Expressions of poly (ADP-ribose) glycohydrolase (PARG) and membrane type 1 matrix metalloproteinase (MT1-MMP) in colorectal carcinoma

Li, Xian; Guangjie, Duan; Wang, Yalan; Fauzee, Nilufer Jasmine Selimah; Qiao-zhuan, LI

doi:10.1007/s11670-010-0186-5

Cited by 3 publications

(1 citation statement)

References 20 publications

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“…siRNA treatment. Predesigned BRCA2 and PARG SMARTpool siRNA and scrambled siRNA were purchased from metallo-proteinases (known downstream tartgets of NFκB) were also reduced in GLTN-treated cells, 46 suggesting this action of GLTN could also be via inhibition of PARP-1. As both Matrix metallo-proteinases and PARG were upregulated in adenocarcinoma with metastasis and in late tumor stages, these could also be targets for PARG and/or PARP inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells

et al. 2012

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Poly(ADP-ribose) glycohydrolase (PARG), removes poly(ADP-ribose) subunits from proteins that have previously been modified by poly(ADP-ribose) polymerse. This ensures that modification is transient, and it is suggested that removal of poly(ADP-ribose) is essential for some types of DNA repair. Here we show increased γH2AX foci formation and increased homologous recombination when PARG is inhibited. These effects are reduced when replication is inhibited, suggesting that in the absence of PARG activity, replication forks collapse, and homologous recombination is induced for repair. Consistent with this, we show that cells deficient in the homologous recombination protein BRCA2 are sensitive to PARG depletion or inhibition. These data raise the exciting possibility that PARG inhibitors may be used to specifically kill BRCA2 and other homologous recombination-deficient tumors.

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Section: Discussionmentioning

confidence: 99%

Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells

et al. 2012

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Silencing Poly (ADP-Ribose) Glycohydrolase (PARG) Expression Inhibits Growth of Human Colon Cancer Cells In Vitro via PI3K/Akt/NFκ-B Pathway

Fauzee

Qiao-zhuan

Wang

et al. 2011

Pathol. Oncol. Res.

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Poly ADP-ribose polymerase (PARP) which is closely related to Poly ADP-ribose glycohydrolase (PARG) has already been thoroughly investigated in both experimental and clinical cancer trials compared to the latter. Nevertheless, in this experiment the importance of PARG expression was highlighted; whereby it is being silenced via lentivirus vector-mediated short hairpin RNA (shRNA). MTT assay showed that there was an inhibition in human Lovo colon cancer cell growth and flow cytometry demonstrated an increase in the population of cells in G(0)/G(1) phase with a decrease in the S phase in transfected Lovo cells. Furthermore, our results suggested that the effect of silencing PARG leads to the inhibition of PARP expression; related to a decrease in the expression of Nuclear Factor Kappa-B (NFκ-B) with an increase in Akt(473) phosphorylation; suggesting that the Phosphoinositol 3-kinase (PI3K)/Akt/NFκ-B pathway is important for cellular growth and proliferation. Hence, this study emphasizes and converges on the relevance of silencing PARG which inhibits growth of human colonic cancer cells via PI3K/Akt/NFκ-B pathway; as colon carcinoma remains to be amongst one of the commonest cancers throughout the world with high morbidity and mortality rates.

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RNA Interference of PARG Could Inhibit the Metastatic Potency of Colon Carcinoma Cells via PI3-Kinase/Akt Pathway

Qiao-zhuan¹,

Li²,

Wang³

et al. 2012

Cell Physiol Biochem

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Aims: To investigate the role and mechanism of PARG inhibition of metastatic behavior in colonic carcinoma cells. Methods: We examined the effects of PARG protein knockdown by RNA interference on invasion, migration and matrix adhesion of colon carcinoma cell lines in vitro and using a murine in vivo model of liver metastasis. Metastasis related genes were detected using mRNA and protein levels. Moreover, LY294002, an Akt phosphorylation inhibitor, was used to determine whether the suppression of metastatic behavior of colon carcinoma cells was mediated by Akt phosphorylation that was confirmed by EMSA. Pyrrolidine dithiocarbamate (PDTC) was used as a selective NFĸ-B inhibitor to clarify the relationship between PARG, PARP and NF-ĸB. Results: PARG protein was undetectable following specific shRNA transfection; mRNA and protein levels of PARP were significantly decreased. PARG-shRNA cells showed high levels of phosphorylated Akt with decreased expression of NF-ĸB (both total & nuclear), MMP2 and MMP9. However, no additional changes were noted following inhibition of PI3K/Akt pathway by LY294002 in the PARG-shRNA cells; these cells displayed reduced number of liver metastases when characterized in the murine in vivo model. Conclusion: PARG knockdown, concomitant with inhibition of PARP, suppressed the metastatic potency of colon carcinoma cells by activation of PI3K/Akt signaling pathway.

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Expressions of poly (ADP-ribose) glycohydrolase (PARG) and membrane type 1 matrix metalloproteinase (MT1-MMP) in colorectal carcinoma

Cited by 3 publications

References 20 publications

Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells

Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells

Silencing Poly (ADP-Ribose) Glycohydrolase (PARG) Expression Inhibits Growth of Human Colon Cancer Cells In Vitro via PI3K/Akt/NFκ-B Pathway

RNA Interference of PARG Could Inhibit the Metastatic Potency of Colon Carcinoma Cells via PI3-Kinase/Akt Pathway

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