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Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of neuroblastoma by targeting CTGF and PDGF-β.

Wang M, Liu Y, Zou J, Yang R, Xuan F, Wang Y, Gao N, Cui H - Oncotarget (2015)

Bottom Line: Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells.Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells.Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.

ABSTRACT
Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial event in the pathogenesis of neuroblastoma is to promote proliferation of neuroblasts, which is closely related to poor survival. However, mechanisms for regulation of cell proliferation and tumorigenicity in neuroblastoma are not well understood. Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells. Inhibition of endogenous TAZ attenuated cell proliferation, colony formation and tumor development in neuroblastoma SK-N-AS cell, which could be rescued by re-introduction of TAZ into TAZ-knockdown cells. In addition, we found that overexpressing TAZ-mediated induction of CTGF and PDGF-β expression, cell proliferation and colony formation were inhibited by knocking down CTGF and PDGF-β with siRNA in TAZ-overexpressing cell. Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells. Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

No MeSH data available.


Related in: MedlinePlus

CTGF is a major downstream transcriptional target of TAZTAZ overexpressing BE(2)-C cells were infected with CTGF siRNA. (A) qRT-PCR analysis was performed to determine the expression of CTGF at mRNA levels. Data represent the means ± SD from three independent experiments, *P < 0.05. (B) Western blot analysis was performed to determine the expression of CTGF. GAPDH levels are shown as loading control. (C) Cells were seed into a 96-well plate (1000 cells/well), after which cell proliferation was determined using cell counting kit-8 assay kit. Data represent the means ± SD from three independent experiments (*P < 0.05). (D) Colony formation was examined by soft agar assay. (E) Colony number was counted using counter. The values represent the mean ± SD from three independent experiments (*P < 0.05).
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Figure 7: CTGF is a major downstream transcriptional target of TAZTAZ overexpressing BE(2)-C cells were infected with CTGF siRNA. (A) qRT-PCR analysis was performed to determine the expression of CTGF at mRNA levels. Data represent the means ± SD from three independent experiments, *P < 0.05. (B) Western blot analysis was performed to determine the expression of CTGF. GAPDH levels are shown as loading control. (C) Cells were seed into a 96-well plate (1000 cells/well), after which cell proliferation was determined using cell counting kit-8 assay kit. Data represent the means ± SD from three independent experiments (*P < 0.05). (D) Colony formation was examined by soft agar assay. (E) Colony number was counted using counter. The values represent the mean ± SD from three independent experiments (*P < 0.05).

Mentions: To examine the role of CTGF and PDGF-β in TAZ-induced proliferation and tumorigenesis, we respectively knocked down CTGF and PDGF-β in TAZ overexpressing BE(2)-C cells. Western blot and real time RT-PCR analysis showed that knocking down CTGF in TAZ overexpressing cells with CTGF siRNA decreased the protein and mRNA levels of CTGF in these cells (Figure 7A and 7B). Proliferation of TAZ overexpressing cell was suppressed when CTGF was knocked down by siRNA (Figure 7C). Knockdown of CTGF by siRNA (CTGFsi) in TAZ overexpressing cells also decreased the colony formation compared with vector control cells (Figure 7D and 7E).


Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of neuroblastoma by targeting CTGF and PDGF-β.

Wang M, Liu Y, Zou J, Yang R, Xuan F, Wang Y, Gao N, Cui H - Oncotarget (2015)

CTGF is a major downstream transcriptional target of TAZTAZ overexpressing BE(2)-C cells were infected with CTGF siRNA. (A) qRT-PCR analysis was performed to determine the expression of CTGF at mRNA levels. Data represent the means ± SD from three independent experiments, *P < 0.05. (B) Western blot analysis was performed to determine the expression of CTGF. GAPDH levels are shown as loading control. (C) Cells were seed into a 96-well plate (1000 cells/well), after which cell proliferation was determined using cell counting kit-8 assay kit. Data represent the means ± SD from three independent experiments (*P < 0.05). (D) Colony formation was examined by soft agar assay. (E) Colony number was counted using counter. The values represent the mean ± SD from three independent experiments (*P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4496235&req=5

Figure 7: CTGF is a major downstream transcriptional target of TAZTAZ overexpressing BE(2)-C cells were infected with CTGF siRNA. (A) qRT-PCR analysis was performed to determine the expression of CTGF at mRNA levels. Data represent the means ± SD from three independent experiments, *P < 0.05. (B) Western blot analysis was performed to determine the expression of CTGF. GAPDH levels are shown as loading control. (C) Cells were seed into a 96-well plate (1000 cells/well), after which cell proliferation was determined using cell counting kit-8 assay kit. Data represent the means ± SD from three independent experiments (*P < 0.05). (D) Colony formation was examined by soft agar assay. (E) Colony number was counted using counter. The values represent the mean ± SD from three independent experiments (*P < 0.05).
Mentions: To examine the role of CTGF and PDGF-β in TAZ-induced proliferation and tumorigenesis, we respectively knocked down CTGF and PDGF-β in TAZ overexpressing BE(2)-C cells. Western blot and real time RT-PCR analysis showed that knocking down CTGF in TAZ overexpressing cells with CTGF siRNA decreased the protein and mRNA levels of CTGF in these cells (Figure 7A and 7B). Proliferation of TAZ overexpressing cell was suppressed when CTGF was knocked down by siRNA (Figure 7C). Knockdown of CTGF by siRNA (CTGFsi) in TAZ overexpressing cells also decreased the colony formation compared with vector control cells (Figure 7D and 7E).

Bottom Line: Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells.Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells.Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.

ABSTRACT
Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial event in the pathogenesis of neuroblastoma is to promote proliferation of neuroblasts, which is closely related to poor survival. However, mechanisms for regulation of cell proliferation and tumorigenicity in neuroblastoma are not well understood. Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells. Inhibition of endogenous TAZ attenuated cell proliferation, colony formation and tumor development in neuroblastoma SK-N-AS cell, which could be rescued by re-introduction of TAZ into TAZ-knockdown cells. In addition, we found that overexpressing TAZ-mediated induction of CTGF and PDGF-β expression, cell proliferation and colony formation were inhibited by knocking down CTGF and PDGF-β with siRNA in TAZ-overexpressing cell. Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells. Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

No MeSH data available.


Related in: MedlinePlus