Gene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation
Xiaoqing Li,
Jun Liu,
Rui Zhou,
Shi Huang,
Shiang Huang,
Xian-Ming Chen,
Xiaoqing Li
Institute of Hematology, Union Hospital, Wuhan, China
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Equal contribution to this study.
Search for more papers by this authorJun Liu
Institute of Hematology, Union Hospital, Wuhan, China
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Equal contribution to this study.
Search for more papers by this authorRui Zhou
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Search for more papers by this authorShi Huang
Burnham Institute for Medical Research, La Jolla, CA, USA
Search for more papers by this authorShiang Huang
Institute of Hematology, Union Hospital, Wuhan, China
Search for more papers by this authorXian-Ming Chen
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Search for more papers by this authorXiaoqing Li,
Jun Liu,
Rui Zhou,
Shi Huang,
Shiang Huang,
Xian-Ming Chen,
Xiaoqing Li
Institute of Hematology, Union Hospital, Wuhan, China
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Equal contribution to this study.
Search for more papers by this authorJun Liu
Institute of Hematology, Union Hospital, Wuhan, China
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Equal contribution to this study.
Search for more papers by this authorRui Zhou
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Search for more papers by this authorShi Huang
Burnham Institute for Medical Research, La Jolla, CA, USA
Search for more papers by this authorShiang Huang
Institute of Hematology, Union Hospital, Wuhan, China
Search for more papers by this authorXian-Ming Chen
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE
Search for more papers by this authorShiang Huang, Institute of Hematology, Union Hospital, Wuhan, China. E-mail: [email protected];Xian-Ming Chen, Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE 68178, USA. E-mail: [email protected]
Summary
Aberrant epigenetic regulation has recently been implicated in the downregulation of tumour suppressor microRNAs (miRNAs). Histone modification and DNA methylation can have different roles in gene silencing in cancer. To investigate whether histone modifications would contribute to the dysregulation of miRNAs in acute lymphoblastic leukaemia (ALL), the effect of a histone deacetylase inhibitor, trichostatin A (TSA), on miRNA expression profile was analysed by microarray assay in a precursor B-cell ALL cell line NALM-6. A total of 10 miRNAs were downregulated and 31 were upregulated significantly following TSA treatment. Among TSA-upregulated miRNAs, MIR22 is an extronic miRNA and resides in the second exon of the non-coding transcript MGC14376. Upregulation of MIR22 transcription was found in both NALM-6 cells and primary human ALL malignant cells treated with TSA. Whereas a CpG island was identified within the promoter element of MIR22, no promoter DNA methylation was detected in these cells. In contrast, accumulation of the repressive histone marker H3K27 trimethylation (H3K27triM) was indentified around the transcriptional start point of the gene, which was reduced by TSA treatment. Thus, accumulation of H3K27triM independent of promoter DNA methylation may be a novel epigenetic mechanism for MIR22 silencing in ALL.
Supporting Information
Table SI. Primer sequences.
Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.
| Filename | Description |
|---|---|
| BJH_7920_sm_Table S1.ppt247 KB | Supporting info item |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Bartel, D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.
- Baskerville, S. & Bartel, D.P. (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 11, 241–247.
- Baylin, S.B., Esteller, M., Rountree, M.R., Bachman, K.E., Schuebel, K. & Herman, J.G. (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Human Molecular Genetics, 10, 687–692.
- Brazma, A., Hingamp, P., Quackenbush, J., Sherlock, G., Spellman, P., Stoeckert, C., Aach, J., Ansorge, W., Ball, C.A., Causton, H.C., Gaasterland, T., Glenisson, P., Holstege, F.C., Kim, I.F., Markowitz, V., Matese, J.C., Parkinson, H., Robinson, A., Sarkans, U., Schulze-Kremer, S., Stewart, J., Taylor, R., Vilo, J. & Vingron, M. (2001) Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nature Genetics, 29, 365–371.
- Calin, G.A. & Croce, C.M. (2006) MicroRNA signatures in human cancers. Nature Reviews. Cancer, 6, 857–866.
- Calin, G.A., Dumitru, C.D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., Rassenti, L., Kipps, T., Negrini, M., Bullrich, F. & Croce, C.M. (2002) Frequent deletions and down-regulation of micro-RNA genes miR-15 and miR-16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 99, 15524–15529.
- Calin, G.A., Cimmino, A., Fabbri, M., Ferracin, M., Wojcik, S.E., Shimizu, M., Taccioli, C., Zanesi, N., Garzon, R., Aqeilan, R.I., Alder, H., Volinia, S., Rassenti, L., Liu, X., Liu, C.G., Kipps, T.J., Negrini, M. & Croce, C.M. (2008) miR-15a and miR-16-1 cluster functions in human leukemia. Proceedings of the National Academy of Sciences of the United States of America, 105, 5166–5171.
- Cameron, E.E., Bachman, K.E., Myohanen, S., Herman, J.G. & Baylin, S.B. (1999) Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nature Genetics, 21, 103–107.
- Cedar, H. & Bergman, Y. (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nature Reviews Genetics, 10, 295–304.
- Chang, T.C., Yu, D., Lee, Y.S., Wentzel, E.A., Arking, D.E., West, K.M., Dang, C.V., Thomas-Tikhonenko, A. & Mendell, J.T. (2008) Widespread microRNA repression by Myc contributes to tumorigenesis. Nature Genetics, 40, 43–50.
- Chen, C., Ridzon, D.A., Broomer, A.J., Zhou, Z., Lee, D.H., Nguyen, J.T., Barbisin, M., Xu, N.L., Mahuvakar, V.R., Andersen, M.R., Lao, K.Q., Livak, K.J. & Guegler, K.J. (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Research, 33, e179.
- Cimmino, A., Calin, G.A., Fabbri, M., Iorio, M.V., Ferracin, M., Shimizu, M., Wojcik, S.E., Aqeilan, R.I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C.G., Kipps, T.J., Negrini, M. & Croce, C.M. (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America, 102, 13944–13949.
- Esquela-Kerscher, A. & Slack, F.J. (2006) Oncomirs-microRNAs with a role in cancer. Nature Reviews. Cancer, 6, 259–269.
- Fahrner, J.A., Eguchi, S., Herman, J.G. & Baylin, S.B. (2002) Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Research, 62, 7213–7218.
- Fiskus, W., Pranpat, M., Balasis, M., Herger, B., Rao, R., Chinnaiyan, A., Atadja, P. & Bhalla, K. (2006) Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells. Molecular Cancer Therapeutics, 5, 3096–3104.
- Gong, A.Y., Zhou, R., Hu, G., Li, X., Splinter, P.L., O’Hara, S.P., LaRusso, N.F., Soukup, G.A., Dong, H. & Chen, X.M. (2009) MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. Journal of Immunology, 182, 1325–1333.
- Hayashita, Y., Osada, H., Tatematsu, Y., Yamada, H., Yanagisawa, K., Tomida, S., Yatabe, Y., Kawahara, K., Sekido, Y. & Takahashi, T. (2005) A polycistronic microRNA cluster, miR- 17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Research, 65, 9628–9632.
- He, L. & Hannon, G.J. (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nature Reviews Genetics, 5, 522–531.
- He, L., Thomson, J.M., Hemann, M.T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S.W., Hannon, G.J. & Hammond, S.M. (2005) A microRNA polycistron as a potential human oncogene. Nature, 435, 828–833.
- He, L., He, X., Lowe, S.W. & Hannon, G.J. (2007) microRNAs join the p53 network – another piece in the tumour-suppression puzzle. Nature Reviews. Cancer, 11, 819–822.
- Heintzman, N.D., Stuart, R.K., Hon, G., Fu, Y., Ching, C.W., Hawkins, R.D., Barrera, L.O., Van Calcar, S., Qu, C., Ching, K.A., Wang, W., Weng, Z., Green, R.D., Crawford, G.E. & Ren, B. (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nature Genetics, 39, 311–318.
- Iorio, M.V., Ferracin, M., Liu, C.G., Veronese, A., Spizzo, R., Sabbioni, S., Magri, E., Pedriali, M., Fabbri, M., Campiglio, M., Ménard, S., Palazzo, J.P., Rosenberg, A., Musiani, P., Volinia, S., Nenci, I., Calin, G.A., Querzoli, P., Negrini, M. & Croce, C.M. (2005) MicroRNA gene expression dysregulation in human breast cancer. Cancer Research, 65, 7065–7070.
- Jenuwein, T. & Allis, C.D. (2001) Translating the histone code. Science, 293, 1074–1080.
- Johnson, S.M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K.L., Brown, D. & Slack, F.J. (2005) RAS is regulated by the let-7 microRNA family. Cell, 120, 635–647.
- Kondo, Y., Shen, L., Cheng, A.S., Ahmed, S., Boumber, Y., Charo, C., Yamochi, T., Urano, T., Furukawa, K., Kwabi-Addo, B., Gold, D.L., Sekido, Y., Huang, T.H. & Issa, J.P. (2008) Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nature Genetics, 40, 741–750.
- Kozaki, K., Imoto, I., Mogi, S., Omura, K. & Inazawa, J. (2008) Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Research, 68, 2094–2105.
- Laird, P.W., Zijderveld, A., Linders, K., Rudnicki, M.A., Jaenisch, R. & Berns, A. (1991) Simplified mammalian DNA isolation procedure. Nucleic Acids Research, 19, 4293.
- Lehmann, U., Hasemeier, B., Christgen, M., Müller, M., Römermann, D., Länger, F. & Kreipe, H. (2008) Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. The Journal of Pathology, 214, 17–24.
- Lujambio, A., Ropero, S., Ballestar, E., Fraga, M.F., Cerrato, C., Setién, F., Casado, S., Suarez-Gauthier, A., Sanchez-Cespedes, M., Git, A., Spiteri, I., Das, P.P., Caldas, C., Miska, E. & Esteller, M. (2007) Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Research, 67, 1424–1429.
- Mi, S., Lu, J., Sun, M., Li, Z., Zhang, H., Neilly, M.B., Wang, Y., Qian, Z., Jin, J., Zhang, Y., Bohlander, S.K., Le Beau, M.M., Larson, R.A., Golub, T.R., Rowley, J.D. & Chen, J. (2007) MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proceedings of the National Academy of Sciences of the United States of America, 104, 19971–19976.
- Miska, E.A. (2005) How microRNAs control cell division, differentiation and death. Current Opinion in Genetics & Development, 15, 563–568.
- Ohm, J.E., McGarvey, K.M., Yu, X., Cheng, L., Schuebel, K.E., Cope, L., Mohammad, H.P., Chen, W., Daniel, V.C., Yu, W., Berman, D.M., Jenuwein, T., Pruitt, K., Sharkis, S.J., Watkins, D.N., Herman, J.G. & Baylin, S.B. (2007) A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nature Genetics, 39, 237–242.
- Pekarsky, Y., Santanam, U., Cimmino, A., Palamarchuk, A., Efanov, A., Maximov, V., Volinia, S., Alder, H., Liu, C.G., Rassenti, L., Calin, G.A., Hagan, J.P., Kipps, T. & Croce, C.M. (2006) Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Research, 66, 11590–11593.
- Rodriguez, A., Griffiths-Jones, S., Ashurst, J.L. & Bradley, A. (2004) Identification of mammalian microRNA host genes and transcription units. Genome Research, 14, 1902–1910.
- Roh, T.Y., Cuddapah, S. & Zhao, K. (2005) Active chromatin domains are defined by acetylation islands revealed by genome-wide mapping. Genes & Development, 19, 542–552.
- Roh, T.Y., Wei, G., Farrell, C.M. & Zhao, K. (2007) Genome-wide prediction of conserved and nonconserved enhancers by histone acetylation patterns. Genome Research, 17, 74–81.
- Roman-Gomez, J., Agirre, X., Jiménez-Velasco, A., Arqueros, V., Vilas-Zornoza, A., Rodriguez-Otero, P., Martin-Subero, I., Garate, L., Cordeu, L., San José-Eneriz, E., Martin, V., Antonio Castillejo, J., Bandrés, E., José Calasanz, M., Siebert, R., Heiniger, A., Torres, A. & Prosper, F. (2009) Epigenetic regulation of microRNAs in acute lymphoblastic leukemia. Journal of Clinical Oncology, 27, 1316–1322.
- Saito, Y., Liang, G., Egger, G., Friedman, J.M., Chuang, J.C., Coetzee, G.A. & Jones, P.A. (2006) Specific activation of microRNA-127 with ownregulation of the protooncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell, 9, 435–443.
- Sampson, V.B., Rong, N.H., Han, J., Yang, Q., Aris, V., Soteropoulos, P., Petrelli, N.J., Dunn, S.P. & Krueger, L.J. (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Research, 67, 9762–9770.
- Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B.E., Bergman, Y., Simon, I. & Cedar, H. (2007) Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature Genetics, 39, 232–236.
- Scuto, A., Kirschbaum, M., Kowolik, C., Kretzner, L., Juhasz, A., Atadja, P., Pullarkat, V., Bhatia, R., Forman, S., Yen, Y. & Jove, R. (2008) The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. Blood, 111, 5093–5100.
- Takai, D. & Jones, P.A. (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proceedings of the National Academy of Sciences of the United States of America, 99, 3740–3745.
- Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H., Harano, T., Yatabe, Y., Nagino, M., Nimura, Y., Mitsudomi, T. & Takahashi, T. (2004) Reduced expression of the let-7 in human lung cancers in association with shortened postoperative survival. Cancer Research, 64, 3753–3756.
- Tam, W. & Dahlberg, J.E. (2006) miR-155/BIC as an oncogenic microRNA. Genes, Chromosomes and Cancer, 45, 211–212.
- Taylor, K.H., Pena-Hernandez, K.E., Davis, J.W., Arthur, G.L., Duff, D.J., Shi, H., Rahmatpanah, F.B., Sjahputera, O. & Caldwell, C.W. (2007) Large-scale CpG methylation analysis identifies novel candidate genes and reveals methylation hotspots in acute lymphoblastic leukemia. Cancer Research, 67, 2617–2625.
- Viré, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.M., Bollen, M., Esteller, M., Di Croce, L., De Launoit, Y. & Fuks, F. (2006) The Polycomb group protein EZH2 directly controls DNA methylation. Nature, 439, 871–874.
- Volinia, S., Calin, G.A., Liu, C.G., Ambs, S., Cimmino, A., Petrocca, F., Visone., R., Iorio, M., Roldo, C., Ferracin, M., Prueitt, R.L., Yanaihara, N., Lanza, G., Scarpa, A., Vecchione, A., Negrini, M., Harris, C.C. & Croce, C.M. (2006) 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, 103, 2257–2261.
- Voorhoeve, P.M., Le Sage, C., Schrier, M., Gillis, A.J., Stoop, H., Nagel, R., Liu, Y.P., Van Duijse, J., Drost, J., Griekspoor, A., Zlotorynski, E., Yabuta, N., De Vita, G., Nojima, H., Looijenga, L.H. & Agami, R. (2006) A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell, 124, 1169–1181.
- Wang, Y., Fischle, W., Cheung, W., Jacobs, S., Khorasanizadeh, S. & Allis, C.D. (2004) Beyond the double helix: writing and reading the histone code. Novartis Foundation Symposium, 259, 3–17.
- Xiong, Z. & Laird, P.W. (1997) COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Research, 25, 2532–2534.
- Yu, J., Wang, F., Yang, G.H., Wang, F.L., Ma, Y.N., Du, Z.W. & Zhang, J.W. (2006) Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochemical and Biophysical Research Communications, 349, 59–68.
Citing Literature
