Advertisement

Tumor Biology

, Volume 34, Issue 4, pp 1969–1978 | Cite as

MicroRNAs involved in chemo- and radioresistance of high-grade gliomas

  • Andrej Besse
  • Jiri Sana
  • Pavel Fadrus
  • Ondrej Slaby
Review

Abstract

High-grade gliomas (HGGs) are malignant primary brain tumors of glial cell origin. Despite optimal course of treatment, including maximal surgical resection followed by adjuvant chemo- and/or radiotherapy, the prognosis still remains poor. The main reason is the commonly occurring chemo- and radioresistance of these tumors. In recent years, several signaling pathways, especially PI3K/AKT and ATM/CHK2/p53, have been linked to the resistance of gliomas. Moreover, additional studies have shown that these pathways are significantly regulated by microRNAs (miRNAs), short endogenous RNA molecules that modulate gene expression and control many biological processes including apoptosis, proliferation, cell cycle, invasivity, and angiogenesis. MiRNAs are not only highly deregulated in gliomas, their expression signatures have also been shown to predict prognosis and therapy response. Therefore, they present promising biomarkers and therapeutic targets that might overcome the resistance to treatment and improve prognosis of glioma patients. In this review, we summarize the current knowledge of the functional role of miRNAs in gliomas resistance to chemo- and radiotherapy.

Keywords

microRNA Glioma Chemoresistance Radioresistance 

Notes

Acknowledgment

This work was supported by grants of Internal Grant Agency of the Czech Ministry of Health no. NT13514-4/2012 and NT11214-4/2010; project “CEITEC—Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068); and by the Institutional Resources for Supporting the Research Organization provided by the Czech Ministry of Health in 2012. The authors would like to thank Martin Kolnik for proofreading the article.

Conflicts of interest

None.

References

  1. 1.
    Srinivasan S, Patric IR, Somasundaram K. A ten-microRNA expression signature predicts survival in glioblastoma. PLoS One. 2011;6(3):e17438. doi: 10.1371/journal.pone.0017438.PubMedCrossRefGoogle Scholar
  2. 2.
    Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, Wang SS, et al. Genome-wide association study of glioma and meta-analysis. Hum Genet. 2012. doi: 10.1007/s00439-012-1212-0.
  3. 3.
    van den Bent MJ. Anaplastic oligodendroglioma and oligoastrocytoma. Neurol Clin. 2007;25(4):1089–109. doi: 10.1016/j.ncl.2007.07.013. ix–x.PubMedCrossRefGoogle Scholar
  4. 4.
    Butowski NA, Sneed PK, Chang SM. Diagnosis and treatment of recurrent high-grade astrocytoma. J Clin Oncol. 2006;24(8):1273–80. doi: 10.1200/jco.2005.04.7522.PubMedCrossRefGoogle Scholar
  5. 5.
    Chen L, Han L, Shi Z, Zhang K, Liu Y, Zheng Y, et al. LY294002 enhances cytotoxicity of temozolomide in glioma by down-regulation of the PI3K/Akt pathway. Mol Med Rep. 2012;5(2):575–9. doi: 10.3892/mmr.2011.674.PubMedGoogle Scholar
  6. 6.
    Gwak HS, Kim TH, Jo GH, Kim YJ, Kwak HJ, Kim JH, et al. Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PLoS One. 2012;7(10):e47449. doi: 10.1371/journal.pone.0047449.PubMedCrossRefGoogle Scholar
  7. 7.
    Squatrito M, Brennan CW, Helmy K, Huse JT, Petrini JH, Holland EC. Loss of ATM/Chk2/p53 pathway components accelerates tumor development and contributes to radiation resistance in gliomas. Cancer Cell. 2010;18(6):619–29. doi: 10.1016/j.ccr.2010.10.034.PubMedCrossRefGoogle Scholar
  8. 8.
    Wang J, Wakeman TP, Lathia JD, Hjelmeland AB, Wang X-F, White RR, et al. Notch promotes radioresistance of glioma stem cells. Stem Cells. 2010;28(1):17–28. doi: 10.1002/stem.261.PubMedGoogle Scholar
  9. 9.
    Yamada R, Nakano I. Glioma stem cells: their role in chemoresistance. World Neurosurg. 2012;77(2):237–40. doi: 10.1016/j.wneu.2012.01.004.PubMedCrossRefGoogle Scholar
  10. 10.
    Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001;107(7):823–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Auffinger B, Thaci B, Ahmed A, Ulasov I, Lesniak MS. (2012) MicroRNA targeting as a therapeutic strategy against glioma. Curr Mol Med. Epub ahead of printGoogle Scholar
  12. 12.
    Yu KN, Han W. Ionizing radiation, DNA double strand break, and mutation. In: Urbano KV, editor. Advances in Genetics Research, 4. New York: Nova Science Publishers, Inc; 2010. ISBN 978-1-61728-764-0.Google Scholar
  13. 13.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi: 10.1056/NEJMoa043330.PubMedCrossRefGoogle Scholar
  14. 14.
    Lee KM, Choi EJ, Kim IA. microRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling. Radiother Oncol. 2011;101(1):171–6. doi: 10.1016/j.radonc.2011.05.050.PubMedCrossRefGoogle Scholar
  15. 15.
    Narayan RS, Fedrigo CA, Stalpers LJ, Baumert BG, Sminia P. Targeting the Akt-pathway to improve radiosensitivity in glioblastoma. Curr Pharm Des. 2013;19(5):951–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Kwiatkowska A, Symons M. Signaling determinants of glioma cell invasion. Adv Exp Med Biol. 2013;986:121–41. doi: 10.1007/978-94-007-4719-7_7.PubMedCrossRefGoogle Scholar
  17. 17.
    Guillamo J-S, de Boüard S, Valable S, Marteau L, Leuraud P, Marie Y, et al. Molecular mechanisms underlying effects of epidermal growth factor receptor inhibition on invasion, proliferation, and angiogenesis in experimental glioma. Clin Cancer Res. 2009;15(11):3697–704. doi: 10.1158/1078-0432.ccr-08-2042.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen G, Zhu W, Shi D, Lv L, Zhang C, Liu P, et al. MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2. Oncol Rep. 2010;23(4):997–1003.PubMedGoogle Scholar
  19. 19.
    Hara T, Omura-Minamisawa M, Kang Y, Cheng C, Inoue T. Flavopiridol potentiates the cytotoxic effects of radiation in radioresistant tumor cells in which p53 is mutated or Bcl-2 is overexpressed. Int J Radiat Oncol Biol Phys. 2008;71(5):1485–95. doi: 10.1016/j.ijrobp.2008.03.039.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhou X, Ren Y, Moore L, Mei M, You Y, Xu P, et al. Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Invest. 2010;90(2):144–55. doi: 10.1038/labinvest.2009.126.PubMedCrossRefGoogle Scholar
  21. 21.
    Huse JT, Brennan C, Hambardzumyan D, Wee B, Pena J, Rouhanifard SH, et al. The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev. 2009;23(11):1327–37. doi: 10.1101/gad.1777409.PubMedCrossRefGoogle Scholar
  22. 22.
    Kim H, Huang W, Jiang X, Pennicooke B, Park PJ, Johnson MD. Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. Proc Natl Acad Sci USA. 2010;107(5):2183–8. doi: 10.1073/pnas.0909896107.PubMedCrossRefGoogle Scholar
  23. 23.
    Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M, et al. microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res. 2008;68(10):3566–72. doi: 10.1158/0008-5472.can-07-6639.PubMedCrossRefGoogle Scholar
  24. 24.
    Nan Y, Han L, Zhang A, Wang G, Jia Z, Yang Y, et al. MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res. 2010;1359:14–21. doi: 10.1016/j.brainres.2010.08.074.PubMedCrossRefGoogle Scholar
  25. 25.
    Fell VL, Schild-Poulter C. Ku regulates signaling to DNA damage response pathways through the Ku70 von Willebrand A domain. Mol Cell Biol. 2012;32(1):76–87. doi: 10.1128/mcb.05661-11.PubMedCrossRefGoogle Scholar
  26. 26.
    Westhoff MA, Kandenwein JA, Karl S, Vellanki SHK, Braun V, Eramo A, et al. The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair. Oncogene. 2009;28(40):3586–96. doi: 10.1038/onc.2009.215.PubMedCrossRefGoogle Scholar
  27. 27.
    Ng WL, Yan D, Zhang X, Mo Y-Y, Wang Y. Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J. DNA Repair. 2010;9(11):1170–5. doi: 10.1016/j.dnarep.2010.08.007.PubMedCrossRefGoogle Scholar
  28. 28.
    Chaudhry MA, Sachdeva H, Omaruddin RA. Radiation-induced micro-RNA modulation in glioblastoma cells differing in DNA-repair pathways. DNA Cell Biol. 2010;29(9):553–61. doi: 10.1089/dna.2009.0978.PubMedCrossRefGoogle Scholar
  29. 29.
    Chaudhry MA, Kreger B, Omaruddin RA. Transcriptional modulation of micro-RNA in human cells differing in radiation sensitivity. Int J Radiat Biol. 2010;86(7):569–83. doi: 10.3109/09553001003734568.PubMedCrossRefGoogle Scholar
  30. 30.
    Lin Y-X, Yu F, Gao N, Sheng J-P, Qiu J-Z, Hu B-C. microRNA-143 protects cells from DNA damage-induced killing by downregulating FHIT expression. Cancer Biother Radiopharm. 2011;26(3):365–72. doi: 10.1089/cbr.2010.0914.PubMedCrossRefGoogle Scholar
  31. 31.
    Babar IA, Czochor J, Steinmetz A, Weidhaas JB, Glazer PM, Slack FJ. Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells. Cancer Biol Ther. 2011;12(10):908–14. doi: 10.4161/cbt.12.10.17681.PubMedCrossRefGoogle Scholar
  32. 32.
    Yan D, Ng WL, Zhang X, Wang P, Zhang Z, Mo Y-Y, et al. Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. PLoS ONE. 2010;5(7):e11397. doi: 10.1371/journal.pone.0011397.PubMedCrossRefGoogle Scholar
  33. 33.
    Chen S, Wang H, Ng WL, Curran WJ, Wang Y. Radiosensitizing effects of ectopic miR-101 on non-small-cell lung cancer cells depend on the endogenous miR-101 level. Int J Radiat Oncol Biol Phys. 2011;81(5):1524–9. doi: 10.1016/j.ijrobp.2011.05.031.PubMedCrossRefGoogle Scholar
  34. 34.
    Nakano I, Kornblum HI. Brain tumor stem cells. Pediatr Res. 2006;59(4 Pt 2):54R–8R. doi: 10.1203/01.pdr.0000203568.63482.f9.PubMedCrossRefGoogle Scholar
  35. 35.
    Mueller AC, Sun D, Dutta A. The miR-99 family regulates the DNA damage response through its target SNF2H. Oncogene. 2012. doi: 10.1038/onc.2012.131.Google Scholar
  36. 36.
    Mirzayans R, Andrais B, Scott A, Murray D. New insights into p53 signaling and cancer cell response to DNA damage: implications for cancer therapy. J Biomed Biotechnol. 2012. doi: 10.1155/2012/170325.PubMedGoogle Scholar
  37. 37.
    Le MTN, Teh C, Shyh-Chang N, Xie H, Zhou B, Korzh V, et al. MicroRNA-125b is a novel negative regulator of p53. Genes Dev. 2009;23(7):862–76. doi: 10.1101/gad.1767609.PubMedCrossRefGoogle Scholar
  38. 38.
    Luan S, Sun L, Huang F. MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251. Arch Med Res. 2010;41(2):67–74. doi: 10.1016/j.arcmed.2010.02.007.PubMedCrossRefGoogle Scholar
  39. 39.
    Sasaki A, Udaka Y, Tsunoda Y, Yamamoto G, Tsuji M, Oyamada H, et al. Analysis of p53 and miRNA expression after irradiation of glioblastoma cell lines. Anticancer Res. 2012;32(11):4709–13.PubMedGoogle Scholar
  40. 40.
    Carmo A, Carvalheiro H, Crespo I, Nunes I, Lopes MC. Effect of temozolomide on the U-118 glioma cell line. Oncol Lett. 2011;2(6):1165–70. doi: 10.3892/ol.2011.406.PubMedGoogle Scholar
  41. 41.
    Darkes MJM, Plosker GL, Jarvis B. Temozolomide: a review of its use in the treatment of malignant gliomas, malignant melanoma and other advanced cancers. Am J Cancer. 2002;1(1):55–80.CrossRefGoogle Scholar
  42. 42.
    Sharma S, Salehi F, Scheithauer BW, Rotondo F, Syro LV, Kovacs K. Role of MGMT in tumor development, progression, diagnosis, treatment, and prognosis. Anticancer Res. 2009;29(10):3759–68.PubMedGoogle Scholar
  43. 43.
    Slaby O, Lakomy R, Fadrus P, Hrstka R, Kren L, Lzicarova E, et al. MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients. Neoplasma. 2010;57(3):264–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Zhang W, Zhang J, Hoadley K, Kushwaha D, Ramakrishnan V, Li S, et al. miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression. Neuro Oncol. 2012;14(6):712–9. doi: 10.1093/neuonc/nos089.PubMedCrossRefGoogle Scholar
  45. 45.
    Zhang S, Wan Y, Pan T, Gu X, Qian C, Sun G, et al. MicroRNA-21 inhibitor sensitizes human glioblastoma U251 stem cells to chemotherapeutic drug temozolomide. J Mol Neurosci. 2012;47(2):346–56. doi: 10.1007/s12031-012-9759-8.PubMedCrossRefGoogle Scholar
  46. 46.
    Ren Y, Kang C-S, Yuan X-B, Zhou X, Xu P, Han L, et al. Co-delivery of as-miR-21 and 5-FU by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro. J Biomater Sci Polym Ed. 2010;21(3):303–14. doi: 10.1163/156856209x415828.PubMedCrossRefGoogle Scholar
  47. 47.
    Shi L, Chen J, Yang J, Pan T, Zhang S, Wang Z. MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res. 2010;1352:255–64. doi: 10.1016/j.brainres.2010.07.009.PubMedCrossRefGoogle Scholar
  48. 48.
    Zhou X, Zhang J, Jia Q, Ren Y, Wang Y, Shi L, et al. Reduction of miR-21 induces glioma cell apoptosis via activating caspase 9 and 3. Oncol Rep. 2010;24(1):195–201.PubMedGoogle Scholar
  49. 49.
    Wong STS, Zhang X-Q, Zhuang JT-F, Chan H-L, Li C-H, Leung GKK. MicroRNA-21 inhibition enhances in vitro chemosensitivity of temozolomide-resistant glioblastoma cells. Anticancer Res. 2012;32(7):2835–41.PubMedGoogle Scholar
  50. 50.
    Li Y, Li W, Yang Y, Lu Y, He C, Hu G, et al. MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme. Brain Res. 2009;1286:13–28. doi: 10.1016/j.brainres.2009.06.053.PubMedCrossRefGoogle Scholar
  51. 51.
    Chen L, Zhang J, Han L, Zhang A, Zhang C, Zheng Y, et al. Downregulation of miR-221/222 sensitizes glioma cells to temozolomide by regulating apoptosis independently of p53 status. Oncol Rep. 2012;27(3):854–60. doi: 10.3892/or.2011.1535.PubMedGoogle Scholar
  52. 52.
    Ujifuku K, Mitsutake N, Takakura S, Matsuse M, Saenko V, Suzuki K, et al. miR-195, miR-455-3p and miR-10a(*) are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. Cancer Lett. 2010;296(2):241–8. doi: 10.1016/j.canlet.2010.04.013.PubMedCrossRefGoogle Scholar
  53. 53.
    Zhang Q-Q, Xu H, Huang M-B, Ma L-M, Huang Q-J, Yao Q, et al. MicroRNA-195 plays a tumor-suppressor role in human glioblastoma cells by targeting signaling pathways involved in cellular proliferation and invasion. Neuro Oncol. 2012;14(3):278–87. doi: 10.1093/neuonc/nor216.PubMedCrossRefGoogle Scholar
  54. 54.
    Li W-Q, Li Y-M, Tao B-B, Lu Y-C, Hu G-H, Liu H-M, et al. Downregulation of ABCG2 expression in glioblastoma cancer stem cells with miRNA-328 may decrease their chemoresistance. Med Sci Monit. 2010;16(10):HY27–30.PubMedGoogle Scholar
  55. 55.
    Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G, et al. Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008;68(22):9125–30. doi: 10.1158/0008-5472.can-08-2629.PubMedCrossRefGoogle Scholar
  56. 56.
    Chen R, Nishimura MC, Bumbaca SM, Kharbanda S, Forrest WF, Kasman IM, et al. A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell. 2010;17(4):362–75. doi: 10.1016/j.ccr.2009.12.049.PubMedCrossRefGoogle Scholar
  57. 57.
    Ulasov IV, Nandi S, Dey M, Sonabend AM, Lesniak MS. Inhibition of Sonic hedgehog and Notch pathways enhances sensitivity of CD133(+) glioma stem cells to temozolomide therapy. Mol Med. 2011;17(1–2):103–12. doi: 10.2119/molmed.2010.00062.PubMedGoogle Scholar
  58. 58.
    Jeon H-M, Sohn Y-W, Oh S-Y, Oh S-Y, Kim S-H, Beck S, et al. ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer Res. 2011;71(9):3410–21. doi: 10.1158/0008-5472.can-10-3340.PubMedCrossRefGoogle Scholar
  59. 59.
    Yang Y-P, Chien Y, Chiou G-Y, Cherng J-Y, Wang M-L, Lo W-L, et al. Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials. 2012;33(5):1462–76. doi: 10.1016/j.biomaterials.2011.10.071.PubMedCrossRefGoogle Scholar
  60. 60.
    Yu X, Zhang W, Ning Q, Luo X. MicroRNA-34a inhibits human brain glioma cell growth by down-regulation of Notch1. J Huazhong Univ Sci Technol Med Sci. 2012;32(3):370–4. doi: 10.1007/s11596-012-0064-0.PubMedCrossRefGoogle Scholar
  61. 61.
    Li W-B, Ma M-W, Dong L-J, Wang F, Chen L-X, Li X-R. MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma multiforme. Cancer Biol Ther. 2011;12(6):477–83. doi: 10.4161/cbt.12.6.16300.PubMedCrossRefGoogle Scholar
  62. 62.
    Guessous F, Zhang Y, Kofman A, Catania A, Li Y, Schiff D, et al. microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle. 2010;9(6):1031–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, et al. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 2009;69(19):7569–76. doi: 10.1158/0008-5472.can-09-0529.PubMedCrossRefGoogle Scholar
  64. 64.
    Kefas B, Comeau L, Floyd DH, Seleverstov O, Godlewski J, Schmittgen T, et al. The neuronal microRNA miR-326 acts in a feedback loop with notch and has therapeutic potential against brain tumors. J Neurosci. 2009;29(48):15161–8. doi: 10.1523/jneurosci.4966-09.2009.PubMedCrossRefGoogle Scholar
  65. 65.
    Mei J, Bachoo R, Zhang C-L. MicroRNA-146a inhibits glioma development by targeting Notch1. Mol Cell Biol. 2011;31(17):3584–92. doi: 10.1128/mcb.05821-11.PubMedCrossRefGoogle Scholar
  66. 66.
    Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, et al. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 2008;6(14).Google Scholar
  67. 67.
    Shi L, Zhang J, Pan T, Zhou J, Gong W, Liu N, et al. MiR-125b is critical for the suppression of human U251 glioma stem cell proliferation. Brain Res. 2010;1312:120–6. doi: 10.1016/j.brainres.2009.11.056.PubMedCrossRefGoogle Scholar
  68. 68.
    Srinivasan S, Patric IRP, Somasundaram K. A ten-microRNA expression signature predicts survival in glioblastoma. PLoS ONE. 2011;6(3).Google Scholar
  69. 69.
    Lakomy R, Sana J, Hankeova S, Fadrus P, Kren L, Lzicarova E, et al. MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients. Cancer Sci. 2011;102(12):2186–90. doi: 10.1111/j.1349-7006.2011.02092.x.PubMedCrossRefGoogle Scholar
  70. 70.
    Poltronieri P, D’Urso PI, Mezzolla V, D’Urso OF. Potential of anti-cancer therapy based on anti-miR-155 oligonucleotides in glioma and brain tumours. Chem Biol Drug Des. 2013;81(1):79–84. doi: 10.1111/cbdd.12002.PubMedCrossRefGoogle Scholar
  71. 71.
    Shan SW, Fang L, Shatseva T, Rutnam ZJ, Yang X, Lu WY, et al. Mature MiR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7, and vimentin in different signal pathways. J Cell Sci. 2013. doi: 10.1242/jcs.122895.Google Scholar
  72. 72.
    Gu Y, Sun J, Groome LJ, Wang Y. Differential miRNA expression profiles between the first and third trimester human placentas. Am J Physiol Endocrinol Metab. 2013. doi: 10.1152/ajpendo.00660.2012.
  73. 73.
    Xu XM, Wang XB, Chen MM, Liu T, Li YX, Jia WH, et al. MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5. Cancer Lett. 2012;322(2):148–58. doi: 10.1016/j.canlet.2012.02.038.PubMedCrossRefGoogle Scholar
  74. 74.
    Liu M, Wang Z, Yang S, Zhang W, He S, Hu C, et al. TNF-alpha is a novel target of miR-19a. Int J Oncol. 2011;38(4):1013–22. doi: 10.3892/ijo.2011.924.PubMedGoogle Scholar
  75. 75.
    Liang Z, Li Y, Huang K, Wagar N, Shim H. Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN. Pharm Res. 2011;28(12):3091–100. doi: 10.1007/s11095-011-0570-y.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Andrej Besse
    • 1
    • 2
  • Jiri Sana
    • 1
    • 2
  • Pavel Fadrus
    • 3
  • Ondrej Slaby
    • 1
    • 2
  1. 1.Department of Comprehensive Cancer CareMasaryk Memorial Cancer InstituteBrnoCzech Republic
  2. 2.Central European Institute of Technology (CEITEC)Masaryk UniversityBrnoCzech Republic
  3. 3.Department of NeurosurgeryUniversity Hospital Brno, Faculty of Medicine, Masaryk UniversityBrnoCzech Republic

Personalised recommendations