CoChat
Sign Up
Cited by 765

miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells

Silber, Joachim, Lim, Daniel A, Petritsch, Claudia, Persson, Anders I, Maunakea, Alika K, Yu, Mamie, Vandenberg, Scott R, Ginzinger, David G +6 more·2008·BMC Medicine
DOI 10.1186/1741-7015-6-14PMC PMC2443372
Open this paper in CoChat — free account

Abstract

Background: Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells. Methods: We used quantitative RT-PCR to assess microRNA expression in high-grade astrocytomas and adult mouse neural stem cells. To assess the function of candidate microRNAs in high-grade astrocytomas, we transfected miR mimics to cultured-mouse neural stem cells, -mouse oligodendroglioma-derived stem cells, -human glioblastoma multiforme-derived stem cells and -glioblastoma multiforme cell lines. Cellular differentiation was assessed by immunostaining, and cellular proliferation was determined using fluorescence-activated cell sorting. Results: Our studies revealed that expression levels of microRNA-124 and microRNA-137 were significantly decreased in anaplastic astrocytomas (World Health Organization grade III) and glioblastoma multiforme (World Health Organization grade IV) relative to non-neoplastic brain tissue (P < 0.01), and were increased 8- to 20-fold during differentiation of cultured mouse neural stem cells following growth factor withdrawal. Expression of microRNA-137 was increased 3- to 12-fold in glioblastoma multiforme cell lines U87 and U251 following inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5-aza-dC). Transfection of microRNA-124 or microRNA-137 induced morphological changes and marker expressions consistent with neuronal differentiation in mouse neural stem cells, mouse oligodendroglioma-derived stem cells derived from S100β-v-erbB tumors and cluster of differentiation 133+ human glioblastoma multiforme-derived stem cells (SF6969). Transfection of microRNA-124 or microRNA-137 also induced G1 cell cycle arrest in U251 and SF6969 glioblastoma multiforme cells, which was associated with decreased expression of cyclin-dependent kinase 6 and phosphorylated retinoblastoma (pSer 807/811) proteins. Conclusion: microRNA-124 and microRNA-137 induce differentiation of adult mouse neural stem cells, mouse oligodendroglioma-derived stem cells and human glioblastoma multiforme-derived stem cells and induce glioblastoma multiforme cell cycle arrest. These results suggest that targeted delivery of microRNA-124 and/or microRNA-137 to glioblastoma multiforme tumor cells may be therapeutically efficacious for the treatment of this disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1741-7015-6-14

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 45

  1. Zeng Y Principles of micro-RNA production and maturation Oncogene 2006 25 6156 6162 17028594 10.1038/sj.onc.1209908 · DOI · Paper page
  2. Hatfield SD Shcherbata HR Fischer KA Nakahara K Carthew RW Ruohola-Baker H Stem cell division is regulated by the microRNA pathway Nature 2005 435 974 978 15944714 10.1038/nature03816 · DOI
  3. Murchison EP Partridge JF Tam OH Cheloufi S Hannon GJ Characterization of Dicer-deficient murine embryonic stem cells Proc Natl Acad Sci USA 2005 102 12135 12140 16099834 10.1073/pnas.0505479102 PMC1185572 · DOI · Paper page
  4. Wienholds E Koudijs MJ van Eeden FJ Cuppen E Plasterk RH The microRNA-producing enzyme Dicer1 is essential for zebrafish development Nat Genet 2003 35 217 218 14528306 10.1038/ng1251 · DOI
  5. Bernstein E Kim SY Carmell MA Murchison EP Alcorn H Li MZ Mills AA Elledge SJ Anderson KV Hannon GJ Dicer is essential for mouse development Nat Genet 2003 35 215 217 14528307 10.1038/ng1253 · DOI
  6. Dews M Homayouni A Yu D Murphy D Sevignani C Wentzel E Furth EE Lee WM Enders GH Mendell JT Thomas-Tikhonenko A Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster Nat Genet 2006 38 1060 1065 16878133 10.1038/ng1855 PMC2669546 · DOI
  7. He L Thomson JM Hemann MT Hernando-Monge E Mu D Goodson S Powers S Cordon-Cardo C Lowe SW Hannon GJ Hammond SM A microRNA polycistron as a potential human oncogene Nature 2005 435 828 833 15944707 10.1038/nature03552 PMC4599349 · DOI
  8. Johnson SM Grosshans H Shingara J Byrom M Jarvis R Cheng A Labourier E Reinert KL Brown D Slack FJ RAS is regulated by the let-7 microRNA family Cell 2005 120 635 647 15766527 10.1016/j.cell.2005.01.014 · DOI
  9. Takamizawa J Konishi H Yanagisawa K Tomida S Osada H Endoh H Harano T Yatabe Y Nagino M Nimura Y Mitsudomi T Takahashi T Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival Cancer Res 2004 64 3753 3756 15172979 10.1158/0008-5472.CAN-04-0637 · DOI
  10. Kumar MS Lu J Mercer KL Golub TR Jacks T Impaired microRNA processing enhances cellular transformation and tumorigenesis Nat Genet 2007 39 673 677 17401365 10.1038/ng2003 · DOI
  11. Lu J Getz G Miska EA Alvarez-Saavedra E Lamb J Peck D Sweet-Cordero A Ebert BL Mak RH Ferrando AA Downing JR Jacks T Horvitz HR Golub TR MicroRNA expression profiles classify human cancers Nature 2005 435 834 838 15944708 10.1038/nature03702 · DOI
  12. Krichevsky AM Sonntag KC Isacson O Kosik KS Specific microRNAs modulate embryonic stem cell-derived neurogenesis Stem Cells 2006 24 857 864 16357340 10.1634/stemcells.2005-0441 PMC2605651 · DOI · Paper page
  13. Makeyev EV Zhang J Carrasco MA Maniatis T The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing Mol Cell 2007 27 435 448 17679093 10.1016/j.molcel.2007.07.015 PMC3139456 · DOI · Paper page
  14. Galli R Binda E Orfanelli U Cipelletti B Gritti A De Vitis S Fiocco R Foroni C Dimeco F Vescovi A Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma Cancer Res 2004 64 7011 7021 15466194 10.1158/0008-5472.CAN-04-1364 · DOI
  15. Singh SK Hawkins C Clarke ID Squire JA Bayani J Hide T Henkelman RM Cusimano MD Dirks PB Identification of human brain tumour initiating cells Nature 2004 432 396 401 15549107 10.1038/nature03128 · DOI
  16. Piccirillo SG Reynolds BA Zanetti N Lamorte G Binda E Broggi G Brem H Olivi A Dimeco F Vescovi AL Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells Nature 2006 444 761 765 17151667 10.1038/nature05349 · DOI
  17. Fomchenko EI Holland EC Stem cells and brain cancer Exp Cell Res 2005 306 323 329 15925587 10.1016/j.yexcr.2005.03.007 · DOI
  18. Scheffler B Walton NM Lin DD Goetz AK Enikolopov G Roper SN Steindler DA Phenotypic and functional characterization of adult brain neuropoiesis Proc Natl Acad Sci USA 2005 102 9353 9358 15961540 10.1073/pnas.0503965102 PMC1150897 · DOI
  19. Weiss WA Burns MJ Hackett C Aldape K Hill JR Kuriyama H Kuriyama N Milshteyn N Roberts T Wendland MF DePinho R Israel MA Genetic determinants of malignancy in a mouse model for oligodendroglioma Cancer Res 2003 63 1589 1595 12670909
  20. Chan JA Krichevsky AM Kosik KS MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells Cancer Res 2005 65 6029 6033 16024602 10.1158/0008-5472.CAN-05-0137 · DOI · Paper page
  21. Ciafre SA Galardi S Mangiola A Ferracin M Liu CG Sabatino G Negrini M Maira G Croce CM Farace MG Extensive modulation of a set of microRNAs in primary glioblastoma Biochem Biophys Res Commun 2005 334 1351 1358 16039986 10.1016/j.bbrc.2005.07.030 · DOI · Paper page
  22. Li X Carthew RW A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye Cell 2005 123 1267 1277 16377567 10.1016/j.cell.2005.10.040 · DOI
  23. Choong ML Yang HH McNiece I MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis Exp Hematol 2007 35 551 564 17379065 10.1016/j.exphem.2006.12.002 · DOI · Paper page
  24. Lujambio A Ropero S Ballestar E Fraga MF Cerrato C Setien F Casado S Suarez-Gauthier A Sanchez-Cespedes M Git A Spiteri I Das PP Caldas C Miska E Esteller M Genetic unmasking of an epigenetically silenced microRNA in human cancer cells Cancer Res 2007 67 1424 1429 17308079 10.1158/0008-5472.CAN-06-4218 · DOI
  25. Nelson PT Baldwin DA Kloosterman WP Kauppinen S Plasterk RH Mourelatos Z RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain RNA 2006 12 187 191 16373485 10.1261/rna.2258506 PMC1370897 · DOI · Paper page
  26. Grossel MJ Hinds PW From cell cycle to differentiation: an expanding role for cdk6 Cell Cycle 2006 5 266 270 16410727
  27. Takaki T Fukasawa K Suzuki-Takahashi I Semba K Kitagawa M Taya Y Hirai H Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro J Biochem 2005 137 381 386 15809340 10.1093/jb/mvi050 · DOI
  28. Corsten MF Miranda R Kasmieh R Krichevsky AM Weissleder R Shah K MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas Cancer Res 2007 67 8994 9000 17908999 10.1158/0008-5472.CAN-07-1045 · DOI · Paper page
  29. Gaur A Jewell DA Liang Y Ridzon D Moore JH Chen C Ambros VR Israel MA Characterization of microRNA expression levels and their biological correlates in human cancer cell lines Cancer Res 2007 67 2456 2468 17363563 10.1158/0008-5472.CAN-06-2698 · DOI · Paper page
  30. Gillies JK Lorimer IA Regulation of p27Kip1 by miRNA 221/222 in glioblastoma Cell Cycle 2007 6 2005 2009 17721077
  31. Weber F Teresi RE Broelsch CE Frilling A Eng C A limited set of human microRNA is deregulated in follicular thyroid carcinoma J Clin Endocrinol Metab 2006 91 3584 3591 16822819 10.1210/jc.2006-0693 · DOI
  32. Nicholas MK Lukas RV Jafri NF Faoro L Salgia R Epidermal growth factor receptor – mediated signal transduction in the development and therapy of gliomas Clin Cancer Res 2006 12 7261 7270 17189397 10.1158/1078-0432.CCR-06-0874 · DOI
  33. Fomchenko EI Holland EC Platelet-derived growth factor-mediated gliomagenesis and brain tumor recruitment Neurosurg Clin N Am 2007 18 39 58 viii 17244553 10.1016/j.nec.2006.10.006 · DOI
  34. Lee J Kotliarova S Kotliarov Y Li A Su Q Donin NM Pastorino S Purow BW Christopher N Zhang W Park JK Fine HA Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines Cancer Cell 2006 9 391 403 16697959 10.1016/j.ccr.2006.03.030 · DOI
  35. Saito Y Liang G Egger G Friedman JM Chuang JC Coetzee GA Jones PA Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells Cancer Cell 2006 9 435 443 16766263 10.1016/j.ccr.2006.04.020 · DOI
  36. Cao X Pfaff SL Gage FH A functional study of miR-124 in the developing neural tube Genes Dev 2007 21 531 536 17344415 10.1101/gad.1519207 PMC1820895 · DOI
  37. Visvanathan J Lee S Lee B Lee JW Lee SK The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development Genes Dev 2007 21 744 749 17403776 10.1101/gad.1519107 PMC1838526 · DOI · Paper page
  38. Mathupala SP Guthikonda M Sloan AE RNAi based approaches to the treatment of malignant glioma Technol Cancer Res Treat 2006 5 261 269 16700622
  39. Hashizume R Ozawa T Gryaznov SM Bollen AW Lamborn KR Frey WH Deen DF New therapeutic approach for brain tumor: intranasal delivery of telomerase inhibitor GRN163 Neuro Oncol 2008 112 120 18287341 10.1215/15228517-2007-052 PMC2613813 · DOI
  40. Hayes ME Drummond DC Hong K Zheng WW Khorosheva VA Cohen JA Noble CO IV Park JW Marks JD Benz CC Kirpotin DB Increased target specificity of anti-HER2 genospheres by modification of surface charge and degree of PEGylation Mol Pharm 2006 3 726 736 17140260 10.1021/mp060040v · DOI
  41. Hayes ME Drummond DC Kirpotin DB Zheng WW Noble CO Park JW Marks JD Benz CC Hong K Genospheres: self-assembling nucleic acid-lipid nanoparticles suitable for targeted gene delivery Gene Ther 2006 13 646 651 16341056 10.1038/sj.gt.3302699 · DOI
  42. Saito R Krauze MT Noble CO Drummond DC Kirpotin DB Berger MS Park JW Bankiewicz KS Convection-enhanced delivery of Ls-TPT enables an effective, continuous, low-dose chemotherapy against malignant glioma xenograft model Neuro Oncol 2006 8 205 214 16723630 10.1215/15228517-2006-001 PMC1871954 · DOI
  43. Yamashita Y Krauze MT Kawaguchi T Noble CO Drummond DC Park JW Bankiewicz KS Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts Neuro Oncol 2007 9 20 28 17018695 10.1215/15228517-2006-016 PMC1828110 · DOI
  44. Pandita A Aldape KD Zadeh G Guha A James CD Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR Genes Chromosomes Cancer 2004 39 29 36 14603439 10.1002/gcc.10300 · DOI
  45. Sarkaria JN Yang L Grogan PT Kitange GJ Carlson BL Schroeder MA Galanis E Giannini C Wu W Dinca EB James CD 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 1167 1174 17363510 10.1158/1535-7163.MCT-06-0691 · DOI

Cited by

Sorted by citations

Authors
Silber, J., Lim, D. A., Petritsch, C., Persson, A. I., Maunakea, A. K., Yu, M., Vandenberg, S. R., Ginzinger, D. G., James, C. D., Costello, J. F., Bergers, G., Weiss, W. A., Alvarez-Buylla, A., & Hodgson, J. G.
Venue
BMC Medicine
Publisher
Springer Science and Business Media LLC
Published
2008-06-24
Volume
6
Issue
1
ISSN
1741-7015
DOI
10.1186/1741-7015-6-14
PMC
PMC2443372
Cited by
765
References
5
Language
en
Licence
www.springer.com/tdm (unspecified)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review