Department of pathology, Affiliated hospital of Guilin Medical University, Guilin, 541001, Guangxi, China.
Scientific Research Center, Guilin Medical University, Guilin, 541001, Guangxi, China.
Int J Biol Sci. 2021 Jun 1;17(9):2223-2239. doi: 10.7150/ijbs.58026. eCollection 2021.
Overexpression of pyrroline-5-carboxylate reductase 1 (PYCR1) has been associated with the development of certain cancers; however, no studies have specifically examined the role of PYCR1 in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas expression array and meta-analysis conducted using the Gene Expression Omnibus database, we determined that was upregulated in HCC compared to adjacent nontumor tissues (P < 0.05). These data were verified using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry analysis. Additionally, patients with low PYCR1 expression showed a higher overall survival rate than patients with high expression. Furthermore, PYCR1 overexpression was associated with the female sex, higher levels of alpha-fetoprotein, advanced clinical stages (III and IV), and a younger age (< 45 years old). Silencing of inhibited cell proliferation, invasive migration, epithelial-mesenchymal transition, and metastatic properties in HCC and Using RNA sequencing and bioinformatics tools for data-dependent network analysis, we found binary relationships among PYCR1 and its interacting proteins in defined pathway modules. These findings indicated that PYCR1 played a multifunctional role in coordinating a variety of biological pathways involved in cell communication, cell proliferation and growth, cell migration, a mitogen-activated protein kinase cascade, ion binding, . The structural characteristics of key pathway components and PYCR1-interacting proteins were evaluated by molecular docking, and hotspot analysis showed that better affinities between PYCR1 and its interacting molecules were associated with the presence of arginine in the binding site. Finally, a candidate regulatory microRNA, miR-2355-5p, for mRNA was discovered in HCC. Overall, our study suggests that PYCR1 plays a vital role in HCC pathogenesis and may potentially serve as a molecular target for HCC treatment.
吡咯啉-5-羧酸还原酶 1 (PYCR1) 的过表达与某些癌症的发展有关；然而，尚无研究专门探讨 PYCR1 在肝细胞癌 (HCC) 中的作用。基于癌症基因组图谱表达谱和使用基因表达综合数据库进行的荟萃分析，我们确定与相邻非肿瘤组织相比，在 HCC 中上调（P < 0.05）。这些数据通过定量实时聚合酶链反应、western blot 和免疫组织化学分析得到验证。此外，PYCR1 低表达的患者总生存率高于高表达的患者。此外，PYCR1 过表达与女性、高水平的甲胎蛋白、较晚的临床分期 (III 和 IV) 和较年轻的年龄 (<45 岁) 相关。沉默抑制了 HCC 中的细胞增殖、侵袭性迁移、上皮-间充质转化和转移特性，并且使用 RNA 测序和数据依赖的网络分析的生物信息学工具，我们在定义的途径模块中发现了 PYCR1 与其相互作用蛋白之间的二元关系。这些发现表明，PYCR1 在协调涉及细胞通讯、细胞增殖和生长、细胞迁移、丝裂原激活蛋白激酶级联、离子结合、细胞代谢和细胞死亡等多种生物途径方面发挥了多功能作用。通过分子对接评估了关键途径成分和 PYCR1 相互作用蛋白的结构特征，热点分析表明，结合位点中存在精氨酸与 PYCR1 及其相互作用分子之间更好的亲和力相关。最后，在 HCC 中发现了候选调节 microRNA，miR-2355-5p，用于 mRNA。总体而言，我们的研究表明 PYCR1 在 HCC 发病机制中发挥着重要作用，并且可能成为 HCC 治疗的潜在分子靶标。
