Interfering with Cancer: A Brief Outline of Advances in RNA Interference in Oncology

Rye, Phil D.; Stigbrand, Torgny

doi:10.1159/000081403

Cited by 22 publications

(10 citation statements)

References 58 publications

(27 reference statements)

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“…More importantly, with the effectiveness and relative ease with which dsRNA can be introduced into cells and tissues, RNAi has a significant therapeutic potential for targeting human carcinomas. Therefore, RNAi-mediated gene silencing, as a novel tool to arrest tumor growth and kill cancer cells, may open new avenues in cancer therapy [24][25][26][27] . Malignant tumor cells have the ability to migrate into surrounding tissue and/or distal organs -a phenomenon known as metastasis.…”

Section: Discussionmentioning

confidence: 99%

The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells

Zou

Wang

et al. 2011

Acta Pharmacol Sin

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In addition, the ability of the Med19-RNAi-Lentivirus vector-infected Hep3B cells to form tumors after inoculation into nude mice was determined. Results: Recombinant lentiviral vectors expressing small interfering RNA (siRNA) against Med19 were constructed and were found to efficiently downregulate Med19 mRNA and protein levels in HepG2 and Hep3B cells. Furthermore, the inhibition of Med19 by RNAi dramatically reduced hepatocellular carcinoma cell proliferation, induced cell-cycle arrest in the G 0 /G 1 phase, and suppressed tumor formation. Conclusion: These results provide new evidence of an important role for Med19 in the development of hepatocellular carcinomas, suggesting that lentivirus-mediated RNAi to target Med19 is a potential tool for inhibiting cancer cell proliferation and tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells

Zou

Wang

et al. 2011

Acta Pharmacol Sin

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“…Blockade of these signals may be an effective means of inhibiting breast cancer stem cells and of treating metastatic breast cancer [125][126][127][128] .…”

Section: Cancer Stem Cells and Differentiation Therapymentioning

confidence: 99%

“…RNA interference (RNAi) can be used to inhibit gene expression in vitro and in vivo ; this technique involves an oligonucleotide sequence that targets and degrades complementary messenger RNA (target RNA) in the cell [125] . RNAi was fi rst reported in 1998 for Caenorhabditis elegans [126] , and has become a standard procedure in vitro.…”

Section: Cancer Stem Cells and Differentiation Therapymentioning

confidence: 99%

Cancer Stem Cells and Differentiation Therapy

Sell¹

2006

Tumor Biol

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Cancers arise from stem cells in adult tissues and the cells that make up a cancer reflect the same stem cell → progeny → differentiation progression observed in normal tissues. All adult tissues are made up of lineages of cells consisting of tissue stem cells and their progeny (transit-amplifying cells and terminally differentiated cells); the number of new cells produced in normal tissue lineages roughly equals the number of old cells that die. Cancers result from maturation arrest of this process, resulting in continued proliferation of cells and a failure to differentiate and die. The biological behavior, morphological appearance, and clinical course of a cancer depend on the stage of maturation at which the genetic lesion is activated. This review makes a comparison of cancer cells to embryonic stem cells and to adult tis sue stem cells while addressing two basic questions: (1) Where do cancers come from?, and (2) How do cancers grow? The answers to these questions are critical to the development of approaches to the detection, prevention, and treatment of cancer.

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“…Concerning the technology used in this study to target u-PA mRNA, data obtained clearly show that u-PA RNAi effectively inhibits u-PA target gene expression in the absence of toxicity in mice. The HCC xenograft experimental model presented here, together with HCC orthotopic models [29], could be used to perform experimental gene therapy treatments of human HCC xenografts in different animal models by siRNA u-PA constructs (by plasmid or viral vectors) delivered by different tools [30] .…”

Section: Discussionmentioning

confidence: 99%

RNA Interference against Urokinase in Hepatocellular Carcinoma Xenografts in Nude Mice

et al. 2007

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The serine protease urokinase-type plasminogen activator (u-PA) is overexpressed in hepatocellular carcinoma (HCC) and its expression level is inversely correlated with the patients’ survival. The purpose of this study was to examine the effects of vector-based RNA interference (RNAi) of u-PA on the growth of human HCC xenografts in nude mice in order to investigate the role of u-PA in human HCC. Our results showed that the subcutaneous injection of small interfering RNAs (siRNA) u-PA SKHep1C3 stable transfected cells (pS siRNA u-PA) led to a growth delay in xenograft development, compared to those generated from empty vector; the molecular characterization of nodules (carried out by PCR, RT-PCR and immunohistochemical analysis) revealed the presence of plasmid DNA, the u-PA gene expression knockdown, at both mRNA and protein levels, giving evidence of a long-term and target-specific inhibition by vector-based RNAi 11 weeks after cell inoculation. We further studied the effects of u-PA downmodulation on extracellular matrix (ECM) proteins evaluating the expression and organization of fibronectin (FN; one of the main ECM proteins). Immunohistochemical and immunofluorescence analysis of FN revealed FN fibrils in pS siRNA u-PA xenografts and in pS siRNA u-PA cells, thus identifying the FN fibril organization as a downstream effect of u-PA knockdown in this system.

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Interfering with Cancer: A Brief Outline of Advances in RNA Interference in Oncology

Cited by 22 publications

References 58 publications

The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells

The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells

Cancer Stem Cells and Differentiation Therapy

RNA Interference against Urokinase in Hepatocellular Carcinoma Xenografts in Nude Mice

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