Expression of MiR-124 Inhibits Growth of Medulloblastoma Cells

Overview

Journal Neuro Oncol

Publisher Oxford University Press

Specialties Neurology
Oncology

Date 2012 Nov 23

PMID 23172372

Citations 38

Authors

Joachim Silber

Rintaro Hashizume

Tristan Felix

Sujatmi Hariono

Mamie Yu

Mitchel S Berger

Jason T Huse

Scott R VandenBerg

C David James

J Graeme Hodgson

Nalin Gupta

Affiliations

Soon will be listed here.

Abstract

Medulloblastoma is the most common malignant brain tumor in children, and a substantial number of patients die as a result of tumor progression. Overexpression of CDK6 is present in approximately one-third of medulloblastomas and is an independent poor prognostic marker for this disease. MicroRNA (miR)-124 inhibits expression of CDK6 and prevents proliferation of glioblastoma and medulloblastoma cells in vitro. We examined the effects of miR-124 overexpression on medulloblastoma cells both in vitro and in vivo and compared cell lines that have low and high CDK6 expression. MiR-124 overexpression inhibits the proliferation of medulloblastoma cells, and this effect is mediated mostly through the action of miR-124 upon CDK6. We further show that induced expression of miR-124 potently inhibits growth of medulloblastoma xenograft tumors in rodents. Further testing of miR-124 will help define the ultimate therapeutic potential of preclinical models of medulloblastoma in conjunction with various delivery strategies for treatment.

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References

Sempere L, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V . Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 2004; 5(3):R13. PMC: 395763. DOI: 10.1186/gb-2004-5-3-r13. View

Jiang Y, Ming L, Montero A, Kimchi E, Nikfarjam M, Staveley-OCarroll K . Optimizing imatinib mesylate treatment in gastrointestinal stromal tumors. Gastrointest Cancer Res. 2009; 2(5):245-50. PMC: 2632557. View

Zeltzer P, Boyett J, Finlay J, Albright A, RORKE L, Milstein J . Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999; 17(3):832-45. DOI: 10.1200/JCO.1999.17.3.832. View

Krichevsky A, King K, Donahue C, Khrapko K, Kosik K . A microRNA array reveals extensive regulation of microRNAs during brain development. RNA. 2003; 9(10):1274-81. PMC: 1370491. DOI: 10.1261/rna.5980303. View

Siomi H, Siomi M . On the road to reading the RNA-interference code. Nature. 2009; 457(7228):396-404. DOI: 10.1038/nature07754. View

Li K, Pang J, Ching A, Wong C, Kong X, Wang Y . miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. Hum Pathol. 2009; 40(9):1234-43. DOI: 10.1016/j.humpath.2009.02.003. View

Lujambio A, Ropero S, Ballestar E, Fraga M, Cerrato C, Setien F . Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 2007; 67(4):1424-9. DOI: 10.1158/0008-5472.CAN-06-4218. View

Sarkaria J, Yang L, Grogan P, Kitange G, Carlson B, Schroeder M . Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Mol Cancer Ther. 2007; 6(3):1167-74. DOI: 10.1158/1535-7163.MCT-06-0691. View

Smirnova L, Grafe A, Seiler A, Schumacher S, Nitsch R, Wulczyn F . Regulation of miRNA expression during neural cell specification. Eur J Neurosci. 2005; 21(6):1469-77. DOI: 10.1111/j.1460-9568.2005.03978.x. View

10.

Hayes M, Drummond D, Hong K, Zheng W, Khorosheva V, Cohen J . Increased target specificity of anti-HER2 genospheres by modification of surface charge and degree of PEGylation. Mol Pharm. 2006; 3(6):726-36. DOI: 10.1021/mp060040v. View

11.

Querbes W, Ge P, Zhang W, Fan Y, Costigan J, Charisse K . Direct CNS delivery of siRNA mediates robust silencing in oligodendrocytes. Oligonucleotides. 2008; 19(1):23-29. DOI: 10.1089/oli.2008.0165. View

12.

Bumcrot D, Manoharan M, Koteliansky V, Sah D . RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol. 2006; 2(12):711-9. PMC: 7097247. DOI: 10.1038/nchembio839. View

13.

Gandellini P, Folini M, Zaffaroni N . Towards the definition of prostate cancer-related microRNAs: where are we now?. Trends Mol Med. 2009; 15(9):381-90. DOI: 10.1016/j.molmed.2009.07.004. View

14.

Krichevsky A, Sonntag K, Isacson O, Kosik K . Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells. 2005; 24(4):857-64. PMC: 2605651. DOI: 10.1634/stemcells.2005-0441. View

15.

Mathupala S, Guthikonda M, Sloan A . RNAi based approaches to the treatment of malignant glioma. Technol Cancer Res Treat. 2006; 5(3):261-9. DOI: 10.1177/153303460600500313. View

16.

Silber J, James C, Hodgson J . microRNAs in gliomas: small regulators of a big problem. Neuromolecular Med. 2009; 11(3):208-22. DOI: 10.1007/s12017-009-8087-9. View

17.

Hayes M, Drummond D, Kirpotin D, Zheng W, Noble C, Park J . Genospheres: self-assembling nucleic acid-lipid nanoparticles suitable for targeted gene delivery. Gene Ther. 2005; 13(7):646-51. DOI: 10.1038/sj.gt.3302699. View

18.

Pierson J, Hostager B, Fan R, Vibhakar R . Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol. 2008; 90(1):1-7. DOI: 10.1007/s11060-008-9624-3. View

19.

Silber J, Lim D, Petritsch C, Persson A, Maunakea A, Yu M . miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 2008; 6:14. PMC: 2443372. DOI: 10.1186/1741-7015-6-14. View

20.

Cheng L, Pastrana E, Tavazoie M, Doetsch F . miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 2009; 12(4):399-408. PMC: 2766245. DOI: 10.1038/nn.2294. View