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血管生成素通过直接上调HMGA2促进肺鳞癌细胞的增殖和侵袭。

ANG Promotes Proliferation and Invasion of the Cell of Lung Squamous Carcinoma by Directly Up-Regulating HMGA2.

作者信息

Xu Li, Liao Wei-Lin, Lu Qi-Jue, Li Chun-Guang, Yuan Yang, Xu Zhi-Yun, Huang Sheng-Dong, Chen He-Zhong

机构信息

Department of Cardiothoracic surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.

出版信息

J Cancer. 2016 Apr 28;7(7):862-71. doi: 10.7150/jca.14440. eCollection 2016.

Abstract

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.

摘要

目的

确定血管生成素(ANG)在肺鳞状细胞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检测肺鳞状细胞癌中ANG的表达。分别通过细胞计数试剂盒-8、Transwell迁移小室、Transwell侵袭小室和Annexin V-FITC检测分析ANG对SK-MES-1细胞增殖、迁移、侵袭和凋亡的调控作用。利用PCR阵列筛选ANG的潜在靶基因。采用染色质免疫沉淀(ChIP)试验和荧光素酶试验研究ANG对HMGA2的直接调控作用。

结果

肺组织鳞状细胞癌中ANG表达增加。体外实验结果表明,ANG过表达促进SK-MES-1细胞的增殖和侵袭能力。发现的与增殖、迁移和侵袭相关的ANG候选靶基因是HMGA2,其在肺鳞状细胞癌组织中的表达水平也升高。ChIP和荧光素酶试验结果证实了ANG对HMGA2的直接调控作用。此外,下调HMGA2可显著减轻ANG对SK-MES-1细胞增殖、迁移和侵袭的抑制作用。

结论

我们的数据阐明了ANG通过直接上调HMGA2促进肺鳞状细胞癌细胞增殖、迁移和侵袭能力的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36f1/4860804/d2985654e4ec/jcav07p0862g001.jpg

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