This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Stallings, R. L. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Stallings, R. L.

Differential Patterns of MicroRNA Expression in Neuroblastoma Are Correlated with Prognosis, Differentiation, and Apoptosis

Children's Cancer Research Institute and Department of Pediatrics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

Requests for reprints: Raymond L. Stallings, Children's Cancer Research Institute and Department of Pediatrics, The University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, Mail Code 7784, San Antonio, TX 78229-3900. Phone: 210-562-9028; Fax: 210-562-9014; E-mail: stallings{at}uthscsa.edu.

Neuroblastoma accounts for 15% of pediatric cancer deaths, and although a few protein-coding genes, such as MYCN, are involved with aggressive pathogenicity, the identification of novel biological targets for therapeutic intervention is still a necessary prerequisite for improving patient survival. Expression profiling of 157 microRNA (miRNA) loci in 35 primary neuroblastoma tumors indicates that 32 loci are differentially expressed in favorable and unfavorable tumor subtypes, indicating a potential role of miRNAs in neuroblastoma pathogenesis. Many of these loci are significantly underexpressed in tumors with MYCN amplification, which have particularly poor prognoses. Interestingly, we found that miRNA expression levels substantially change in a MYCN-amplified cell line following exposure to retinoic acid, a compound which is well known for causing reductions in MYCN expression and for inducing neuroblastoma cell lines to undergo neuronal differentiation. We also show that small interfering RNA inhibition of MYCN by itself causes similar alterations in the expression of miRNA loci. In vitro functional studies of one locus, miR-184, indicate that it plays a significant role in apoptosis. The association of experimentally induced alterations of miRNA expression in neuroblastoma cell lines with differentiation or apoptosis leads us to conclude that these loci play important roles in neuroblastoma pathogenesis. We further suggest that MYCN may mediate a tumorigenic effect, in part, through directly or indirectly regulating the expression of miRNAs that are involved with neural cell differentiation and/or apoptosis, warranting substantial further studies of miRNAs as potential therapeutic targets. [Cancer Res 2007;67(3):976–83]

This article has been cited by other articles:

				N. K. Cervigne, P. P. Reis, J. Machado, B. Sadikovic, G. Bradley, N. N. Galloni, M. Pintilie, I. Jurisica, B. Perez-Ordonez, R. Gilbert, et al. Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma Hum. Mol. Genet., December 15, 2009; 18(24): 4818 - 4829. [Abstract] [Full Text] [PDF]

				C. Evangelisti, M. C. Florian, I. Massimi, C. Dominici, G. Giannini, S. Galardi, M. C. Bue, S. Massalini, H. P. McDowell, E. Messi, et al. MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness FASEB J, December 1, 2009; 23(12): 4276 - 4287. [Abstract] [Full Text] [PDF]

				H. Yang, J. Gu, K. K. Wang, W. Zhang, J. Xing, Z. Chen, J. A. Ajani, and X. Wu MicroRNA Expression Signatures in Barrett's Esophagus and Esophageal Adenocarcinoma Clin. Cancer Res., September 15, 2009; 15(18): 5744 - 5752. [Abstract] [Full Text] [PDF]

				Z. Tombol, P. M Szabo, V. Molnar, Z. Wiener, G. Tolgyesi, J. Horanyi, P. Riesz, P. Reismann, A. Patocs, I. Liko, et al. Integrative molecular bioinformatics study of human adrenocortical tumors: microRNA, tissue-specific target prediction, and pathway analysis Endocr. Relat. Cancer, September 1, 2009; 16(3): 895 - 906. [Abstract] [Full Text] [PDF]

				J. S. Wei, P. Johansson, Q.-R. Chen, Y. K. Song, S. Durinck, X. Wen, A. T.C. Cheuk, M. A. Smith, P. Houghton, C. Morton, et al. microRNA Profiling Identifies Cancer-Specific and Prognostic Signatures in Pediatric Malignancies Clin. Cancer Res., September 1, 2009; 15(17): 5560 - 5568. [Abstract] [Full Text] [PDF]

				H. Xu, I. Y. Cheung, H.-F. Guo, and N.-K. V. Cheung MicroRNA miR-29 Modulates Expression of Immunoinhibitory Molecule B7-H3: Potential Implications for Immune Based Therapy of Human Solid Tumors Cancer Res., August 1, 2009; 69(15): 6275 - 6281. [Abstract] [Full Text] [PDF]

				K.-W. Chang, C.-J. Liu, T.-H. Chu, H.-W. Cheng, P.-S. Hung, W.-Y. Hu, and S.-C. Lin Association between High miR-211 microRNA Expression and the Poor Prognosis of Oral Carcinoma Journal of Dental Research, November 1, 2008; 87(11): 1063 - 1068. [Abstract] [Full Text] [PDF]

				S. Bilke, Q.-R. Chen, J. S. Wei, and J. Khan Whole Chromosome Alterations Predict Survival in High-Risk Neuroblastoma without MYCN Amplification Clin. Cancer Res., September 1, 2008; 14(17): 5540 - 5547. [Abstract] [Full Text] [PDF]

				T. Schepeler, J. T. Reinert, M. S. Ostenfeld, L. L. Christensen, A. N. Silahtaroglu, L. Dyrskjot, C. Wiuf, F. J. Sorensen, M. Kruhoffer, S. Laurberg, et al. Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer Cancer Res., August 1, 2008; 68(15): 6416 - 6424. [Abstract] [Full Text] [PDF]

				K.-i. Kozaki, I. Imoto, S. Mogi, K. Omura, and J. Inazawa Exploration of Tumor-Suppressive MicroRNAs Silenced by DNA Hypermethylation in Oral Cancer Cancer Res., April 1, 2008; 68(7): 2094 - 2105. [Abstract] [Full Text] [PDF]

				A. J. Schetter, S. Y. Leung, J. J. Sohn, K. A. Zanetti, E. D. Bowman, N. Yanaihara, S. T. Yuen, T. L. Chan, D. L. W. Kwong, G. K. H. Au, et al. MicroRNA Expression Profiles Associated With Prognosis and Therapeutic Outcome in Colon Adenocarcinoma JAMA, January 30, 2008; 299(4): 425 - 436. [Abstract] [Full Text] [PDF]

				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]

				C. Blenkiron and E. A. Miska miRNAs in cancer: approaches, aetiology, diagnostics and therapy Hum. Mol. Genet., April 15, 2007; 16(R1): R106 - R113. [Abstract] [Full Text] [PDF]