Silencing of c-myc gene expression using enzymatically and chemically synthesized siRNAs
Abstract
Small interfering RNAs (siRNA) provide a powerful approach for sequence-specific silencing of gene expression. In the present study we investigated inhibition of c-myc gene expression by siRNAs targeted to the sequence 1452-1470 b. in third exon of c-myc mRNA and to homologous regions in second exons of c-myc (697-715 b.) and N-myc (302-320 b.) mRNAs. siRNAs were prepared enzymatically according to the scheme, including dsDNA-templates preparation using Klenow fragment, separate in vitro transcription of each RNA strand with subsequent hybridization and removal of leader sequences by T1 RNase. Investigation of c-myc gene silencing by siRNAs revealed that enzymatically prepared siRNAs induce stronger inhibition of c-myc expression, than siRNA with the same sequence prepared by chemical synthesis. It was found that down-regulation of c-myc gene expression by investigated siRNAs results in efficient inhibition and even complete arrest of carcinoma cell proliferation, moreover, the extend of growth inhibition correlates with the level of siRNA-mediated reduction of c-myc mRNA.
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Kabilova and colleagues synthesized siRNAs targeting different specific regions of c-Myc mRNA that reduced c-Myc mRNA levels in KB-3-1 human epidermoid carcinoma cells and inhibited cell proliferation.
“In 2006, Kabilova and colleagues synthesized siRNAs, compound (241), targeting different specific regions of the c-Myc mRNA using both enzymatic and chemical methods. Both types of synthesized siRNAs were effective in reducing c-Myc mRNA levels in KB-3-1 human epidermoid carcinoma cells, leading to inhibition of cell proliferation.575”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [575]
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- Authors
- Kabilova, T. O., Vladimirova, A. V., Repkova, M. N., Ven’yaminova, A. G., Chernolovskaya, E. L., & Vlasov, V. V.
- Affiliations
- Russian Academy of Sciences (RU)
- Corresponding author
- Kabilova, T. O.
- Venue
- Molecular Biology
- Publisher
- Pleiades Publishing Ltd
- Published
- 2006-12
- Volume
- 40
- Issue
- 6
- Pages
- 936-944
- ISSN
- 0026-8933 (ISSN-L)
- 1608-3245
- OpenAlex
- W2092449685
- Cited by
- 5
- References
- 31
- Citations by year
- 2025: 1 · 2023: 1 · 2012: 1
- FWCI
- 0.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Russian Foundation for Basic Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- c-Myc, siRNA, gene silencing, siRNA synthesis, chemical synthesis comparison, MYCN, Klenow fragment, mRNA down-regulation
- MeSH terms
- Base Sequence, Humans, Molecular Sequence Data, Gene Expression, Genes, myc, Proto-Oncogene Proteins c-myc, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation
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