Stathmin is overexpressed and regulated by mutant p53 in oral squamous cell carcinoma.
Stathmin is overexpressed and regulated by mutant p53 in oral squamous cell carcinoma.
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Stathmin 在口腔鳞状细胞癌中过表达并受突变 p53 调节
DOI：
10.1186/s13046-017-0575-4
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发表时间：
2017-08-14
期刊：
影响因子：
--
通讯作者：
Zhong LP
中科院分区：
文献类型：
--
作者：
Ma HL;Jin SF;Ju WT;Fu Y;Tu YY;Wang LZ;Jiang-Li;Zhang ZY;Zhong LP
背景本研究旨在探讨stathmin在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）中的致癌作用及其调控机制。采用CCK-8法、集落形成法、移行法、流式细胞术、免疫荧光法和异种移植模型检测stathmin的功能。免疫组化分析stathmin与p53表达的相关性。突变型/野生型p53质粒和小干扰RNA用于检查stathmin的调节。采用染色质免疫沉淀法和荧光素酶法检测p53对stathmin的转录激活作用。结果在OSCC患者和细胞系中筛选并证实了stathmin的过表达。沉默stathmin表达可抑制细胞增殖、集落形成和迁移，促进细胞凋亡。在抑制stathmin表达后，多聚ADP核糖聚合酶（PARP）和细胞周期蛋白依赖性激酶1（cdc 2）被激活。在体内也证实了对致瘤性的抑制。突变型p53可转录激活stathmin在HN 6和HN 13细胞中的表达，而在携带野生型p53的HN 30细胞中则无此作用。结论stathmin是一种癌基因，受突变型p53的转录调控，而不受野生型p53的调控。Stathmin可能成为口腔鳞癌抗肿瘤治疗的潜在靶点。
BackgroundThe aim of this study was to investigate the oncogenic function and regulatory mechanism of stathmin in oral squamous cell carcinoma (OSCC).MethodsTwo-dimensional electrophoresis and liquid chromatography-tandem mass chromatography were applied to screen differentiated proteins during carcinogenesis in OSCC. Cell Counting Kit-8 (CCK-8) assays, colony formation, migration, flow cytometry, immunofluorescence and a xenograft model were used to detect the function of stathmin. The correlation between stathmin and p53 expression was analyzed using immunohistochemistry. Mutant/wild type p53 plasmids and small interfering RNA were used to examine the regulation of stathmin. Chromatin immunoprecipitation assays and luciferase assays were performed to detect the transcriptional activation of stathmin by p53.ResultsOverexpression of stathmin was screened and confirmed in OSCC patients and cell lines. Silencing expression of stathmin inhibited proliferation, colony formation and migration and promoted apoptosis. Poly ADP ribose polymerase (PARP) and cyclin-dependent kinase 1 (cdc2) were activated after silencing the expression of stathmin. Suppression of tumorigenicity was also confirmed in vivo. Mutant p53 transcriptionally activated the expression of stathmin in HN6 and HN13 cancer cells, but not in HN30 cells harboring wild type p53.ConclusionsThese results suggest that stathmin acts as an oncogene and is transcriptionally regulated by mutant p53, but not by wild-type p53. Stathmin could be a potential anti-tumor therapeutic target in OSCC.