Determinants of interferon-stimulated gene induction by RNAi vectors

Pébernard, Stéphanie; Iggo, Richard

doi:10.1111/j.1432-0436.2004.07202001.x

Cited by 151 publications

(97 citation statements)

References 27 publications

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“…Treatment with siRXFP1s in this experiment did not induce classic interferon target gene 2 0 5 0 -oligoadenylate synthetase, OSA1, suggesting that the delivery of siRNA complexes did not trigger a substantial type I interferon response under these conditions (Bridge et al 2003, Sledz et al 2003, Pebernard & Iggo 2004. There was no difference in the expression of OSA1 gene between the control and experimental group at RNA level based on results of qRT-PCR analysis (data not shown).…”

Section: Effect Of Sirxfp1 On In Vivo Growth Of Lncap Xenograftsmentioning

confidence: 68%

“…This may suggest the intriguing possibility of an active role of RLN signaling in modulating host cell-tumor cell interactions resulting in specific responses, including tumor progression and tumor angiogenesis. It was shown previously that the short hairpin RNAs (shRNAs) or siRNAs may induce an interferon response in transfected cells (Bridge et al 2003, Sledz et al 2003, Pebernard & Iggo 2004. To exclude such nonspecific effects, the expression level of classical interferon target gene OSA1 was measured in cells transfected with siRNA and in tumors treated with siNC/siRXFP1-CNNP complexes.…”

Section: Discussionmentioning

confidence: 99%

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Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Feng

Agoulnik

Truong

et al. 2010

Endocrine-Related Cancer

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Relaxin (RLN) is a small peptide hormone expressed in several cancers of reproductive and endocrine organs. Increased expression of RLN in prostate cancer correlates with aggressive cancer. RLN G-protein-coupled receptor (RLN family peptide receptor 1, RXFP1) is expressed in both androgen receptor (AR)-positive and -negative prostate cancers as well as in prostate cancer cell lines. RLN behaves as a cell growth factor and increases invasiveness and proliferation of cancer cells in vitro and in vivo. The objective of this study is to determine whether downregulation of RXFP1 expression using small interfering RNA (siRNA) reduces cancer growth and metastasis in a xenograft model of prostate cancer. We used two well-characterized prostate adenocarcinoma cell lines, AR-positive LNCaP cells and AR-negative PC3 cells. The tumors were established in nude male mice by s.c. injections. Intratumoral injections of siRNAs loaded on biodegradable chitosan nanoparticles led to a downregulation of RXFP1 receptor expression and a dramatic reduction in tumor growth. In LNCaP tumors, the siRNA treatment led to an extensive necrosis. In PC3 xenografts treated with siRNA against RXFP1, the smaller tumor size was associated with the decreased cell proliferation and increased apoptosis. The downregulation of RXFP1 resulted in significant decrease in metastasis rate in PC3 tumors. Global transcriptional profiling of PC3 cells treated with RXFP1 siRNA revealed genes with significantly altered expression profiles previously shown to promote tumorigenesis, including the downregulation of MCAM, MUC1, ANGPTL4, GPI, and TSPAN8. Thus, the suppression of RLN/RXFP1 may have potential therapeutic benefits in prostate cancer.

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Section: Effect Of Sirxfp1 On In Vivo Growth Of Lncap Xenograftsmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Feng

Agoulnik

Truong

et al. 2010

Endocrine-Related Cancer

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“…AgoshRNAs may have additional benefits as smaller hairpins than regular shRNAs. AgoshRNAs may exhibit a better safety profile concerning activation of the dsRNA-induced protein kinase R and interferon pathways (Pebernard and Iggo 2004). Because AgoshRNAs do not mature via Dicer, they will not compete with this miRNA biogenesis process, and AgoshRNAs seem attractive molecules to silence target genes in Dicer-deficient cells, e.g., monocytes that lack Dicer expression (Coley et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Probing the shRNA characteristics that hinder Dicer recognition and consequently allow Ago-mediated processing and AgoshRNA activity

Herrera-Carrillo

Harwig

Liu

et al. 2014

RNA

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Recent evidence indicates the presence of alternative pathways for microRNA (miRNA) and short hairpin (shRNA) processing. Specifically, some of these molecules are refractory to Dicer-mediated processing, which allows alternative processing routes via the Ago2 endonuclease. The resulting RNA molecules differ in size and sequence and will thus trigger the silencing of different target RNAs. It is, therefore, important to understand these processing routes in mechanistic detail such that one can design exclusive RNA reagents for a specific processing route. The exact sh/miRNA properties that determine this routing toward Dicer or Ago2 are incompletely understood. The size of the base-paired stem seems an important determinant, but other RNA elements may contribute as well. In this study, we document the importance of a weak G-U or U-G base pair at the top of the hairpin stem.

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“…6,7 In addition, cytoplasmic sensors including the RNA-dependent protein kinase can mediate dsRNAtriggered interferon response and in polymerase III driven shRNA expression systems, specific sequences around the transcription start site have been identified, which can also lead to interferon (IFN) induction. 8,9 IFN then binds to cell surface receptors in an auto-or paracrine fashion and confers a more global antiviral state by inducing a complex array of IFN-stimulated genes (ISGs), including RNA-dependent protein kinase and a family of oligo adenylate synthetase (Oas) enzymes. 10 More recently, second generation shRNA constructs have been designed, in which the stem of the endogenously expressed primary microRNA-30 (miRNA-30) was replaced with gene-specific duplexes for different target genes.…”

Section: Introductionmentioning

confidence: 99%

Prevention of interferon-stimulated gene expression using microRNA-designed hairpins

et al. 2008

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Determinants of interferon-stimulated gene induction by RNAi vectors

Cited by 151 publications

References 27 publications

Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

Probing the shRNA characteristics that hinder Dicer recognition and consequently allow Ago-mediated processing and AgoshRNA activity

Prevention of interferon-stimulated gene expression using microRNA-designed hairpins

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