Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells

By P. Scacheri, O. Rozenblatt-Rosen, N. Caplen, Tyra G. Wolfsberg, L. Umayam, Jeffrey C. Lee, C. Hughes, K. S. Shanmugam, Arindam K Bhattacharjee, M. Meyerson and 1 more. Proceedings of the National Academy of Sciences of the United States of America, 2004

636 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9c4b202f06e8253680d26081d7556702adb062a6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. John J. Rossi
2. Peter S. Linsley
3. Gregory J. Hannon
4. A. Jackson
5. C. López‐Otín
6. Janell M. Schelter
7. Lee P. Lim
8. J. Burchard

In Molecular Biology

1. John J. Rossi
2. Peter S. Linsley
3. Gregory J. Hannon
4. A. Jackson
5. David P. Bartel
6. C. López‐Otín
7. Norbert Perrimon
8. Janell M. Schelter

Citations in the corpus

• Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP (2004, background): “Although siRNAs can potentially induce nonspecific effects by mediating off-target gene regulation (Scacheri et al., 2004), collagenolytic activity is restored completely when the MT1-MMP siRNA-treated tumor cells are transfected with a mouse MT1-MMP construct that displays only limited homology…”
• The promises and pitfalls of RNA-interference-based therapeutics (2009, neutral): “With the use of microarrays, it has become increasingly obvious that introducing foreign siRNAs into the cell alters the expression of non-target genes, as well as target gene”
• Molecular mechanisms and potential therapeutical targets in Huntington's disease. (2010, background): “Finally, recent studies have highlighted the potential side effects of siRNAs, such as changes in expression of off-target genes (140, 278, 508), induction of cellular immunoreactive responses (532), or competition of exogenous RNA interference with endogenous, intracellular mRNA silencing systems (”
• Evidence of off-target effects associated with long dsRNAs in Drosophila melanogaster cell-based assays (2006, background): “Studies in mammalian cells, however, have shown that RNAi can lead to the degradation of nontargeted mRNAs that happen to contain a cross-hybridizing region to the small interfering RNA (siRNA) trigge”
• Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. (2006, background): “Microarray profiling experiments have demonstrated siRNA-mediated silencing of numerous unintended (off-target) transcripts (Jackson et al. 2003; Semizarov et al. 2003; Scacheri et al. 2004).”
• p53 Activation by Knockdown Technologies (2007, background): “A recent study reports divergent changes in levels of p53 and p21 in cells subjected to ten different siRNAs targeted to menin [4].”
• Unlocking the potential of the human genome with RNA interference (2004, background): “However, it should be noted that the siRNAs in question were relatively impoten”