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Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer
Open accessAbstract
Recently, we and others identified the microRNA miR-34a as a target of the tumor suppressor gene product p53. Ectopic miR-34a induces a G(1) cell cycle arrest, senescence and apoptosis. Here we report that miR-34a expression is silenced in several types of cancer due to aberrant CpG methylation of its promoter. 19 out of 24 (79.1%) primary prostate carcinomas displayed CpG methylation of the miR-34a promoter and concomitant loss of miR-34a expression. CpG methylation of the miR-34a promoter was also detected in breast (6/24; 25%), lung (7/24; 29.1%), colon (3/23; 13%), kidney (3/14; 21.4%), bladder (2/6; 33.3%) and pancreatic (3/19; 15.7%) carcinoma cell lines, as well as in melanoma cell lines (19/44; 43.2%) and primary melanoma (20/32 samples; 62.5%). Silencing of miR-34a was dominant over its transactivation by p53 after DNA damage. Re-expression of miR-34a in prostate and pancreas carcinoma cell lines induced senescence and cell cycle arrest at least in part by targeting CDK6. These results show that miR-34a represents a tumor suppressor gene which is inactivated by CpG methylation and subsequent transcriptional silencing in a broad range of tumors.
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A microRNA component of the p53 tumour suppressor network
He, L., He, X., Lim, L. P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., et al. (2007) · Nature · doi:10.1038/nature05939 · Cited by 2,692
Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis
Chang, T.-C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C. J., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.010 · Cited by 2,010
Cited by
The miR-34 family in cancer and apoptosis
Hermeking, H. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.56 · Cited by 1,236
Self-citationDevelopment of a Lung Cancer Therapeutic Based on the Tumor Suppressor MicroRNA-34
Wiggins, J. F., Ruffino, L., Kelnar, K., Omotola, M., Patrawala, L., Brown, D., & Bader, A. G. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0655 · Cited by 677
The role and mechanisms of action of microRNAs in cancer drug resistance
Si, W., Shen, J., Zheng, H., & Fan, W. (2019) · Clinical Epigenetics · doi:10.1186/s13148-018-0587-8 · Cited by 668
Trang, P., Wiggins, J. F., Daige, C. L., Cho, C., Omotola, M., Brown, D., Weidhaas, J. B., Bader, A. G., & Slack, F. J. (2011) · Molecular Therapy · doi:10.1038/mt.2011.48 · Cited by 667
MicroRNA-34a Inhibits Glioblastoma Growth by Targeting Multiple Oncogenes
Li, Y., Guessous, F., Zhang, Y., DiPierro, C., Kefas, B., Johnson, E., Marcinkiewicz, L., Jiang, J., Yang, Y., Schmittgen, T. D., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0529 · Cited by 614
Metadata
- Authors
- Lodygin, D., Tarasov, V., Epanchintsev, A., Berking, C., Knyazeva, T., Körner, H., Knyazev, P., Diebold, J., & Hermeking, H.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2008-08-15
- Volume
- 7
- Issue
- 16
- Pages
- 2591-2600
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2156843318
- Cited by
- 784
- References
- 2
- FWCI
- 17.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Lodygin, D., Tarasov, V., Epanchintsev, A., Berking, C., Knyazeva, T., Körner, H., Knyazev, P., Diebold, J., & Hermeking, H. (2008). Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. https://doi.org/10.4161/cc.7.16.6533
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