Targeted gene silencing in vivo by platelet membranecoated. Figure 1 synergy of knockdown of bcl2 and survivin. Since clinical application of conventional cancer therapies is usually limited by drug resistance and toxic side effects, combination of chemotherapeutic agents with gene therapy appears as an attractive therapeutic strategy to overcome these issues. Chemically synthesized short survivin sirna can effectively inhibit survivin expression and cell proliferation inosteosarcoma cell line mg63 survivin sirna mediated survivin gene silencing may be a useful therapeutic strategy for osteosarcoma. The gene silencing effect of the dual sirna in human osteosarcoma cells and its effects on cell. Downregulation of survivin in human tumor cell lines. In this study, we used a rna interferencebased strategy to inhibit survivin expression in human androgenindependent prostate cancer cells. Effect of survivinsirnamediated gene silencing on survivin. In this study, caspase2 was inhibited by mir8073 overexpression. Effects and mechanism of downregulation of survivin expression by rna interference on proliferation and apoptosis of lung cancer cells. The proliferation of osteosarcoma cell line mg63 was inhibited after transfection. Based on the importance of the angiogenic gene vegf and antiapoptotic gene survivin for tumor formation, we created a onechaindoubletarget sirna for these genes by screening of effective singletarget vegf sirna and survivin sirna sequences.
In vitro transcription of sirna decreased cne2 survivin gene expression, and different sequences of sirna decrease gene expression in cne2 cells to varying degrees. Histone deacetylation directs dna methylation in survivin. It generally describe the switching off of a gene by a mechanism other than genetic modification. Induction function of sirnamediated survivin gene silencing. Therefore, silencing the survivin gene is an essential requirement of endogenous pten tumor suppression.
Dec 11, 2015 gene silencing is a technique that aims to reduce or eliminate the production of a protein from its corresponding gene. Survivin gene silencing sensitizes prostate cancer cells. Survivin is a protooncogene biomarker known for its antiapoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3kinase pi3kakt pathway. Silencing of antiapoptotic survivin gene by multiple.
Survivin gene expression in npc generally increased. Original article effect of survivin on tumor growth of colorectal cancer. We investigated the effects of alphafetoprotein afp gene silencing on survivin expression in hepg2 cells. Simultaneous gene silencing of bcl2, xiap and survivin resensitizes pancreatic cancer cells towards apoptosis. In our previous research, we found that the methylated oligonucleotide surkex complementary to a region of promoter of survivin could induce dna methylation in a sitespecific manner leading to survivin silencing. We previously found that intraperitoneal administration of sirna reversed chemotherapy induced survivin expression in pancreatic xenograft tumors. Survivin also known as birc5 is an evolutionarily conserved eukaryotic protein that is essential for cell division and can inhibit cell death. Nevertheless, to investigate the effectiveness of the shrna approach in gene silencing, we used both exogenous luciferase gene and endogenous survivin gene as targets. Normally it is only expressed in actively proliferating cells, but is upregulated in most, if not all cancers. Gene silencing can occur during either transcription or translation and is often used in research. Today, biochemists have a wide range of survivin antibody products to choose from, suitable for use in western blot, chromatin immunoprecipitation chip, immunofluor. Here, we report on a platelet cell membranecoated metalorganic framework mof nanodelivery platform for the targeted delivery of sirna in vivo. Being selectively expressed in tumor tissues, survivin is a promising target for the development of anticancer strategies aimed at eliminating.
The epcamdependent targeting was demonstrated by the absence of survivin silencing in epcamnegative hek293t cells. Targeting efficiency of ndconhch 2 2 nhvdgrsurvivinsirna in vivo. Pdf survivin gene silencing sensitizes prostate cancer. Down regulation of survivin gene and up regulation of p53. Pdf histone deacetylation directs dna methylation in. Rna interference rnai by small interfering rna sirna can be used to reduce target gene expression in a sequence specific manner by.
Theres a kit for that the survivin antibody is widely used in apoptosis studies, and as a cellular marker. Casp2 caspase2 is reported to mediate tumor suppression as an initiator of survivin gene silencing 22. Silencing of survivin gene by small interfering rnas. Small interfering rna sirna is a powerful tool for gene silencing that has been used for a wide range of biomedical applications, but there are many challenges facing its therapeutic use in vivo. Genesilencing effects of antisurvivin sirna delivered by rgdvfunctionalized nanodiamond carrier in the breast carcinoma cell line mcf7 yanzhao bi, yifan zhang, chunying cui, lulu ren, xueyun jiang school of chemical biology and pharmaceutical sciences, capital medical university, beijing, peoples republic of china abstract. Rna shrna is a sequence of rna that makes a tight hairpin turn that can be used to silence target gene expression via rnai.
Histone deacetylation directs dna methylation in survivin gene silencing. Intravenous sirna silencing of survivin enhances activity of. Rna interference rnai is the sequencespecific silencing of genes. Effects and mechanism of downregulation of survivin expression by. Aug 10, 2010 survivin gene silencing sensitizes prostate cancer cells to growth inhibition by msa. The specificity of the chimeramediated gene silencing was also confirmed through the reversal of survivin knockdown by the introduction of a plasmid expressing an rnairesistant version of survivin cdna. Gene silencing selectivity of ndconhch 2 2 nhvdgr survivin sirna depends on the presence of rgdtargeting peptide,30 and the magnetic sector mass was applied for rgdv detection. Targeting efficiency of ndconhch 2 2 nhvdgr survivin sirna in vivo. The objective of this study is to investigate whether survivin gene silencing in conjunction with selenium treatment could enhance the therapeutic efficacy for prostate cancer and to elucidate the.
Nov 23, 2009 however, it is possible that transcriptional silencing of survivin by various effectors may provide a mandatory requirement for efficient tumor suppression lowe et al. Caspase 2mediated tumor suppression involves survivin. Effects of afp gene silencing on survivin mrna expression. Proliferation inhibition and apoptosis promotion by dual. Full text genesilencing effects of antisurvivin sirna delivered by. Effects of afp gene silencing on survivin 3185 genetics and molecular research 1 2. Genesilencing selectivity of ndconhch 2 2 nhvdgrsurvivinsirna depends on the presence of rgdtargeting peptide,30 and the magnetic sector mass was applied for rgdv detection. Consistent with this model, the catalytic activity of caspase 2 was required for survivin gene silencing, and differential expression of rip1 or nf. Research paper silencing of survivin expression leads to. Free fulltext pdf articles from hundreds of disciplines, all in one place survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition pdf paperity toggle navigation. Survivin gene silencing sensitizes prostate cancer cells to.
Research paper silencing of survivin expression leads to reduced proliferation and cell cycle arrest in cancer cells yuhuan li1, da liu 1, yulin 1zhou, yujing li, jing xie1, robert j. Conditional deletion of pten in the mouse prostate causes deregulated induction of survivin before fullblown transformation in vivo, whereas expression of survivin and pten is inversely correlated in cancer patients. A promising approach of hitech plant breeding adnan younis1,2, muhammad irfan siddique3, changkil kim1, kibyung lim1 1. Alternatively, the sirna approach is likely more effective than the shrna approach, since mammalian cells may have limited ability to process the shrna into sirna. That is, a gene which would be expressed turned on under normal circumstances is switched off by machinery in. Caspase 2mediated tumor suppression involves survivin gene. Survivin silencing as a promising strategy to enhance the. Therefore, survivin may be a promising target for anticancer therapy 14. Jose, usa according to the instruction manual, and ana. Pdf silencing survivin gene expression promotes apoptosis. Being effective and highly specific, rnai probably becomed a new technique in knocking gene down and plays an important role in gene therapy of diseases.
Epcam aptamermediated survivin silencing sensitized cancer. Pdf silencing of survivin gene by small interfering rnas produces supraadditive growth suppression in combination with 17allylamino17demethoxygeldanamycin in human prostate cancer cells francesco paduano and nadia zaffaroni academia. Transfected sirna3 can effectively inhibit cne2 cell proliferation and induce apoptosis. Nanodiamond nd is a renowned material in nonviral small. Silencing stathmin gene expression by survivin promoterdriven. Silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase.
Survivin, also called baculoviral inhibitor of apoptosis repeatcontaining 5 or birc5, is a protein that, in humans, is encoded by the birc5 gene. The foxo family of forkhead transcription factors functions as potential effectors of pten signaling 7. In this report, we designed survivin promoterdriven sirna eukaryotic expression vector that expressed the small interfering. Full text genesilencing effects of antisurvivin sirna. Nov 23, 2009 consistent with this model, the catalytic activity of caspase 2 was required for survivin gene silencing, and differential expression of rip1 or nf. Genesilencing effects of antisurvivin sirna delivered by. Department of horticultural science, kyungpook national university, daegu 702 701, korea. Endogenous tumor suppression mediated by pten involves survivin gene silencing article pdf available in cancer research 6912.
Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Pdf silencing of survivin gene by small interfering rnas. Following transfection of cells with 10nm sirna1, the protein of survivin was determined by western blot. Pdf silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase. Three small interfering rnas were designed according to the sequence of survivin gene and they were transferred into. Silencing of mammalian gene expression by rna interference rnai technology can be achieved using small interfering rna. Dna methylation and histone acetylation are major epigenetic modifications in gene silencing. Silencing of survivin expression leads to reduced proliferation and.
Gene silencing effects of anti survivin sirna delivered by rgdvfunctionalized nanodiamond carrier in the breast carcinoma cell line mcf7. Rna interference, transcriptional gene silencing, virus induced gene silencing, and micro rnas comprise a series of mechanisms capable of suppressing gene expression in plants. Genesilencing effects of antisurvivin sirna delivered by rgdv. Genesilencing effects of antisurvivin sirna delivered by rgdvfunctionalized nanodiamond carrier in the breast carcinoma cell line mcf7. These mechanisms reveal similar biochemical pathways and appear to be related in several levels.
Silencing of survivin gene by sirnas causes cell proliferation decline and apoptosis induction in prostate cancer cells. Survivin gene silencing sensitizes prostate cancer cells to growth inhibition by msa. Research article open access survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition xichun liu1,2, ruijuan gao1,3, yan dong3,4, lifang gao1, yanying zhao1, lijuan. Survivin as a novel target protein for reducing the.
Endogenous tumor suppression mediated by pten involves. Silencing of survivin expression was examined in a number of cell lines representing different types of tumors mcf7, a549, hela, and hepg2. Knockdown of survivin expression by sirnas enhances. Dual silencing of bcl2 and survivin exhibited a synergistic effect, leading to more cell death than knocking down bcl2 and survivin alone.
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