PSPC1基因敲除促进鼻咽癌细胞放射敏感性、抑制EMT和转移

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-09-15 DOI:10.1016/j.yexcr.2025.114755

Huocong He , Zhengrong Huang , Fuli Wen , Na Ge , Xiandong Lin , Jianru Pan

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引用次数: 0

摘要

目的：旁斑成分1 （PSPC1）在许多癌症中上调，并与患者生存率降低相关。我们之前的研究表明，鼻咽癌（NPC）中PSPC1水平升高与放疗耐药和肿瘤转移呈正相关，这是鼻咽癌治疗的两个主要临床挑战。然而，PSPC1在鼻咽癌细胞放射抵抗和转移中的确切作用尚不清楚。本研究旨在探讨PSPC1影响鼻咽癌放射耐药和转移的分子机制。方法：利用耐辐射的鼻咽癌R743和辐射敏感的CNE2细胞系，研究PSPC1表达对鼻咽癌放疗后存活、细胞周期进展、凋亡、迁移、侵袭和肿瘤生长的影响。采用CRISPR/Cas9基因组编辑技术在R743细胞中产生PSPC1敲除（KO）细胞系，通过pcDNA3.1(+)-PSPC1质粒转染在CNE2细胞中实现PSPC1过表达（ppd -PSPC1）。结果：PSPC1敲除将R743细胞从放射抗性转化为放射敏感性，而PSPC1过表达降低了CNE2细胞的放射敏感性。细胞周期分析显示，PSPC1 KO在辐照后使R743细胞处于G2/M期，而PSPC1过表达使CNE2细胞处于G2/M期。PSPC1 KO增加了辐照诱导的R743细胞的凋亡，而PSPC1过表达则降低了CNE2细胞的凋亡。放射后，PSPC1 KO细胞的迁移和侵袭能力明显降低。生物信息学分析发现SFPQ是PSPC1相互作用蛋白，PSPC1 KO导致SFPQ下调。此外，PSPC1 KO增强了裸鼠异种移植肿瘤的放射敏感性。结论：PSPC1是提高鼻咽癌放疗后细胞存活和扩散的关键因素。靶向PSPC1或其下游通路可能为克服鼻咽癌细胞的辐射耐药和转移提供新的策略。

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PSPC1 knockout promotes radiosensitivity, inhibits EMT, and metastasis of nasopharyngeal carcinoma cells

Purpose

Paraspeckle component 1 (PSPC1) is upregulated in numerous cancers and is associated with reduced patient survival rates. Our previous research indicated that elevated PSPC1 levels in nasopharyngeal carcinoma (NPC) are positively linked to radiation resistance and tumor metastasis, two primary clinical challenges in NPC treatment. However, the precise role of PSPC1 in radiation resistance and metastasis of NPC cells remains unclear. This study aimed to explore the molecular mechanisms by which PSPC1 influences radiation resistance and metastasis in NPC.

Methods

Using the radiation-resistant R743 and radiosensitive CNE2 cell lines of NPC, we examined the impact of PSPC1 expression on post-radiation survival, cell cycle progression, apoptosis, migration, invasion, and tumor growth. CRISPR/Cas9 genome editing was employed to generate PSPC1 knockout (KO) lines in R743 cells, while PSPC1 overexpression (pcD-PSPC1) was achieved in CNE2 cells via pcDNA3.1(+)-PSPC1 plasmid transfection.

Results

PSPC1 knockout converted R743 cells from radioresistant to radiosensitive, whereas PSPC1 overexpression decreased radiosensitivity in CNE2 cells. Cell cycle analysis revealed that PSPC1 KO arrested R743 cells in the G2/M phase post-irradiation, while PSPC1 overexpression prevented G2/M phase arrest in CNE2 cells. PSPC1 KO increased irradiation-induced apoptosis in R743 cells, whereas PSPC1 overexpression decreased it in CNE2 cells. Post-radiation, PSPC1 KO cells showed significantly reduced migration and invasion abilities. Bioinformatics analysis identified SFPQ as a PSPC1-interacting protein, with PSPC1 KO resulting in SFPQ downregulation. Additionally, PSPC1 KO enhanced the radiosensitivity of xenografted tumors in nude mice.

Conclusion

Our findings suggest that PSPC1 is a pivotal factor in enhancing the survival and spread of NPC cells post-radiation. Targeting PSPC1 or its downstream pathways could offer novel strategies to overcome radiation resistance and metastasis in NPC cells.

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.