Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018;19(8):604-610.
doi: 10.2174/1389201019666180528084059.

Therapeutic Potential of Small Activating RNAs (saRNAs) in Human Cancers

Sorah Yoon  1 , John J Rossi  1   2
Affiliations
Review

Therapeutic Potential of Small Activating RNAs (saRNAs) in Human Cancers

Sorah Yoon et al. Curr Pharm Biotechnol. 2018.

Abstract

Background: RNA is increasingly recognized as a powerful molecule that can be used to control gene expression. Sophisticated, well-engineered RNA-based regulators are being developed as oligotherapeutics.

Methods: In particular, small activating RNAs (saRNAs) are promising therapeutic options for targeting human diseases. Numerous saRNAs targeting multiple cancers have been developed in preclinical models. One saRNA targeting C/EBPα is currently undergoing clinical trials in liver cancer.

Results and conclusion: In this review, we describe the current working model of the intracellular mechanism of saRNA, discuss the recent progress of saRNA therapeutics in preclinical and clinical trials, and current advances in targeted delivery using aptamers in detail.

Keywords: aptamers; clinic; human cancers; intracellular mechanism; saRNAs; targeted delivery; therapeutics..

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1)
Canonical activating mechanism of saRNAs. A saRNA-loaded AGO2 complex binds at the target promoter and induces the open chromatin structure. The AGO2 recruits the complex of CTR9 and RHA, RNA-induced transcriptional activation (RITA), leading the transcript initiation associating with phosphorylation of RNAP II on Ser2 and H2Bub1.
Fig. (2)
Fig. (2)
Non-canonical activating mechanism of saRNAs. RNAs complementary to a non-coding transcript at the promoter activates gene expression in recruitment of Ago2. This model comes with unresolved questions that require further investigation, as indicated.
Fig. (3)
Fig. (3)
Targeted delivery of saRNAs. Aptamer-conjugated saRNAs are internalized via cancer-specific receptors. The aptamer-saRNAs disassociate in the cytoplasm. The saRNAs are transported into the nucleus, where they induce the upregulation of target genes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Li L.C., Okino S.T., Zhao H., Pookot D., Place R.F., Urakami S., Enokida H., Dahiya R. Small dsRNAs induce transcriptional activation in human cells. Proc. Natl. Acad. Sci. USA. 2006;103(46):17337–17342. - PMC - PubMed
    1. Huang V., Qin Y., Wang J., Wang X., Place R.F., Lin G., Lue T.F., Li L.C. RNAa is conserved in mammalian cells. PLoS One. 2010;5(1):e8848. - PMC - PubMed
    1. Voutila J., Saetrom P., Mintz P., Sun G., Alluin J., Rossi J.J., Habib N.A., Kasahara N. Gene expression profile changes after short-activating RNA-mediated induction of endogenous pluripotency factors in human mesenchymal stem cells. Mol. Ther. Nucleic Acids. 2012;1:e35. - PMC - PubMed
    1. Meng X., Jiang Q., Chang N., Wang X., Liu C., Xiong J., Cao H., Liang Z. Small activating RNA binds to the genomic target site in a seed-region-dependent manner. Nucleic Acids Res. 2016;44(5):2274–2282. - PMC - PubMed
    1. Place R.F., Noonan E.J., Foldes-Papp Z., Li L.C. Defining features and exploring chemical modifications to manipulate RNAa activity. Curr. Pharm. Biotechnol. 2010;11(5):518–526. - PMC - PubMed

Substances