Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, P.R. China.
Department of Obstetrics and Gynecology, Zhabei Central Hospital of Jing'an, Shanghai 200070, P.R. China.
Oncol Rep. 2022 Oct;48(4). doi: 10.3892/or.2022.8399. Epub 2022 Sep 9.
The protein disulfide isomerase (PDI) gene family plays important roles in the maintenance of several cellular functions. Previous studies have showed that protein disulfide isomerase family A member 4 (PDIA4) is aberrantly expressed in several types of cancer, and correlates with prognosis of patients. However, the role of PDIA4 in cervical cancer remains unclear. In the present study, the expression pattern of PDIA4 from both public database and immunohistochemical analysis in cervical samples was analyzed. Cell Counting Kit‑8 and Transwell assays were performed to determine the effect of PDIA4 on cervical cancer cell proliferation and migration. Gene set enrichment analysis (GSEA) was used to provide the associated enriched pathways of PDIA4 in regulating cervical tumorigenesis. It was observed that mRNA expression and protein level of PDIA4 were upregulated in cervical cancer tissues. High expression of PDIA4 was significantly associated with poor overall survival (P=0.0095) and relapse‑free survival (P=0.0019) in The Cancer Genome Atlas cohort. Knockdown of PDIA4 inhibited cervical cancer cell proliferation and migration. Moreover, PDIA4 affected the expression of proliferation‑related molecules (cyclin D1 and PCNA) and migration‑related molecules (E‑cadherin and Vimentin). Additionally, GSEA revealed that PDIA4 was significantly associated with gene signatures involving glycan biosynthesis, glycosaminoglycan degradation and protein export. In conclusion, the present findings highlighted the importance of PDIA4 in cervical oncogenesis, and suggested that targeting PDIA4 may be a potential therapeutic application for cervical cancer.
蛋白质二硫键异构酶（PDI）基因家族在维持多种细胞功能方面发挥着重要作用。先前的研究表明，蛋白质二硫键异构酶家族 A 成员 4（PDIA4）在几种类型的癌症中异常表达，并与患者的预后相关。然而，PDIA4 在宫颈癌中的作用尚不清楚。在本研究中，分析了公共数据库和宫颈样本免疫组织化学分析中 PDIA4 的表达模式。通过细胞计数试剂盒-8 和 Transwell 测定来确定 PDIA4 对宫颈癌细胞增殖和迁移的影响。基因集富集分析（GSEA）用于提供 PDIA4 调节宫颈肿瘤发生的相关富集途径。结果观察到，PDIA4 的 mRNA 表达和蛋白水平在宫颈癌组织中上调。在癌症基因组图谱队列中，PDIA4 高表达与总生存期（P=0.0095）和无复发生存期（P=0.0019）显著相关。PDIA4 敲低抑制了宫颈癌细胞的增殖和迁移。此外，PDIA4 影响了增殖相关分子（细胞周期蛋白 D1 和 PCNA）和迁移相关分子（E-钙黏蛋白和波形蛋白）的表达。此外，GSEA 表明 PDIA4 与涉及糖基生物合成、糖胺聚糖降解和蛋白质输出的基因特征显著相关。综上所述，本研究结果强调了 PDIA4 在宫颈癌发生中的重要性，并表明靶向 PDIA4 可能是宫颈癌的一种潜在治疗应用。
