Inhibition of cell proliferation in HCC-9204 hepatoma cells by a c-myc specific ribozyme

Cheng, Jin Q.; Luo, Jin-Yan; Zhang, Xueyong; Hu, Jialu; Hui, Hongxiang; Wang, Chengji; Stern, Arnold

doi:10.1038/sj.cgt.7700127

Cited by 17 publications

(8 citation statements)

References 27 publications

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“…The reduction of hOGG1 mRNA and protein level in A549-R cell line by our ribozyme was 61.5% and 55.1%, respectively. Because the hammer head ribozyme gene knockdown technique usually can reduce the expression of a specific gene by 30-90% in somatic cells depending on the gene and cell type [Leopold et al, 1995;Wiechen et al, 1998;Cheng et al, 2000;Funato et al, 2000;Kamochi et al, 2002], this indicates that our hOGG1 knockdown efficiency was comparable with that from the other studies. The MTT assay can reflect the activity of succinate dehydrogenase.…”

Section: Discussionsupporting

confidence: 66%

Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells

Che

Zhang

2008

Environ and Mol Mutagen

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Cooking oil fumes (COFs) have been implicated as an important nonsmoking risk factor of lung cancer in Chinese women. However, the molecular mechanism of COFs-induced carcinogenicity remains unknown. To understand the molecular basis underlying COFs-induced cytotoxicity and genotoxicity as well as the roles of hOGG1 in the repair of COFs-induced DNA damage, a human lung cancer cell line with hOGG1 deficiency, A549-R was established by using a ribozyme gene targeting technique that specifically knockdowned hOGG1 in A549 lung adenocarcinoma cells. MTT and comet assays were employed to examine cell viability and DNA damage/repair, respectively, in A549-R and A549 cell lines treated with COF condensate (COFC). RT-PCR and Western blot results showed that the expression of hOGG1 in A549-R cell line was significantly decreased compared with that in A549 cell line. The concentration of COFC that inhibited cell growth by 50% (the IC50) in the A549-R cell line was much lower than that in the A549 cell line, and more COFC-induced DNA damage was detected in the A549-R cell line. The time course study of DNA repair demonstrated delayed repair kinetics in the A549-R cell line, suggesting a decreased cellular damage repair capacity. Our results showed that hOGG1 deficiency enhanced cellular sensitivity to DNA damage caused by COFC. The results further indicate that hOGG1 plays an important role in repairing COF-induced DNA damage. Our study suggests that COFs may lead to DNA damage that is subjected to hOGG1-mediated repair pathways, and oxidative DNA damage may be involved in COF-induced carcinogenesis.

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Section: Discussionsupporting

confidence: 66%

Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells

Che

Zhang

2008

Environ and Mol Mutagen

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“…Previous studies have shown that c-myc is barely expressed in normal liver tissue (Voravud et al, 1989). By contrast, c-myc has been found overexpressed in most of the hepatoma cell lines and its repression by ribozyme or antisense therapy induces differentiation and growth inhibition of these cells (Farshid and Tabor, 1992;Ebinuma et al, 1999;Cheng et al, 2000). Also, in vivo studies have shown that c-myc expression may gradually increase from normal liver to chronic hepatitis, cirrhosis and HCC (Himeno et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Long-term high-dose interferon-α therapy delays Hepadnavirus-related hepatocarcinogenesis in X/myc transgenic mice

et al. 2003

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The role of interferon-a (IFN-a) remains unclear in prevention of virus-induced hepatocellular carcinoma in humans. We have investigated it herewith in the X/myc transgenic mouse model of Hepadnavirus-related hepatocarcinogenesis because of upregulation of c-myc oncogene in the liver. We have demonstrated that IFN-a can downregulate dose-dependently hepatocyte proliferation and c-myc overexpression at early premalignant stages, while it does not affect either hepatocyte apoptosis or telomerase activity at these steps. However, continuous and long-term administration of IFN-a dose-dependently delays tumor onset in dysplastic livers and increases overall survival of animals, more efficiently whether started before the onset of dysplasia. The present study therefore highlights that early preventive administration of IFN-a can slow down evolution towards hepatocellular carcinoma via repression of c-myc and hepatocyte proliferation at premalignant steps in experimental cmyc-induced hepatocarcinogenesis. However, the transient effect observed in this study emphasizes a need to clarify the possible mechanisms of acquired resistance and subsequent therapeutic escape. Our experimental model may be a pertinent tool to explore antioncogenic properties of IFN-a in human cirrhotic livers showing c-myc upregulation.

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“…C-myc is frequently over-expressed in tumors with poor prognosis. The ribozyme-mediated down-regulation of myc was recently shown to be very effective in tumors displaying high myc levels and high proliferating activity [Cheng J. et al (2000)]. …”

Section: Neoplastic Pathologiesmentioning

confidence: 99%

Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes

Citti¹,

Rainaldi²

2005

CGT

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Ribozymes are RNA molecules that have the ability to catalyse the cleavage and formation of covalent bonds in RNA strands at specific sites. The "hammerhead" motif, approximately 30-nucleotide long, is the smallest endonucleolytic cis-acting ribozyme structure found in natural circular RNAs of some plant viroids. Hammerhead ribozymes became appealing when it was shown that it is possible to produce trans-acting ribozymes directed against RNA sequences of interest. Since then, gene-tailored ribozymes have been designed, produced and given to cells to knock down the expression of specific genes. At present, this technology has advanced so much that many hammerhead ribozymes are being used in clinical trials. With this work we would provide some guidelines to design efficient trans-acting hammerhead ribozymes as well as review the recent results obtained with them as gene therapy tools.

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Inhibition of cell proliferation in HCC-9204 hepatoma cells by a c-myc specific ribozyme

Cited by 17 publications

References 27 publications

Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells

Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells

Long-term high-dose interferon-α therapy delays Hepadnavirus-related hepatocarcinogenesis in X/myc transgenic mice

Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes

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