Skip to main content
Erschienen in: Tumor Biology 6/2015

01.06.2015 | Research Article

Differential expression of microRNAs in postoperative radiotherapy sensitive and resistant patients with glioblastoma multiforme

verfasst von: He-ming Wu, Han-dong Wang, Yong Tang, You-wu Fan, Yue-bing Hu, Mamatemin Tohti, Xiao-ke Hao, Wu-ting Wei, Yong Wu

Erschienen in: Tumor Biology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and more resistant to radiotherapy. However, hetero-radiosensitivity occurs in different patients. MicroRNAs (miRNAs) play important roles in the initiation and progression of a multitude of tumors. The study aims to examine the different microRNAs expression profiles of postoperative radiotherapy sensitive and resistant patients with GBM, to make an inquiry about their potential role and discover a certain set of radio-sensitivity markers. Three paired samples from six GBM patients who had only been treated with postoperative radiotherapy were selected, and then, they were divided into radiotherapy sensitive group and resistant group according to their overall survivals, local recurrence rates, and Karnofsky Performance Scale scores. Expression profiles of miRNAs in these two groups were determined by the method of microarray assay. Comparing with resistant patients, 13 miRNAs were significantly upregulated and 10 miRNAs were greatly downregulated in sensitive group. Among them, four miRNAs were validated by quantitative RT-PCR. The differentially expressed miRNAs and their putative target genes were revealed by bioformatic analysis to play a role in cell signaling, proliferation, aging, and death. High-enrichment pathway analysis identified that some classical pathways participated in numerous metabolic processes, especially in cell cycle regulation, such as mTOR, MAPK, TGF-beta, and PI3K-Akt signaling pathways. Our research will contribute to identifying clinical diagnostic markers and therapeutic targets in the treatment of GBM by postoperative radiotherapy.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Huang Z, Cheng L, Guryanova OA, Wu Q, Bao S. Cancer stem cells in glioblastoma–molecular signaling and therapeutic targeting. Protein & cell. 2010;1:638–55.CrossRef Huang Z, Cheng L, Guryanova OA, Wu Q, Bao S. Cancer stem cells in glioblastoma–molecular signaling and therapeutic targeting. Protein & cell. 2010;1:638–55.CrossRef
2.
Zurück zum Zitat Takebe N, Harris PJ, Warren RQ, Ivy SP. Targeting cancer stem cells by inhibiting wnt, notch, and hedgehog pathways. Nat Rev Clin Oncol. 2011;8:97–106.CrossRefPubMed Takebe N, Harris PJ, Warren RQ, Ivy SP. Targeting cancer stem cells by inhibiting wnt, notch, and hedgehog pathways. Nat Rev Clin Oncol. 2011;8:97–106.CrossRefPubMed
4.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.CrossRefPubMed
5.
Zurück zum Zitat Gonzalez-Gomez P, Sanchez P, Mira H. Micrornas as regulators of neural stem cell-related pathways in glioblastoma multiforme. Mol Neurobiol. 2011;44:235–49.CrossRefPubMed Gonzalez-Gomez P, Sanchez P, Mira H. Micrornas as regulators of neural stem cell-related pathways in glioblastoma multiforme. Mol Neurobiol. 2011;44:235–49.CrossRefPubMed
6.
Zurück zum Zitat Joki T, Carroll RS, Dunn IF, Zhang J, Abe T, Black PM. Assessment of alterations in gene expression in recurrent malignant glioma after radiotherapy using complementary deoxyribonucleic acid microarrays. Neurosurgery. 2001;48:195–201. discussion 201–192.PubMed Joki T, Carroll RS, Dunn IF, Zhang J, Abe T, Black PM. Assessment of alterations in gene expression in recurrent malignant glioma after radiotherapy using complementary deoxyribonucleic acid microarrays. Neurosurgery. 2001;48:195–201. discussion 201–192.PubMed
7.
Zurück zum Zitat Chaudhry MA, Sachdeva H, Omaruddin RA. Radiation-induced micro-RNA modulation in glioblastoma cells differing in DNA-repair pathways. DNA Cell Biol. 2010;29:553–61.CrossRefPubMed Chaudhry MA, Sachdeva H, Omaruddin RA. Radiation-induced micro-RNA modulation in glioblastoma cells differing in DNA-repair pathways. DNA Cell Biol. 2010;29:553–61.CrossRefPubMed
8.
Zurück zum Zitat Novakova J, Slaby O, Vyzula R, Michalek J. Microrna involvement in glioblastoma pathogenesis. Biochem Biophys Res Commun. 2009;386:1–5.CrossRefPubMed Novakova J, Slaby O, Vyzula R, Michalek J. Microrna involvement in glioblastoma pathogenesis. Biochem Biophys Res Commun. 2009;386:1–5.CrossRefPubMed
9.
Zurück zum Zitat Xiong J, Bing Z, Su Y, Deng D, Peng X. An integrated mrna and microrna expression signature for glioblastoma multiforme prognosis. PLoS One. 2014;9:e98419.CrossRefPubMedPubMedCentral Xiong J, Bing Z, Su Y, Deng D, Peng X. An integrated mrna and microrna expression signature for glioblastoma multiforme prognosis. PLoS One. 2014;9:e98419.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Zhang W, Zhang J, Yan W, You G, Bao Z, Li S, et al. Whole-genome microRNA expression profiling identifies a 5-microrna signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme. Cancer. 2013;119:814–24.CrossRefPubMed Zhang W, Zhang J, Yan W, You G, Bao Z, Li S, et al. Whole-genome microRNA expression profiling identifies a 5-microrna signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme. Cancer. 2013;119:814–24.CrossRefPubMed
11.
Zurück zum Zitat Cellini F, Morganti AG, Genovesi D, Silvestris N, Valentini V. Role of microRNA in response to ionizing radiations: Evidences and potential impact on clinical practice for radiotherapy. Molecules. 2014;19:5379–401.CrossRefPubMed Cellini F, Morganti AG, Genovesi D, Silvestris N, Valentini V. Role of microRNA in response to ionizing radiations: Evidences and potential impact on clinical practice for radiotherapy. Molecules. 2014;19:5379–401.CrossRefPubMed
12.
Zurück zum Zitat Wang XC, Du LQ, Tian LL, Wu HL, Jiang XY, Zhang H, et al. Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer. Lung Cancer. 2011;72:92–9.CrossRefPubMed Wang XC, Du LQ, Tian LL, Wu HL, Jiang XY, Zhang H, et al. Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer. Lung Cancer. 2011;72:92–9.CrossRefPubMed
13.
Zurück zum Zitat Teo MT, Landi D, Taylor CF, Elliott F, Vaslin L, Cox DG, et al. The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes. Carcinogenesis. 2012;33:581–6.CrossRefPubMed Teo MT, Landi D, Taylor CF, Elliott F, Vaslin L, Cox DG, et al. The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes. Carcinogenesis. 2012;33:581–6.CrossRefPubMed
14.
Zurück zum Zitat Liu S, Yin F, Zhang J, Wicha MS, Chang AE, Fan W, et al. Regulatory roles of miRNA in the human neural stem cell transformation to glioma stem cells. J Cell Biochem. 2014;115:1368–80.CrossRefPubMed Liu S, Yin F, Zhang J, Wicha MS, Chang AE, Fan W, et al. Regulatory roles of miRNA in the human neural stem cell transformation to glioma stem cells. J Cell Biochem. 2014;115:1368–80.CrossRefPubMed
15.
Zurück zum Zitat Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005;334:1351–8.CrossRefPubMed Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005;334:1351–8.CrossRefPubMed
16.
Zurück zum Zitat Niemoeller OM, Niyazi M, Corradini S, Zehentmayr F, Li M, Lauber K, et al. Microrna expression profiles in human cancer cells after ionizing radiation. Radiat Oncol. 2011;6:29.CrossRefPubMedPubMedCentral Niemoeller OM, Niyazi M, Corradini S, Zehentmayr F, Li M, Lauber K, et al. Microrna expression profiles in human cancer cells after ionizing radiation. Radiat Oncol. 2011;6:29.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Kozomara A, Griffiths-Jones S. Mirbase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42:D68–73.CrossRefPubMed Kozomara A, Griffiths-Jones S. Mirbase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42:D68–73.CrossRefPubMed
18.
Zurück zum Zitat 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;23:997–1003.PubMed 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;23:997–1003.PubMed
19.
Zurück zum Zitat Ruan WK, Shi Y, Wang J. Expression of miR-129-5p in glioma and its effect on glycometabolism and growth of human glioma cells. Jiangsu Med J. 2013;39:48–54. Ruan WK, Shi Y, Wang J. Expression of miR-129-5p in glioma and its effect on glycometabolism and growth of human glioma cells. Jiangsu Med J. 2013;39:48–54.
Metadaten
Titel
Differential expression of microRNAs in postoperative radiotherapy sensitive and resistant patients with glioblastoma multiforme
verfasst von
He-ming Wu
Han-dong Wang
Yong Tang
You-wu Fan
Yue-bing Hu
Mamatemin Tohti
Xiao-ke Hao
Wu-ting Wei
Yong Wu
Publikationsdatum
01.06.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3121-z

Weitere Artikel der Ausgabe 6/2015

Tumor Biology 6/2015 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.