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Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif.

Taniguchi M, Fujiwara K, Nakai Y, Ozaki T, Koshikawa N, Toshio K, Kataba M, Oguni A, Matsuda H, Yoshida Y, Tokuhashi Y, Fukuda N, Ueno T, Soma M, Nagase H - FEBS Open Bio (2014)

Bottom Line: Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to the E-box sequence (5'-CACGTG-3'), has been observed in many human tumors.In this study, we have designed 5 pyrrole-imidazole (PI) polyamides recognizing E-box, and found that, among them, Myc-6 significantly suppresses malignant phenotypes of human osteosarcoma MG63 cells both in vitro and in vivo.Collectively, our present findings strongly suggest that Myc-6 exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.

View Article: PubMed Central - PubMed

Affiliation: Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan.

ABSTRACT
Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to the E-box sequence (5'-CACGTG-3'), has been observed in many human tumors. In this study, we have designed 5 pyrrole-imidazole (PI) polyamides recognizing E-box, and found that, among them, Myc-6 significantly suppresses malignant phenotypes of human osteosarcoma MG63 cells both in vitro and in vivo. Intriguingly, knockdown of the putative Myc-6 target MALAT1 encoding long noncoding RNA remarkably impaired cell growth of MG63 cells. Collectively, our present findings strongly suggest that Myc-6 exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.

No MeSH data available.


Related in: MedlinePlus

Tumor-suppressive activity of Myc-6 in vivo. (A) Anchorage-independent growth of MG63 cells. Cells were plated onto soft agar medium containing the indicated concentrations of Myc-6. Three weeks after Myc-6 treatment, number of colonies with a diameter of >100 μM was scored. Differences were considered significant at p < 0.05. ∗p < 0.01. The columns represent means ± SD. (B and C) Immuno-deficient nude mice bearing subcutaneously developed tumors derived from MG63 cells were injected intravenously with or without Myc-6 (6 μg/kg) once a week. At the indicated time periods after the first injection, tumor volume was measured. p < 0.05 was considered statistically significant. ∗p < 0.05; ∗∗p < 0.01 (B). Representative photographs of tumors were taken 4 weeks after Myc-6 injection (C).
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f0015: Tumor-suppressive activity of Myc-6 in vivo. (A) Anchorage-independent growth of MG63 cells. Cells were plated onto soft agar medium containing the indicated concentrations of Myc-6. Three weeks after Myc-6 treatment, number of colonies with a diameter of >100 μM was scored. Differences were considered significant at p < 0.05. ∗p < 0.01. The columns represent means ± SD. (B and C) Immuno-deficient nude mice bearing subcutaneously developed tumors derived from MG63 cells were injected intravenously with or without Myc-6 (6 μg/kg) once a week. At the indicated time periods after the first injection, tumor volume was measured. p < 0.05 was considered statistically significant. ∗p < 0.05; ∗∗p < 0.01 (B). Representative photographs of tumors were taken 4 weeks after Myc-6 injection (C).

Mentions: Considering that Myc-6 has a potential pro-apoptotic activity, it is likely that Myc-6 might exert tumor-suppressive ability in vitro and in vivo. To address this issue, MG63 cells were plated onto soft agar medium containing the indicated concentrations of Myc-6. Three weeks after the treatment, number of colonies with a diameter of > 100 μm was scored. The number of colonies was significantly decreased in response to 5 or 10 μM of Myc-6 as compared to that of control cells (Fig. 3A), suggesting that Myc-6 prohibits anchorage-independent growth of MG63 cells.


Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif.

Taniguchi M, Fujiwara K, Nakai Y, Ozaki T, Koshikawa N, Toshio K, Kataba M, Oguni A, Matsuda H, Yoshida Y, Tokuhashi Y, Fukuda N, Ueno T, Soma M, Nagase H - FEBS Open Bio (2014)

Tumor-suppressive activity of Myc-6 in vivo. (A) Anchorage-independent growth of MG63 cells. Cells were plated onto soft agar medium containing the indicated concentrations of Myc-6. Three weeks after Myc-6 treatment, number of colonies with a diameter of >100 μM was scored. Differences were considered significant at p < 0.05. ∗p < 0.01. The columns represent means ± SD. (B and C) Immuno-deficient nude mice bearing subcutaneously developed tumors derived from MG63 cells were injected intravenously with or without Myc-6 (6 μg/kg) once a week. At the indicated time periods after the first injection, tumor volume was measured. p < 0.05 was considered statistically significant. ∗p < 0.05; ∗∗p < 0.01 (B). Representative photographs of tumors were taken 4 weeks after Myc-6 injection (C).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048845&req=5

f0015: Tumor-suppressive activity of Myc-6 in vivo. (A) Anchorage-independent growth of MG63 cells. Cells were plated onto soft agar medium containing the indicated concentrations of Myc-6. Three weeks after Myc-6 treatment, number of colonies with a diameter of >100 μM was scored. Differences were considered significant at p < 0.05. ∗p < 0.01. The columns represent means ± SD. (B and C) Immuno-deficient nude mice bearing subcutaneously developed tumors derived from MG63 cells were injected intravenously with or without Myc-6 (6 μg/kg) once a week. At the indicated time periods after the first injection, tumor volume was measured. p < 0.05 was considered statistically significant. ∗p < 0.05; ∗∗p < 0.01 (B). Representative photographs of tumors were taken 4 weeks after Myc-6 injection (C).
Mentions: Considering that Myc-6 has a potential pro-apoptotic activity, it is likely that Myc-6 might exert tumor-suppressive ability in vitro and in vivo. To address this issue, MG63 cells were plated onto soft agar medium containing the indicated concentrations of Myc-6. Three weeks after the treatment, number of colonies with a diameter of > 100 μm was scored. The number of colonies was significantly decreased in response to 5 or 10 μM of Myc-6 as compared to that of control cells (Fig. 3A), suggesting that Myc-6 prohibits anchorage-independent growth of MG63 cells.

Bottom Line: Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to the E-box sequence (5'-CACGTG-3'), has been observed in many human tumors.In this study, we have designed 5 pyrrole-imidazole (PI) polyamides recognizing E-box, and found that, among them, Myc-6 significantly suppresses malignant phenotypes of human osteosarcoma MG63 cells both in vitro and in vivo.Collectively, our present findings strongly suggest that Myc-6 exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.

View Article: PubMed Central - PubMed

Affiliation: Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan.

ABSTRACT
Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to the E-box sequence (5'-CACGTG-3'), has been observed in many human tumors. In this study, we have designed 5 pyrrole-imidazole (PI) polyamides recognizing E-box, and found that, among them, Myc-6 significantly suppresses malignant phenotypes of human osteosarcoma MG63 cells both in vitro and in vivo. Intriguingly, knockdown of the putative Myc-6 target MALAT1 encoding long noncoding RNA remarkably impaired cell growth of MG63 cells. Collectively, our present findings strongly suggest that Myc-6 exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.

No MeSH data available.


Related in: MedlinePlus