Skip to main content
Top
Published in: Radiation Oncology 1/2011

Open Access 01-12-2011 | Research

MicroRNA expression profiles in human cancer cells after ionizing radiation

Authors: Olivier M Niemoeller, Maximilian Niyazi, Stefanie Corradini, Franz Zehentmayr, Minglun Li, Kirsten Lauber, Claus Belka

Published in: Radiation Oncology | Issue 1/2011

Login to get access

Abstract

Introduction

MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines.

Materials and methods

1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the "Geniom Biochip MPEA homo sapiens".

Results

Hierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered.

Conclusion

Ionizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5CrossRefPubMed Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5CrossRefPubMed
2.
go back to reference Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM: Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005, 433: 769-773. 10.1038/nature03315CrossRefPubMed Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM: Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005, 433: 769-773. 10.1038/nature03315CrossRefPubMed
3.
go back to reference He L, He XY, Lim LP, De Stanchina E, Xuan ZY, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, et al.: A microRNA component of the p53 tumour suppressor network. Nature 2007, 447: 1130-U1116. 10.1038/nature05939PubMedCentralCrossRefPubMed He L, He XY, Lim LP, De Stanchina E, Xuan ZY, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, et al.: A microRNA component of the p53 tumour suppressor network. Nature 2007, 447: 1130-U1116. 10.1038/nature05939PubMedCentralCrossRefPubMed
4.
go back to reference Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, et al.: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America 2005, 102: 13944-13949. 10.1073/pnas.0506654102PubMedCentralCrossRefPubMed Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, et al.: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America 2005, 102: 13944-13949. 10.1073/pnas.0506654102PubMedCentralCrossRefPubMed
5.
go back to reference Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al.: A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America 2006, 103: 2257-2261. 10.1073/pnas.0510565103PubMedCentralCrossRefPubMed Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al.: A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America 2006, 103: 2257-2261. 10.1073/pnas.0510565103PubMedCentralCrossRefPubMed
6.
go back to reference Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nature Reviews Cancer 2006, 6: 259-269. 10.1038/nrc1840CrossRefPubMed Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nature Reviews Cancer 2006, 6: 259-269. 10.1038/nrc1840CrossRefPubMed
7.
go back to reference Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, et al.: MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proceedings of the National Academy of Sciences of the United States of America 2004, 101: 11755-11760. 10.1073/pnas.0404432101PubMedCentralCrossRefPubMed Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, et al.: MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proceedings of the National Academy of Sciences of the United States of America 2004, 101: 11755-11760. 10.1073/pnas.0404432101PubMedCentralCrossRefPubMed
8.
go back to reference Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, et al.: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006, 9: 189-198. 10.1016/j.ccr.2006.01.025CrossRefPubMed Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, et al.: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006, 9: 189-198. 10.1016/j.ccr.2006.01.025CrossRefPubMed
9.
go back to reference Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, et al.: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Research 2004, 64: 3753-3756. 10.1158/0008-5472.CAN-04-0637CrossRefPubMed Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, et al.: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Research 2004, 64: 3753-3756. 10.1158/0008-5472.CAN-04-0637CrossRefPubMed
10.
go back to reference Weidhaas JB, Babar L, Nallur SM, Trang P, Roush S, Boehm N, Gillespie E, Slack FJ: MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Research 2007, 67: 11111-11116. 10.1158/0008-5472.CAN-07-2858CrossRefPubMed Weidhaas JB, Babar L, Nallur SM, Trang P, Roush S, Boehm N, Gillespie E, Slack FJ: MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Research 2007, 67: 11111-11116. 10.1158/0008-5472.CAN-07-2858CrossRefPubMed
11.
go back to reference Kato M, Paranjape T, Ullrich R, Nallur S, Gillespie E, Keane K, Esquela-Kerscher A, Weidhaas JB, Slack FJ: The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells. Oncogene 2009, 28: 2419-2424. 10.1038/onc.2009.106PubMedCentralCrossRefPubMed Kato M, Paranjape T, Ullrich R, Nallur S, Gillespie E, Keane K, Esquela-Kerscher A, Weidhaas JB, Slack FJ: The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells. Oncogene 2009, 28: 2419-2424. 10.1038/onc.2009.106PubMedCentralCrossRefPubMed
12.
go back to reference Maes OC, An J, Sarojini H, Wu HL, Wang E: Changes in MicroRNA Expression Patterns in Human Fibroblasts After Low-LET Radiation. Journal of Cellular Biochemistry 2008, 105: 824-834. 10.1002/jcb.21878CrossRefPubMed Maes OC, An J, Sarojini H, Wu HL, Wang E: Changes in MicroRNA Expression Patterns in Human Fibroblasts After Low-LET Radiation. Journal of Cellular Biochemistry 2008, 105: 824-834. 10.1002/jcb.21878CrossRefPubMed
13.
go back to reference Ilnytskyy Y, Koturbash I, Kovalchuk O: Radiation-Induced Bystander Effects In Vivo are Epigenetically Regulated in a Tissue-Specific Manner. Environmental and Molecular Mutagenesis 2009, 50: 105-113. 10.1002/em.20440CrossRefPubMed Ilnytskyy Y, Koturbash I, Kovalchuk O: Radiation-Induced Bystander Effects In Vivo are Epigenetically Regulated in a Tissue-Specific Manner. Environmental and Molecular Mutagenesis 2009, 50: 105-113. 10.1002/em.20440CrossRefPubMed
14.
go back to reference Tian S, Huang S, Wu S, Guo W, Li J, He X: MicroRNA-1285 inhibits the expression of p53 by directly targeting its 3' untranslated region. Biochem Biophys Res Commun 396: 435-439. 10.1016/j.bbrc.2010.04.112 Tian S, Huang S, Wu S, Guo W, Li J, He X: MicroRNA-1285 inhibits the expression of p53 by directly targeting its 3' untranslated region. Biochem Biophys Res Commun 396: 435-439. 10.1016/j.bbrc.2010.04.112
15.
go back to reference Ding J, Huang SL, Wu SQ, Zhao YJ, Liang LH, Yan MX, Ge C, Yao J, Chen TY, Wan DF, et al.: Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nature Cell Biology 2010, 12: 390-U208. 10.1038/ncb2039CrossRefPubMed Ding J, Huang SL, Wu SQ, Zhao YJ, Liang LH, Yan MX, Ge C, Yao J, Chen TY, Wan DF, et al.: Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nature Cell Biology 2010, 12: 390-U208. 10.1038/ncb2039CrossRefPubMed
16.
go back to reference Rogler CE, Levoci L, Ader T, Massimi A, Tchaikovskaya T, Norel R, Rogler LE: MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads. Hepatology 2009, 50: 575-584. 10.1002/hep.22982CrossRefPubMed Rogler CE, Levoci L, Ader T, Massimi A, Tchaikovskaya T, Norel R, Rogler LE: MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads. Hepatology 2009, 50: 575-584. 10.1002/hep.22982CrossRefPubMed
17.
go back to reference Blobe GC, Schiemann WP, Lodish HF: Mechanisms of disease: Role of transforming growth factor beta in human disease. New England Journal of Medicine 2000, 342: 1350-1358. 10.1056/NEJM200005043421807CrossRefPubMed Blobe GC, Schiemann WP, Lodish HF: Mechanisms of disease: Role of transforming growth factor beta in human disease. New England Journal of Medicine 2000, 342: 1350-1358. 10.1056/NEJM200005043421807CrossRefPubMed
18.
go back to reference Blower PE, Chung JH, Verducci JS, Lin SL, Park JK, Dai ZY, Liu CG, Schmittgen TD, Reinhold WC, Croce CM, et al.: MicroRNAs modulate the chemosensitivity of tumor cells. Molecular Cancer Therapeutics 2008, 7: 1-9. 10.1158/1535-7163.MCT-07-0573CrossRefPubMed Blower PE, Chung JH, Verducci JS, Lin SL, Park JK, Dai ZY, Liu CG, Schmittgen TD, Reinhold WC, Croce CM, et al.: MicroRNAs modulate the chemosensitivity of tumor cells. Molecular Cancer Therapeutics 2008, 7: 1-9. 10.1158/1535-7163.MCT-07-0573CrossRefPubMed
19.
go back to reference Schmidtullrich RK, Valerie KC, Chan W, McWilliams D: Altered Expression of Epidermal Growth-Factor Receptor and Estrogen-Receptor In Mcf-7 Cells After Single and Repeated Radiation Exposures. International Journal of Radiation Oncology Biology Physics 1994, 29: 813-819. 10.1016/0360-3016(94)90570-3CrossRef Schmidtullrich RK, Valerie KC, Chan W, McWilliams D: Altered Expression of Epidermal Growth-Factor Receptor and Estrogen-Receptor In Mcf-7 Cells After Single and Repeated Radiation Exposures. International Journal of Radiation Oncology Biology Physics 1994, 29: 813-819. 10.1016/0360-3016(94)90570-3CrossRef
20.
go back to reference Goetze K, Scholz M, Taucher-Scholz G, Mueller-Klieser W: The impact of conventional and heavy ion irradiation on tumor cell migration in vitro. International Journal of Radiation Biology 2007, 83: 889-896. 10.1080/09553000701753826CrossRefPubMed Goetze K, Scholz M, Taucher-Scholz G, Mueller-Klieser W: The impact of conventional and heavy ion irradiation on tumor cell migration in vitro. International Journal of Radiation Biology 2007, 83: 889-896. 10.1080/09553000701753826CrossRefPubMed
21.
go back to reference Wild-Bode C, Weller M, Rimner A, Dichgans J, Wick W: Sublethal irradiation promotes migration and invasiveness of glioma cells: Implications for radiotherapy of human glioblastoma. Cancer Research 2001, 61: 2744-2750.PubMed Wild-Bode C, Weller M, Rimner A, Dichgans J, Wick W: Sublethal irradiation promotes migration and invasiveness of glioma cells: Implications for radiotherapy of human glioblastoma. Cancer Research 2001, 61: 2744-2750.PubMed
22.
go back to reference 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. 10.1016/j.cell.2005.01.014CrossRefPubMed 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. 10.1016/j.cell.2005.01.014CrossRefPubMed
23.
go back to reference Oh JS, Kim JJ, Byun JY, Kim IA: Lin28-Let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras. International Journal of Radiation Oncology Biology Physics 2010, 76: 5-8. 10.1016/j.ijrobp.2009.08.028CrossRef Oh JS, Kim JJ, Byun JY, Kim IA: Lin28-Let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras. International Journal of Radiation Oncology Biology Physics 2010, 76: 5-8. 10.1016/j.ijrobp.2009.08.028CrossRef
Metadata
Title
MicroRNA expression profiles in human cancer cells after ionizing radiation
Authors
Olivier M Niemoeller
Maximilian Niyazi
Stefanie Corradini
Franz Zehentmayr
Minglun Li
Kirsten Lauber
Claus Belka
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2011
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-6-29

Other articles of this Issue 1/2011

Radiation Oncology 1/2011 Go to the issue