PRELP inhibits the progression of oral squamous cell carcinoma via inactivation of the NF-κB pathway

IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE
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引用次数: 0

Abstract

Objectives

The aim of this study was to investigate the role and molecular mechanism of proline/arginine-rich end leucine-rich repeat protein (PRELP), a secreted protein in extracellular matrix, in oral squamous cell carcinoma (OSCC) progression.

Design

PRELP expression in OSCC was analyzed in the Gene Set Enrichment (GSE) 138206, GSE37991, and GSE23558 datasets as well as cell lines. Also, PRELP expression and its relationship with prognosis and immune infiltration in head and neck squamous cell carcinoma (HNSCC) were confirmed by bioinformatics analysis. The proliferation, apoptosis, invasion, epithelial-to-mesenchymal transition (EMT) and NF-κB activation were detected after alteration of PRELP expression in OSCC cells using CCK-8, EdU, flow cytometry, Transwell, real-time PCR, immunofluorescence and Western blot. Additionally, an NF-κB inhibitor PDTC was used to confirm the regulation mechanism of PRELP.

Results

The expression of PRELP in OSCC tissues, cells and in HNSCC samples was low. HNSCC patients with higher PRELP expression was associated with longer overall survival. A positive correlation between PRELP expression and immune cell infiltration was found in HNSCC. Upregulation of PRELP inhibited, whereas PRELP silencing promoted, the proliferation, invasion and EMT of OSCC cells. Also, overexpression of PRELP promoted cell apoptosis. Mechanistically, PRELP suppressed p65 phosphorylation and nuclear translocation. And PDTC treatment partially reversed the influences of PRELP knockdown on the malignant behaviors in OSCC cells.

Conclusion

PRELP suppressed OSCC progression via inactivation of the NF-κB pathway. Targeting PRELP may be a potential approach for OSCC treatment.

PRELP 通过抑制 NF-κB 通路抑制口腔鳞状细胞癌的发展
设计通过基因组富集(GSE)138206、GSE37991和GSE23558数据集以及细胞系分析PRELP在OSCC中的表达。此外,还通过生物信息学分析证实了头颈部鳞状细胞癌(HNSCC)中 PRELP 的表达及其与预后和免疫浸润的关系。利用CCK-8、EdU、流式细胞术、Transwell、实时PCR、免疫荧光和Western blot检测了PRELP表达改变后OSCC细胞的增殖、凋亡、侵袭、上皮细胞向间质转化(EMT)和NF-κB活化。结果PRELP在OSCC组织、细胞和HNSCC样本中的表达量较低。PRELP表达较高的HNSCC患者总生存期较长。在 HNSCC 中发现 PRELP 表达与免疫细胞浸润呈正相关。PRELP 的上调抑制了 OSCC 细胞的增殖、侵袭和 EMT,而 PRELP 的沉默则促进了它们的增殖、侵袭和 EMT。此外,过表达 PRELP 还会促进细胞凋亡。从机理上讲,PRELP 可抑制 p65 磷酸化和核转位。结论 PRELP通过抑制NF-κB通路抑制OSCC的进展。以PRELP为靶点可能是治疗OSCC的一种潜在方法。
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来源期刊
Archives of oral biology
Archives of oral biology 医学-牙科与口腔外科
CiteScore
5.10
自引率
3.30%
发文量
177
审稿时长
26 days
期刊介绍: Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including: Cell and molecular biology Molecular genetics Immunology Pathogenesis Cellular microbiology Embryology Syndromology Forensic dentistry
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