组蛋白H3(Ser10)磷酸化在维持肿瘤细胞恶性表型中的作用

doi:10.3969/j.issn.1004-616x.2018.02.001

Abstract

Abstract: OBJECTIVE: To investigate the role and mechanism of histone H3 phosphorylation at Ser10[p-H3(Ser10)] on maintainence of malignancy in tumor cells. METHODS: Hepatic tumor cell lines including HepG2,Bel7402,and SMMC-7721 as well as human liver cell line L02 were used to detect the levels of p-H3(Ser10) based on Western blot analysis. In addition,a histone H3 mutant cell line which contained Ser10 mutated at Ala10 (Bel-H3S10A) was constructed. Soft agar assay was conducted to assess the effect of down-regulation of p-H3(Ser10) on the malignant phenotype of tumor cells. The level of histone H3 phosphorylation at Ser10 and its impact on the expression of α4 were detected by western blotting. Bioinformatics was used to identify the adaptor protein 1 (AP-1) binding site of IGBP1 promoter. The relationship between p-H3(Ser10) and the expression of α4 as well as its effect on the transcriptional level of α4 were determined by double luciferase reporter assay and western blot analysis in the constructed Bel7402 and A549 cells overexpressing AP-1and mutated histone H3. RESULTS: p-H3(Ser10) was over-expressed by 2.61 folds and α4 was increased by 2.0-6.3 folds in HCC cell lines(P < 0.05). Moreover,the level of histone H3 phosphorylation at Ser10 in Bel-H3S10A cells was decreased and formed 30% less colonies in soft agar than the control Bel-Vector cells. Cadmium chloride (CdCl₂) induced expression of p-H3(Ser10) and α4 in a dose-dependent manner(P < 0.05). However,the protein expression of α4 decreased by 47% in A549-AP-1-H3S10A cells compared to that in control cells upon CdCl₂ treatment(P < 0.05). CONCLUSION: p-H3(Ser10) played an important role in maintaining malignancy of tumor cells,perhaps through regulating the expression of α4 by activating transcription factor AP-1.

Key words: p-H3(Ser10), α4, tumor cells, malignancy

CLC Number:

R114

LI Qingye, LIU Xiaoling, WU Xiaonen, GUO Ping, CHEN Wen, CHEN Liping. Histone H3 phosphorylation at Ser10 on maintainence of malignancy in tumor cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(2): 81-86,91.

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Histone H3 phosphorylation at Ser10 on maintainence of malignancy in tumor cells

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