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SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis.

Zhang J, Jiang H, Shao J, Mao R, Liu J, Ma Y, Fang X, Zhao N, Zheng S, Lin B - BMC Neurol (2014)

Bottom Line: High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1.Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways.Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China. jingzh1985@gmail.com.

ABSTRACT

Background: SOX4 is a transcription factor required for tissue development and differentiation in vertebrates. Overexpression of SOX4 has been reported in many cancers including glioblastoma multiforme (GBM), however, the underlying mechanism of actions has not been studied. In this study, we investigated the role of SOX4 in GBM.

Methods: Kaplan-Meier analysis was performed to assess the association between SOX4 expression levels and survival times in primary GBM samples. Cre/lox P system was used to generate gain or loss of SOX4 in GBM cells, and microarray analysis uncovered the regulation network of SOX4 in GBM cells.

Results: High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1. Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways.

Conclusions: Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.

No MeSH data available.


Related in: MedlinePlus

Microarry analysis of genes regulated by SOX4 in LN229 SOX4 overexpressed cells. (A) Validation of SOX4 regulated gene by Real-time PCR. The relative expression of target gene was normalized to the endogenous control GAPDH. Three replicate PCR were performed and the standard errors of the mean were indicated by error bars. (B) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH/U87_pSFH compare to LN229_con/A172_con/U87_con cells by RT-PCR and Western blotting with anti beta-catenin antibody. (C) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH compare to LN229_con/A172_con by Western blotting with anti phosphor-beta-catenin antibody. (D) Validation of cellular localization of SOX4 increased beta-catenin. Anti-histone H3 antibody was used to normalize the amount of nuclear sample.
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Fig5: Microarry analysis of genes regulated by SOX4 in LN229 SOX4 overexpressed cells. (A) Validation of SOX4 regulated gene by Real-time PCR. The relative expression of target gene was normalized to the endogenous control GAPDH. Three replicate PCR were performed and the standard errors of the mean were indicated by error bars. (B) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH/U87_pSFH compare to LN229_con/A172_con/U87_con cells by RT-PCR and Western blotting with anti beta-catenin antibody. (C) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH compare to LN229_con/A172_con by Western blotting with anti phosphor-beta-catenin antibody. (D) Validation of cellular localization of SOX4 increased beta-catenin. Anti-histone H3 antibody was used to normalize the amount of nuclear sample.

Mentions: To identify genes regulated by SOX4 in GBM cells, we used Affymetrix’s The GeneChip® PrimeView™ Human Gene Expression Array to compare SOX4 overexpression LN229_pSFH and LN229_con cells. We identified 633 genes were changed more than 1.8 fold (Additional file 5: Table S3). The array data was confirmed by doing real-time PCR, and 9 of 10 randomly selected changed genes identified by array was confirmed by RT-PCR (Figure 5A).Figure 5


SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis.

Zhang J, Jiang H, Shao J, Mao R, Liu J, Ma Y, Fang X, Zhao N, Zheng S, Lin B - BMC Neurol (2014)

Microarry analysis of genes regulated by SOX4 in LN229 SOX4 overexpressed cells. (A) Validation of SOX4 regulated gene by Real-time PCR. The relative expression of target gene was normalized to the endogenous control GAPDH. Three replicate PCR were performed and the standard errors of the mean were indicated by error bars. (B) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH/U87_pSFH compare to LN229_con/A172_con/U87_con cells by RT-PCR and Western blotting with anti beta-catenin antibody. (C) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH compare to LN229_con/A172_con by Western blotting with anti phosphor-beta-catenin antibody. (D) Validation of cellular localization of SOX4 increased beta-catenin. Anti-histone H3 antibody was used to normalize the amount of nuclear sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4233052&req=5

Fig5: Microarry analysis of genes regulated by SOX4 in LN229 SOX4 overexpressed cells. (A) Validation of SOX4 regulated gene by Real-time PCR. The relative expression of target gene was normalized to the endogenous control GAPDH. Three replicate PCR were performed and the standard errors of the mean were indicated by error bars. (B) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH/U87_pSFH compare to LN229_con/A172_con/U87_con cells by RT-PCR and Western blotting with anti beta-catenin antibody. (C) Validation of SOX4 increased beta-catenin in LN229_pSFH/A172_pSFH compare to LN229_con/A172_con by Western blotting with anti phosphor-beta-catenin antibody. (D) Validation of cellular localization of SOX4 increased beta-catenin. Anti-histone H3 antibody was used to normalize the amount of nuclear sample.
Mentions: To identify genes regulated by SOX4 in GBM cells, we used Affymetrix’s The GeneChip® PrimeView™ Human Gene Expression Array to compare SOX4 overexpression LN229_pSFH and LN229_con cells. We identified 633 genes were changed more than 1.8 fold (Additional file 5: Table S3). The array data was confirmed by doing real-time PCR, and 9 of 10 randomly selected changed genes identified by array was confirmed by RT-PCR (Figure 5A).Figure 5

Bottom Line: High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1.Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways.Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China. jingzh1985@gmail.com.

ABSTRACT

Background: SOX4 is a transcription factor required for tissue development and differentiation in vertebrates. Overexpression of SOX4 has been reported in many cancers including glioblastoma multiforme (GBM), however, the underlying mechanism of actions has not been studied. In this study, we investigated the role of SOX4 in GBM.

Methods: Kaplan-Meier analysis was performed to assess the association between SOX4 expression levels and survival times in primary GBM samples. Cre/lox P system was used to generate gain or loss of SOX4 in GBM cells, and microarray analysis uncovered the regulation network of SOX4 in GBM cells.

Results: High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1. Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways.

Conclusions: Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.

No MeSH data available.


Related in: MedlinePlus