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[Cancer Research 65, 6029-6033, July 15, 2005]
© 2005 American Association for Cancer Research

Priority Reports

MicroRNA-21 Is an Antiapoptotic Factor in Human Glioblastoma Cells

Jennifer A. Chan1,3, Anna M. Krichevsky2 and Kenneth S. Kosik4

Departments of 1 Pathology and 2 Neurology, Brigham and Women's Hospital and 3 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; and 4 Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California

Requests for reprints: Anna M. Krichevsky, Neurology, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle HIM 760, Boston, MA 02115. Phone: 617-525-5195; Fax: 617-525-5305; E-mail: krichevsky{at}cnd.bwh.harvard.edu.

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by targeting the mRNA of protein-coding genes for either cleavage or repression of translation. The roles of miRNAs in lineage determination and proliferation as well as the location of several miRNA genes at sites of translocation breakpoints or deletions has led to the speculation that miRNAs could be important factors in the development or maintenance of the neoplastic state. Here we show that the highly malignant human brain tumor, glioblastoma, strongly overexpresses a specific miRNA, miR-21. Our studies show markedly elevated miR-21 levels in human glioblastoma tumor tissues, early-passage glioblastoma cultures, and in six established glioblastoma cell lines (A172, U87, U373, LN229, LN428, and LN308) compared with nonneoplastic fetal and adult brain tissues and compared with cultured nonneoplastic glial cells. Knockdown of miR-21 in cultured glioblastoma cells triggers activation of caspases and leads to increased apoptotic cell death. Our data suggest that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes.




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L. B. Frankel, N. R. Christoffersen, A. Jacobsen, M. Lindow, A. Krogh, and A. H. Lund
Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells
J. Biol. Chem., January 11, 2008; 283(2): 1026 - 1033.
[Abstract] [Full Text] [PDF]

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 Molecular Cancer TherapeuticsHome page
P. E. Blower, J.-H. Chung, J. S. Verducci, S. Lin, J.-K. Park, Z. Dai, C.-G. Liu, T. D. Schmittgen, W. C. Reinhold, C. M. Croce, et al.
MicroRNAs modulate the chemosensitivity of tumor cells
Mol. Cancer Ther., January 1, 2008; 7(1): 1 - 9.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
D. Y. Lee, Z. Deng, C.-H. Wang, and B. B. Yang
MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression
PNAS, December 18, 2007; 104(51): 20350 - 20355.
[Abstract] [Full Text] [PDF]

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 Mol Hum ReprodHome page
Q. Pan, X. Luo, T. Toloubeydokhti, and N. Chegini
The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression
Mol. Hum. Reprod., November 1, 2007; 13(11): 797 - 806.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
J. S. Satterlee, S. Barbee, P. Jin, A. Krichevsky, S. Salama, G. Schratt, and D.-Y. Wu
Noncoding RNAs in the Brain
J. Neurosci., October 31, 2007; 27(44): 11856 - 11859.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. F. Corsten, R. Miranda, R. Kasmieh, A. M. Krichevsky, R. Weissleder, and K. Shah
MicroRNA-21 Knockdown Disrupts Glioma Growth In vivo and Displays Synergistic Cytotoxicity with Neural Precursor Cell Delivered S-TRAIL in Human Gliomas
Cancer Res., October 1, 2007; 67(19): 8994 - 9000.
[Abstract] [Full Text] [PDF]

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 RNAHome page
Y. Xi, G. Nakajima, E. Gavin, C. G. Morris, K. Kudo, K. Hayashi, and J. Ju
Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples
RNA, October 1, 2007; 13(10): 1668 - 1674.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. V. Iorio, R. Visone, G. Di Leva, V. Donati, F. Petrocca, P. Casalini, C. Taccioli, S. Volinia, C.-G. Liu, H. Alder, et al.
MicroRNA Signatures in Human Ovarian Cancer
Cancer Res., September 15, 2007; 67(18): 8699 - 8707.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
W. Zhang, J. E. Dahlberg, and W. Tam
MicroRNAs in Tumorigenesis: A Primer
Am. J. Pathol., September 1, 2007; 171(3): 728 - 738.
[Abstract] [Full Text] [PDF]

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 BloodHome page
D. Loffler, K. Brocke-Heidrich, G. Pfeifer, C. Stocsits, J. Hackermuller, A. K. Kretzschmar, R. Burger, M. Gramatzki, C. Blumert, K. Bauer, et al.
Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer
Blood, August 15, 2007; 110(4): 1330 - 1333.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. Galardi, N. Mercatelli, E. Giorda, S. Massalini, G. V. Frajese, S. A. Ciafre, and M. G. Farace
miR-221 and miR-222 Expression Affects the Proliferation Potential of Human Prostate Carcinoma Cell Lines by Targeting p27Kip1
J. Biol. Chem., August 10, 2007; 282(32): 23716 - 23724.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
P. Sathyan, H. B. Golden, and R. C. Miranda
Competing Interactions between Micro-RNAs Determine Neural Progenitor Survival and Proliferation after Ethanol Exposure: Evidence from an Ex Vivo Model of the Fetal Cerebral Cortical Neuroepithelium
J. Neurosci., August 8, 2007; 27(32): 8546 - 8557.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
T. Thum, P. Galuppo, C. Wolf, J. Fiedler, S. Kneitz, L. W. van Laake, P. A. Doevendans, C. L. Mummery, J. Borlak, A. Haverich, et al.
MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming in Heart Failure
Circulation, July 17, 2007; 116(3): 258 - 267.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
M. F. Mehler and J. S. Mattick
Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease
Physiol Rev, July 1, 2007; 87(3): 799 - 823.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
W.-O. Lui, N. Pourmand, B. K. Patterson, and A. Fire
Patterns of Known and Novel Small RNAs in Human Cervical Cancer
Cancer Res., July 1, 2007; 67(13): 6031 - 6043.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
K. P. Porkka, M. J. Pfeiffer, K. K. Waltering, R. L. Vessella, T. L.J. Tammela, and T. Visakorpi
MicroRNA Expression Profiling in Prostate Cancer
Cancer Res., July 1, 2007; 67(13): 6130 - 6135.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
R. Ji, Y. Cheng, J. Yue, J. Yang, X. Liu, H. Chen, D. B. Dean, and C. Zhang
MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation
Circ. Res., June 8, 2007; 100(11): 1579 - 1588.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. Slape, H. Hartung, Y.-W. Lin, J. Bies, L. Wolff, and P. D. Aplan
Retroviral Insertional Mutagenesis Identifies Genes that Collaborate with NUP98-HOXD13 during Leukemic Transformation
Cancer Res., June 1, 2007; 67(11): 5148 - 5155.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
M. Negrini, M. Ferracin, S. Sabbioni, and C. M. Croce
MicroRNAs in human cancer: from research to therapy
J. Cell Sci., June 1, 2007; 120(11): 1833 - 1840.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
Y. Cheng, R. Ji, J. Yue, J. Yang, X. Liu, H. Chen, D. B. Dean, and C. Zhang
MicroRNAs Are Aberrantly Expressed in Hypertrophic Heart: Do They Play a Role in Cardiac Hypertrophy?
Am. J. Pathol., June 1, 2007; 170(6): 1831 - 1840.
[Abstract] [Full Text] [PDF]

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 BloodHome page
V. Fulci, S. Chiaretti, M. Goldoni, G. Azzalin, N. Carucci, S. Tavolaro, L. Castellano, A. Magrelli, F. Citarella, M. Messina, et al.
Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia
Blood, June 1, 2007; 109(11): 4944 - 4951.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. Zhu, M.-L. Si, H. Wu, and Y.-Y. Mo
MicroRNA-21 Targets the Tumor Suppressor Gene Tropomyosin 1 (TPM1)
J. Biol. Chem., May 11, 2007; 282(19): 14328 - 14336.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
M. Bloomston, W. L. Frankel, F. Petrocca, S. Volinia, H. Alder, J. P. Hagan, C.-G. Liu, D. Bhatt, C. Taccioli, and C. M. Croce
MicroRNA Expression Patterns to Differentiate Pancreatic Adenocarcinoma From Normal Pancreas and Chronic Pancreatitis
JAMA, May 2, 2007; 297(17): 1901 - 1908.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
F. Meng, R. Henson, H. Wehbe-Janek, H. Smith, Y. Ueno, and T. Patel
The MicroRNA let-7a Modulates Interleukin-6-dependent STAT-3 Survival Signaling in Malignant Human Cholangiocytes
J. Biol. Chem., March 16, 2007; 282(11): 8256 - 8264.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
A. Gaur, D. A. Jewell, Y. Liang, D. Ridzon, J. H. Moore, C. Chen, V. R. Ambros, and M. A. Israel
Characterization of MicroRNA Expression Levels and Their Biological Correlates in Human Cancer Cell Lines
Cancer Res., March 15, 2007; 67(6): 2456 - 2468.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
L. L. Coutinho, L. K. Matukumalli, T. S. Sonstegard, C. P. Van Tassell, L. C. Gasbarre, A. V. Capuco, and T. P. L. Smith
Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues
Physiol Genomics, March 14, 2007; 29(1): 35 - 43.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
D. Sayed, C. Hong, I.-Y. Chen, J. Lypowy, and M. Abdellatif
MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy
Circ. Res., February 16, 2007; 100(3): 416 - 424.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
Y. Chen and R. L. Stallings
Differential Patterns of MicroRNA Expression in Neuroblastoma Are Correlated with Prognosis, Differentiation, and Apoptosis
Cancer Res., February 1, 2007; 67(3): 976 - 983.
[Abstract] [Full Text] [PDF]

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 J. Virol.Home page
D. N. Kim, H.-S. Chae, S. T. Oh, J.-H. Kang, C. H. Park, W. S. Park, K. Takada, J. M. Lee, W.-K. Lee, and S. K. Lee
Expression of Viral MicroRNAs in Epstein-Barr Virus-Associated Gastric Carcinoma
J. Virol., January 15, 2007; 81(2): 1033 - 1036.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
K. V. Prasanth and D. L. Spector
Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum
Genes & Dev., January 1, 2007; 21(1): 11 - 42.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
P. L. Boutz, G. Chawla, P. Stoilov, and D. L. Black
MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development
Genes & Dev., January 1, 2007; 21(1): 71 - 84.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
H. Osada and T. Takahashi
MicroRNAs in biological processes and carcinogenesis
Carcinogenesis, January 1, 2007; 28(1): 2 - 12.
[Abstract] [Full Text] [PDF]


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