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. Histone deacetylation directs dna methylation in survivin gene silencing. 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. Simultaneous gene silencing of bcl2, xiap and survivin resensitizes pancreatic cancer cells towards apoptosis. 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. Therefore, silencing the survivin gene is an essential requirement of endogenous pten tumor suppression. Genesilencing effects of antisurvivin sirna delivered by rgdvfunctionalized nanodiamond carrier in the breast carcinoma cell line mcf7. Pdf silencing of survivin gene by small interfering rnas.
Silencing of antiapoptotic survivin gene by multiple. Histone deacetylation directs dna methylation in survivin. Targeted gene silencing in vivo by platelet membranecoated. Down regulation of survivin gene and up regulation of p53. Rna interference rnai by small interfering rna sirna can be used to reduce target gene expression in a sequence specific manner by. 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. In this study, caspase2 was inhibited by mir8073 overexpression. Silencing of survivin gene by sirnas causes cell proliferation decline and apoptosis induction in prostate cancer cells.
Proliferation inhibition and apoptosis promotion by dual. Original article effect of survivin on tumor growth of colorectal cancer. Survivin gene expression in npc generally increased. Induction function of sirnamediated survivin gene silencing. Rna shrna is a sequence of rna that makes a tight hairpin turn that can be used to silence target gene expression via rnai. Full text genesilencing effects of antisurvivin sirna delivered by. 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. Survivin also known as birc5 is an evolutionarily conserved eukaryotic protein that is essential for cell division and can inhibit cell death.
Effect of survivinsirnamediated gene silencing on survivin. Casp2 caspase2 is reported to mediate tumor suppression as an initiator of survivin gene silencing 22. Figure 1 synergy of knockdown of bcl2 and survivin. 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. Effects of afp gene silencing on survivin 3185 genetics and molecular research 1 2. That is, a gene which would be expressed turned on under normal circumstances is switched off by machinery in. Research paper silencing of survivin expression leads to. Survivin silencing as a promising strategy to enhance the. Effects of afp gene silencing on survivin mrna expression. 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.
Full text genesilencing effects of antisurvivin sirna. Intravenous sirna silencing of survivin enhances activity of. 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. Effects and mechanism of downregulation of survivin expression by. We previously found that intraperitoneal administration of sirna reversed chemotherapy induced survivin expression in pancreatic xenograft tumors. Silencing stathmin gene expression by survivin promoterdriven. Dual silencing of bcl2 and survivin exhibited a synergistic effect, leading to more cell death than knocking down bcl2 and survivin alone. Gene silencing can occur during either transcription or translation and is often used in research. Silencing of survivin gene by small interfering rnas. Department of horticultural science, kyungpook national university, daegu 702 701, korea. Silencing of survivin expression was examined in a number of cell lines representing different types of tumors mcf7, a549, hela, and hepg2. Caspase 2mediated tumor suppression involves survivin gene.
Nevertheless, to investigate the effectiveness of the shrna approach in gene silencing, we used both exogenous luciferase gene and endogenous survivin gene as targets. Caspase 2mediated tumor suppression involves survivin. Targeting efficiency of ndconhch 2 2 nhvdgrsurvivinsirna in vivo. 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. 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. In vitro transcription of sirna decreased cne2 survivin gene expression, and different sequences of sirna decrease gene expression in cne2 cells to varying degrees. The gene silencing effect of the dual sirna in human osteosarcoma cells and its effects on cell.
Consistent with this model, the catalytic activity of caspase 2 was required for survivin gene silencing, and differential expression of rip1 or nf. Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. 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. Targeting efficiency of ndconhch 2 2 nhvdgr survivin sirna in vivo. Following transfection of cells with 10nm sirna1, the protein of survivin was determined by western blot.
Endogenous tumor suppression mediated by pten involves survivin gene silencing article pdf available in cancer research 6912. Based on the data from the previous experiments, we hypothesized that survivin knockdown will sensitize prostate cancer cells to growth inhibition by msa. Survivin, also called baculoviral inhibitor of apoptosis repeatcontaining 5 or birc5, is a protein that, in humans, is encoded by the birc5 gene. Therefore, survivin may be a promising target for anticancer therapy 14. Silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase.
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. 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. Nanodiamond nd is a renowned material in nonviral small. Downregulation of survivin in human tumor cell lines.
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. Jose, usa according to the instruction manual, and ana. Dna methylation and histone acetylation are major epigenetic modifications in gene silencing. Endogenous tumor suppression mediated by pten involves. Pdf endogenous tumor suppression mediated by pten involves. Three small interfering rnas were designed according to the sequence of survivin gene and they were transferred into. Rna interference, transcriptional gene silencing, virus induced gene silencing, and micro rnas comprise a series of mechanisms capable of suppressing gene expression in plants. 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. It generally describe the switching off of a gene by a mechanism other than genetic modification. Pdf silencing survivin gene expression promotes apoptosis. In this study, we used a rna interferencebased strategy to inhibit survivin expression in human androgenindependent prostate cancer cells.
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. Normally it is only expressed in actively proliferating cells, but is upregulated in most, if not all cancers. Survivin gene silencing sensitizes prostate cancer cells to. Silencing of survivin gene by small interfering rnas produces. Aug 10, 2010 survivin gene silencing sensitizes prostate cancer cells to growth inhibition by msa. Survivin gene silencing sensitizes prostate cancer cells. The foxo family of forkhead transcription factors functions as potential effectors of pten signaling 7. 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. Pdf survivin gene silencing sensitizes prostate cancer. Review rna interference rnai induced gene silencing. Effects and mechanism of downregulation of survivin expression by rna interference on proliferation and apoptosis of lung cancer cells. Silencing of afp expression in hepg2 cells can effectively inhibit the growth of hepatoma cells and promote apoptosis, which may be useful for reducing intracellular. Dec 11, 2015 gene silencing is a technique that aims to reduce or eliminate the production of a protein from its corresponding gene. Today, biochemists have a wide range of survivin antibody products to choose from, suitable for use in western blot, chromatin immunoprecipitation chip, immunofluor.
The proliferation of osteosarcoma cell line mg63 was inhibited after transfection. Pdf silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase. In this report, we designed survivin promoterdriven sirna eukaryotic expression vector that expressed the small interfering. Genesilencing effects of antisurvivin sirna delivered by rgdv. Pdf histone deacetylation directs dna methylation in. These mechanisms reveal similar biochemical pathways and appear to be related in several levels. Survivin gene silencing sensitizes prostate cancer cells to growth inhibition by msa. We investigated the effects of alphafetoprotein afp gene silencing on survivin expression in hepg2 cells. Transfected sirna3 can effectively inhibit cne2 cell proliferation and induce apoptosis. Being selectively expressed in tumor tissues, survivin is a promising target for the development of anticancer strategies aimed at eliminating.
Here, we report on a platelet cell membranecoated metalorganic framework mof nanodelivery platform for the targeted delivery of sirna in vivo. Survivin as a novel target protein for reducing the. Survivin is a protooncogene biomarker known for its antiapoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3kinase pi3kakt pathway. 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. The epcamdependent targeting was demonstrated by the absence of survivin silencing in epcamnegative hek293t cells. Epcam aptamermediated survivin silencing sensitized cancer.
Rna interference rnai is the sequencespecific silencing of genes. 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. Genesilencing effects of antisurvivin sirna delivered by. A promising approach of hitech plant breeding adnan younis1,2, muhammad irfan siddique3, changkil kim1, kibyung lim1 1. Theres a kit for that the survivin antibody is widely used in apoptosis studies, and as a cellular marker.