, Lorenzo F

AU - Ouyang, Haoxu

AU - Memoli, Vincent A

AU - Andrew, Angeline S

AU - Luo, Yue

AU - Demidenko, Eugene

AU - Korc, Murray

AU - Shi, Wei

AU - Preis, Meir

AU - Dragnev, Konstantin H

AU - Li, Hua

AU - Direnzo, James

AU - Bak, Mads

AU - Freemantle, Sarah J

AU - Kauppinen, Sakari

AU - Dmitrovsky, Ethan

N1 - Keywords: Animals; Computational Biology; Humans; Lung Neoplasms; Mice; MicroRNAs; Oligonucleotide Array Sequence Analysis; Protein Phosphatase 2; Protein-Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins

PY - 2010

Y1 - 2010

N2 - MicroRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31-mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression.

AB - MicroRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31-mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression.

U2 - 10.1172/JCI39566

DO - 10.1172/JCI39566

M3 - Journal article

C2 - 20237410

SN - 0021-9738

VL - 120

SP - 1298

EP - 1309

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 4

ER -