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SNRPB 通过抑制 p53 表达促进宫颈癌进展。

SNRPB promotes cervical cancer progression through repressing p53 expression.

机构信息

Department of Gynecology and Obstetrics, Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing, 100020, China.

Department of 1st Department Gynecology Oncology, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi, 710061, China.

出版信息

Biomed Pharmacother. 2020 May;125:109948. doi: 10.1016/j.biopha.2020.109948. Epub 2020 Feb 25.

Abstract

Cervical cancer is still a leading cause of tumor death in women across the world. Small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) gene encodes the components of the core spliceosomal machinery, and regulates the development of several types of cancers. However, its function in cervical cancer progression remains unclear. In the study, we found that SNRPB was highly expressed in human cervical cancer tissues and in cervical cancer cell lines. Meanwhile, SNRPB knockdown using shRNA in cervical cancer cells markedly reduced the cell proliferation, migration and invasion. Furthermore, the increased percentage of cells in G2/M phase and apoptotic cell death was detected in cervical cancer cells with SNRPB knockdown, suggesting that SNRPB might contribute to cervical cancer growth. Moreover, we found that SNRPB could directly interact with p53, and the interaction showed an essential role in modulating cervical cancer cell proliferation, migration, invasion and apoptosis. In xenograft model, the knockdown of SNRPB exerted effectively anti-cervical cancer ability characterized by the reduced tumor volume and weight, and a remarkable reduction in KI-67 expression. Improved expression of p53 validated the in vitro findings. Therefore, SNRPB might be a potent therapeutic target in cervical cancer through interacting with p53.

摘要

宫颈癌仍然是全世界女性肿瘤死亡的主要原因。小核核糖核蛋白多肽 B 和 B1(SNRPB)基因编码核心剪接体机器的组成部分,调节多种类型癌症的发展。然而,其在宫颈癌进展中的作用尚不清楚。在研究中,我们发现 SNRPB 在人宫颈癌组织和宫颈癌细胞系中高表达。同时,使用 shRNA 在宫颈癌细胞中敲低 SNRPB 显著降低了细胞增殖、迁移和侵袭。此外,在 SNRPB 敲低的宫颈癌细胞中检测到 G2/M 期细胞和凋亡细胞死亡的百分比增加,表明 SNRPB 可能有助于宫颈癌的生长。此外,我们发现 SNRPB 可以直接与 p53 相互作用,这种相互作用在调节宫颈癌细胞增殖、迁移、侵袭和凋亡中起着重要作用。在异种移植模型中,SNRPB 的敲低表现出有效的抗宫颈癌能力,其特征是肿瘤体积和重量减小,以及 KI-67 表达显著降低。p53 的表达改善验证了体外研究结果。因此,SNRPB 可能通过与 p53 相互作用成为宫颈癌的潜在治疗靶点。

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