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Silencing SATB1 inhibits the malignant phenotype and increases sensitivity of human osteosarcoma U2OS cells to arsenic trioxide.

Zhang H, Su X, Guo L, Zhong L, Li W, Yue Z, Wang X, Mu Y, Li X, Li R, Wang Z - Int J Med Sci (2014)

Bottom Line: In a previous study, we found that the global genome organizer Special AT-rich binding protein 1 (SATB1) is highly expressed in mesenchymal-derived human osteosarcoma U2OS cells and that the knock-down of SATB1 results in the inhibition of cell proliferation.Furthermore, mRNA of ABCC1 and ABCG2 were decreased strikingly after SATB1 silencing.It was concluded that the elevated expression of SATB1 in U2OS cells contributes to maintenance of the malignant phenotype and resistance to chemotherapeutic drugs ATO, suggesting that silencing SATB1 in the cells might improve the effects of arsenic trioxides in the treatment of osteosarcoma in which SATB1 is over-expressed and that ABCC1 and ABCG2 were involved in SATB1 mediated resistance of U2OS cells to ATO.

View Article: PubMed Central - PubMed

Affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.

ABSTRACT
In a previous study, we found that the global genome organizer Special AT-rich binding protein 1 (SATB1) is highly expressed in mesenchymal-derived human osteosarcoma U2OS cells and that the knock-down of SATB1 results in the inhibition of cell proliferation. The present study was aimed at investigating the effect of silencing SATB1 on cell migration, invasion, apoptosis and resistance to the chemotherapeutic drug arsenic trioxide. Cell migration and invasion were detected by wound-healing assays and trans-well invasion assays, respectively. Cell apoptosis was analyzed by an in situ Cell Death Detection POD Kit, based on terminal deoxynucleotydyl transferase mediated dUTP nick-end labeling (TUNEL) staining and mRNAs were analyzed by real time qRT-PCR. We found that cell migration and invasion were inhibited and that the proportion of apoptotic cells and sensitivities to the chemotherapeutic drug arsenic trioxide were enhanced by knockdown of SATB1 in U2OS cells. Furthermore, mRNA of ABCC1 and ABCG2 were decreased strikingly after SATB1 silencing. It was concluded that the elevated expression of SATB1 in U2OS cells contributes to maintenance of the malignant phenotype and resistance to chemotherapeutic drugs ATO, suggesting that silencing SATB1 in the cells might improve the effects of arsenic trioxides in the treatment of osteosarcoma in which SATB1 is over-expressed and that ABCC1 and ABCG2 were involved in SATB1 mediated resistance of U2OS cells to ATO.

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SATB1 Silencing decreased the cell migration. The cell migration assay and statistical analysis were carried out as described in the Materials and Methods. (A): A representative microscopic photograph of the cell migration. (B): Statistical results of cell migration. The data are expressed as the mean ± SD, N=9, *P < 0.05, versus non-silenced (Control-shRNA cells).
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Figure 1: SATB1 Silencing decreased the cell migration. The cell migration assay and statistical analysis were carried out as described in the Materials and Methods. (A): A representative microscopic photograph of the cell migration. (B): Statistical results of cell migration. The data are expressed as the mean ± SD, N=9, *P < 0.05, versus non-silenced (Control-shRNA cells).

Mentions: To explore the role of highly expressed SATB1 in maintaining the migratory and invasive traits of the cells, we examined whether knockdown of SATB1 in U2OS cells reduced their migratory and invasive traits using a monolayer wound-healing assay and a Matrigel based Boyden chamber invasion assay. Fig. 1A shows a representative photograph of cell migration and Fig. 1B shows a statistical analysis of the effects of silencing SATB1 on the migration. The percentage of relative migration distance in the two cell clones (SATB1-shRNA1 and SATB1-shRNA3) whose SATB1 had been silenced 23 were 34±4.7 and 29±3.3 respectively, when compared with the percentage of relative migration distance in parent (U2OS: 52±8.5 and transfection control (control-shRNA: 54±6.6). The data indicate that silencing SATB1 decreased the cell migration, suggesting increased expression of SATB1 in U2OS contributes to the elevated migration of these cells. Fig. 2A shows a representative photograph of the cell invasion and Fig. 2B shows the statistical analysis of the effects of silencing SATB1 on cell invasion. Numbers of invasive cells in the two cell clones (SATB1-shRNA1 and SATB1-shRNA3) whose SATB1 had been silenced were 197±15.0 and 182±12.4 respectively, when compared with numbers of invasive cells in parent (U2OS: 410±21.1) and transfection control (control-shRNA: 422±21.1). The data indicate that silencing SATB1 decreased the cell invasion, suggesting that high expression of SATB1 in U2OS contributes to the elevated cell invasion.


Silencing SATB1 inhibits the malignant phenotype and increases sensitivity of human osteosarcoma U2OS cells to arsenic trioxide.

Zhang H, Su X, Guo L, Zhong L, Li W, Yue Z, Wang X, Mu Y, Li X, Li R, Wang Z - Int J Med Sci (2014)

SATB1 Silencing decreased the cell migration. The cell migration assay and statistical analysis were carried out as described in the Materials and Methods. (A): A representative microscopic photograph of the cell migration. (B): Statistical results of cell migration. The data are expressed as the mean ± SD, N=9, *P < 0.05, versus non-silenced (Control-shRNA cells).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4196128&req=5

Figure 1: SATB1 Silencing decreased the cell migration. The cell migration assay and statistical analysis were carried out as described in the Materials and Methods. (A): A representative microscopic photograph of the cell migration. (B): Statistical results of cell migration. The data are expressed as the mean ± SD, N=9, *P < 0.05, versus non-silenced (Control-shRNA cells).
Mentions: To explore the role of highly expressed SATB1 in maintaining the migratory and invasive traits of the cells, we examined whether knockdown of SATB1 in U2OS cells reduced their migratory and invasive traits using a monolayer wound-healing assay and a Matrigel based Boyden chamber invasion assay. Fig. 1A shows a representative photograph of cell migration and Fig. 1B shows a statistical analysis of the effects of silencing SATB1 on the migration. The percentage of relative migration distance in the two cell clones (SATB1-shRNA1 and SATB1-shRNA3) whose SATB1 had been silenced 23 were 34±4.7 and 29±3.3 respectively, when compared with the percentage of relative migration distance in parent (U2OS: 52±8.5 and transfection control (control-shRNA: 54±6.6). The data indicate that silencing SATB1 decreased the cell migration, suggesting increased expression of SATB1 in U2OS contributes to the elevated migration of these cells. Fig. 2A shows a representative photograph of the cell invasion and Fig. 2B shows the statistical analysis of the effects of silencing SATB1 on cell invasion. Numbers of invasive cells in the two cell clones (SATB1-shRNA1 and SATB1-shRNA3) whose SATB1 had been silenced were 197±15.0 and 182±12.4 respectively, when compared with numbers of invasive cells in parent (U2OS: 410±21.1) and transfection control (control-shRNA: 422±21.1). The data indicate that silencing SATB1 decreased the cell invasion, suggesting that high expression of SATB1 in U2OS contributes to the elevated cell invasion.

Bottom Line: In a previous study, we found that the global genome organizer Special AT-rich binding protein 1 (SATB1) is highly expressed in mesenchymal-derived human osteosarcoma U2OS cells and that the knock-down of SATB1 results in the inhibition of cell proliferation.Furthermore, mRNA of ABCC1 and ABCG2 were decreased strikingly after SATB1 silencing.It was concluded that the elevated expression of SATB1 in U2OS cells contributes to maintenance of the malignant phenotype and resistance to chemotherapeutic drugs ATO, suggesting that silencing SATB1 in the cells might improve the effects of arsenic trioxides in the treatment of osteosarcoma in which SATB1 is over-expressed and that ABCC1 and ABCG2 were involved in SATB1 mediated resistance of U2OS cells to ATO.

View Article: PubMed Central - PubMed

Affiliation: 1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China.

ABSTRACT
In a previous study, we found that the global genome organizer Special AT-rich binding protein 1 (SATB1) is highly expressed in mesenchymal-derived human osteosarcoma U2OS cells and that the knock-down of SATB1 results in the inhibition of cell proliferation. The present study was aimed at investigating the effect of silencing SATB1 on cell migration, invasion, apoptosis and resistance to the chemotherapeutic drug arsenic trioxide. Cell migration and invasion were detected by wound-healing assays and trans-well invasion assays, respectively. Cell apoptosis was analyzed by an in situ Cell Death Detection POD Kit, based on terminal deoxynucleotydyl transferase mediated dUTP nick-end labeling (TUNEL) staining and mRNAs were analyzed by real time qRT-PCR. We found that cell migration and invasion were inhibited and that the proportion of apoptotic cells and sensitivities to the chemotherapeutic drug arsenic trioxide were enhanced by knockdown of SATB1 in U2OS cells. Furthermore, mRNA of ABCC1 and ABCG2 were decreased strikingly after SATB1 silencing. It was concluded that the elevated expression of SATB1 in U2OS cells contributes to maintenance of the malignant phenotype and resistance to chemotherapeutic drugs ATO, suggesting that silencing SATB1 in the cells might improve the effects of arsenic trioxides in the treatment of osteosarcoma in which SATB1 is over-expressed and that ABCC1 and ABCG2 were involved in SATB1 mediated resistance of U2OS cells to ATO.

Show MeSH
Related in: MedlinePlus