Cited by 333

Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors

Lee, Eun Joo, Baek, Myungwon, Gusev, Yuriy, Brackett, Daniel J., Nuovo, Gerard J., Schmittgen, Thomas D.·2008·RNA

Abstract

Very little is known regarding regulation of microRNA (miRNA) biogenesis in normal tissues, tumors, and cell lines. Here, we profiled the expression of 225 precursor and mature miRNAs using real-time PCR and compared the expression levels to determine the processing patterns. RNA from 22 different human tissues, 37 human cancer cell lines, and 16 pancreas and liver tissues/tumors was profiled. The relationship between precursor and mature miRNA expression fell into the following four categories: (1) a direct correlation exists between the precursor and mature miRNA expression in all cells/tissues studied; (2) direct correlation of the precursor and mature miRNA exists, yet the expression is restricted to specific cell lines or tissues; (3) there is detectable expression of mature miRNA in certain cells and tissues while the precursor is expressed in all or most cells/tissues; or (4) both precursor and mature miRNA are not expressed. Pearson correlation between the precursor and mature miRNA expression was closer to one for the tissues but was closer to zero for the cell lines, suggesting that processing of precursor miRNAs is reduced in cancer cell lines. By using Northern blotting, we show that many of these miRNAs (e.g., miR-31, miR-105 and miR-128a) are processed to the precursor, but in situ hybridization analysis demonstrates that these miRNA precursors are retained in the nucleus. We provide a database of the levels of precursor and mature miRNA in a variety of cell types. Our data demonstrate that a large number of miRNAs are transcribed but are not processed to the mature miRNA.

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Research works printed but not linked: 5

  1. 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., et al. 2005. Real-time quantification of micro- RNAs by stem-loop RT-PCR. Nucleic Acids Res. 33: e179. doi: 10.1093/nar/gni178. · DOI
  2. Griffiths-Jones, S. 2004. The microRNA registry. Nucleic Acids Res. 32: D109-D111. doi: 10.1093/nar/gkh023. · DOI
  3. Jiang, J., Lee, E.J., Gusev, Y., and Schmittgen, T.D. 2005. Real- time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res. 33: 5394-5403. doi: 10.1093/ nar/gki863. · DOI
  4. Jiang, J., Gusev, Y., Aderca, I., Mettler, T.A., Nagorney, D.M., Brackett, D.J., Roberts, L.R., and Schmittgen, T.D. 2007. micro- RNA expression in hepatocellular carcinoma is associated with hepatitis infection, cirrhosis and patient's survival. Clin Cancer Res. (in press).
  5. Schmittgen, T.D., Jiang, J., Liu, Q., and Yang, L. 2004. A high- throughput method to monitor the expression of microRNA precursors. Nucleic Acids Res. 32: E43. doi: 10.1093/nar/gnh040. · DOI

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Authors
Lee, E. J., Baek, M., Gusev, Y., Brackett, D. J., Nuovo, G. J., & Schmittgen, T. D.
Venue
RNA
Published
2007-11-19
Volume
14
Issue
1
Pages
35-42
ISSN
  • 1355-8382
  • 1469-9001
Cited by
333
References
2
Language
en

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