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NUSAP1 通过激活 Hedgehog 信号通路调节基底细胞癌的迁移、侵袭和 DNA 损伤。

NUSAP1 regulates basal cell carcinoma migration, invasion and DNA damage through activation of the Hedgehog signaling pathway.

机构信息

Department of Dermatology, The Second People's Hospital of Chengdu, Chengdu, Sichuan, 610000, China.

出版信息

Physiol Int. 2023 May 17;110(2):160-172. doi: 10.1556/2060.2023.00227. Print 2023 Jun 12.

Abstract

BACKGROUND

Basal cell carcinoma (BCC) is a prevalent cutaneous cancer with an increasing incidence. Nucleolar and spindle associated protein 1 (NUSAP1) is a cell proliferation-related protein that participates in the development of various cancers. However, its role and mechanism in BCC remain elusive.

METHODS

The expression of NUSAP1 was detected by western blot. Gain- and loss-of-function assays were performed through the transfection of overexpression plasmid of NUSAP1 and si NUSAP1 into TE354.T cells. The role and mechanism of action of NUSAP1 in BCC were explored by cell counting kit-8 (CCK-8), colony formation, transwell, flow cytometry and western blot assays.

RESULTS

NUSAP1 was highly expressed in TE354.T cells. Overexpression of NUSAP1 enhanced cell viability, colony forming numbers, numbers of migrated and invasive cells and the relative protein expression of RAD51, but reduced the apoptosis rate and the relative protein expression of γH2AX in TE354.T cells. Inverse results were obtained in these indicators after TE354.T cells were downregulated with NUSAP1. Moreover, the relative expression of proteins involved in the Hedgehog signaling pathway was increased by transfection of the overexpression plasmid of NUSAP1 into TE354.T cells, but decreased by the transfection of si NUSAP1 into TE354.T cells.

CONCLUSION

Both gain- and loss-of-function results revealed that NUSAP1 promoted proliferation, migration and invasion but attenuated apoptosis and DNA damage in BCC, which was involved in the activation of the Hedgehog signaling pathway.

摘要

背景

基底细胞癌(BCC)是一种常见的皮肤癌,发病率呈上升趋势。核仁纺锤体相关蛋白 1(NUSAP1)是一种与细胞增殖相关的蛋白,参与多种癌症的发生。然而,其在 BCC 中的作用和机制尚不清楚。

方法

通过 Western blot 检测 NUSAP1 的表达。通过转染 NUSAP1 过表达质粒和 si NUSAP1 到 TE354.T 细胞中,进行增益和失能实验。通过细胞计数试剂盒-8(CCK-8)、集落形成、Transwell、流式细胞术和 Western blot 实验,探讨 NUSAP1 在 BCC 中的作用和作用机制。

结果

NUSAP1 在 TE354.T 细胞中高表达。过表达 NUSAP1 增强了 TE354.T 细胞的活力、集落形成数量、迁移和侵袭细胞数量以及 RAD51 的相对蛋白表达,但降低了细胞凋亡率和 γH2AX 的相对蛋白表达。下调 NUSAP1 后,这些指标在 TE354.T 细胞中出现相反的结果。此外,转染 NUSAP1 过表达质粒可增加 Hedgehog 信号通路相关蛋白的相对表达,而转染 si NUSAP1 则可降低其表达。

结论

功能增益和功能丧失的结果均表明,NUSAP1 促进了 BCC 的增殖、迁移和侵袭,但减弱了细胞凋亡和 DNA 损伤,这与 Hedgehog 信号通路的激活有关。

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