ANG Promotes Proliferation and Invasion of the Cell of Lung Squamous Carcinoma by Directly Up-Regulating HMGA2.
ANG Promotes Proliferation and Invasion of the Cell of Lung Squamous Carcinoma by Directly Up-Regulating HMGA2.
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ANG直接上调HMGA2促进肺鳞癌细胞增殖和侵袭
DOI：
10.7150/jca.14440
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发表时间：
2016
影响因子：
3.9
通讯作者：
Chen HZ
中科院分区：
文献类型：
--
作者：
Xu L;Liao WL;Lu QJ;Li CG;Yuan Y;Xu ZY;Huang SD;Chen HZ
目的：探讨血管生成素（ANG）在肺鳞癌发生发展中的作用机制。方法：收集12例患者的正常组织和癌组织。采用qRT-PCR和western-blot检测ANG在肺鳞癌中的表达。分别采用Cell Counting Kit-8、Transwell迁移小室、Transwell侵袭小室和Annexin V-FITC法分析ANG对SK-MES-1细胞增殖、迁移、侵袭和凋亡的调节作用。利用PCR芯片筛选ANG的潜在靶基因。采用染色质免疫沉淀法和荧光素酶法研究ANG对HMGA 2的直接调控作用。结果：ANG在肺鳞癌组织中表达增高。体外实验结果表明，ANG过表达可促进SK-MES-1细胞的增殖和侵袭能力。HMGA 2是与ANG增殖、迁移和侵袭相关的候选靶基因，其在肺鳞癌组织中的表达水平也明显升高。通过ChIP和荧光素酶测定结果证实ANG对HMGA 2的直接调节。下调HMGA 2可明显减轻ANG对SK-MES-1细胞增殖、迁移和侵袭的抑制作用。结论：结果表明，ANG通过直接上调HMGA 2的表达，促进SQCLC细胞增殖、迁移和侵袭能力。
Objective: To determine the mechanism of Angiogenin(ANG) function involved in the carcinogenesis of lung squamous cell carcinoma. Methods: 12 patients' normal tissue and cancerous tissue were collected. ANG expression in the squamous cell carcinoma of the lung was evaluated by qRT-PCR and western-blot. The regulation of ANG on proliferation, migration, invasion, and apoptosis of SK-MES-1 cells were analyzed by Cell Counting Kit-8, Transwell migration chamber, Transwell invasion chamber, and Annexin V-FITC assay, respectively. PCR array was utilized for screening potential target genes of ANG. Chromatin immunoprecipitation(ChIP) assays and luciferase assay were adopted for investigation of ANG's direct regulation on HMGA2. Results: ANG expression is increased in the squamous cell carcinoma of the lung tissue. In vitro experiments results indicated that overexpression of ANG promotes proliferation and invasion capability of SK-MES-1 cells. The candidate proliferation, migration, and invasion related ANG target gene found was HMGA2, expression levels of which were also enhanced in lung squamous cell carcinoma tissue. The direct regulation of ANG on HMGA2 was verified by ChIP and luciferase assay results. Furthermore, down-regulating HMGA2 significantly alleviated the suppression effects of ANG on proliferation, migration, and invasion of SK-MES-1 cells. Conclusions: Our data illustrated the mechanisms that ANG promoted the cell of SQCLC proliferation, migration, and invasion capacity via directly up-regulating HMGA2.