Department of Stomatology, the Affiliated People's Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.
Department of Stomatology, the Affiliated People's Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.
Arch Oral Biol. 2024 Nov;167:106068. doi: 10.1016/j.archoralbio.2024.106068. Epub 2024 Aug 13.
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.
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.
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.
PRELP suppressed OSCC progression via inactivation of the NF-κB pathway. Targeting PRELP may be a potential approach for OSCC treatment.
本研究旨在探讨富含脯氨酸/精氨酸的 LE 重复蛋白（PRELP）作为细胞外基质中一种分泌蛋白在口腔鳞状细胞癌（OSCC）进展中的作用和分子机制。
通过基因集富集（GSE）138206、GSE37991 和 GSE23558 数据集以及细胞系分析了 OSCC 中 PRELP 的表达。还通过生物信息学分析证实了 PRELP 在头颈部鳞状细胞癌（HNSCC）中的表达及其与预后和免疫浸润的关系。通过 CCK-8、EdU、流式细胞术、Transwell、实时 PCR、免疫荧光和 Western blot 检测改变 OSCC 细胞中 PRELP 表达后对细胞增殖、凋亡、侵袭、上皮间质转化（EMT）和 NF-κB 激活的影响。此外，还使用 NF-κB 抑制剂 PDTC 来确认 PRELP 的调节机制。
PRELP 在 OSCC 组织、细胞和 HNSCC 样本中的表达较低。HNSCC 患者中 PRELP 表达较高与总生存期较长相关。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，而 PRELP 的下调促进 OSCC 细胞的增殖、侵袭和 EMT。此外，PRELP 的过表达促进细胞凋亡。机制上，PRELP 抑制了 p65 的磷酸化和核转位。PDTC 处理部分逆转了 PRELP 敲低对 OSCC 细胞恶性行为的影响。
PRELP 通过抑制 NF-κB 通路抑制 OSCC 的进展。靶向 PRELP 可能是治疗 OSCC 的一种潜在方法。
