Wang Guoying, Ni Xin, Wang Jintian, Dai Ming
Department of Gastroenterology, Liyang People's Hospital, Liyang City, Jiangsu, China.
Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
Pathol Res Pract. 2023 Aug;248:154645. doi: 10.1016/j.prp.2023.154645. Epub 2023 Jun 27.
Brain Type Glycogen Phosphorylase (PYGB) has been revealed to participate in the progression of multiple human cancers. Nevertheless, the clinical significance and biological function of PYGB in pancreatic ductal adenocarcinoma (PAAD) remains unclarified. This study first analyzed the expression pattern, diagnostic value, and prognostic significance of PYGB in PAAD using the TCGA database. Subsequently, western blot assessed the protein expression of genes in PAAD cells. The viability, apoptosis, migration, and invasion of PAAD cells were assessed by CCK-8, TUNEL, and Transwell assays. Finally, in vivo experiment evaluated the effect of PYGB on PAAD tumor growth and metastasis. Through our investigation, it was revealed that PYGB had extremely high expression in PAAD and predicted a worse prognosis in patients with PAAD. Besides, the aggressiveness of PAAD cells could be suppressed or enhanced by depleting or supplementing PYGB. In addition, we demonstrated that METTL3 enhanced the translation of PYGB mRNA in an mA-YTHDF1-dependent manner. Moreover, PYGB was revealed to regulate the malignant behaviors of PAAD cells by the mediation of the NF-κB signaling. Finally, PYGB depletion suppressed the growth and distant metastasis of PAAD in vivo. To conclude, our results indicated that METTL3-mediated mA modification of PYGB exerted the tumor-promotive effect on PAAD through NF-κB signaling, suggesting PYGB is a potential therapeutic target in PAAD.
脑型糖原磷酸化酶（PYGB）已被揭示参与多种人类癌症的进展。然而，PYGB在胰腺导管腺癌（PAAD）中的临床意义和生物学功能仍不明确。本研究首先利用TCGA数据库分析了PYGB在PAAD中的表达模式、诊断价值和预后意义。随后，蛋白质印迹法评估了PAAD细胞中基因的蛋白表达。通过CCK-8、TUNEL和Transwell实验评估PAAD细胞的活力、凋亡、迁移和侵袭能力。最后，体内实验评估了PYGB对PAAD肿瘤生长和转移的影响。通过我们的研究发现，PYGB在PAAD中表达极高，并预示着PAAD患者预后较差。此外，通过消耗或补充PYGB可以抑制或增强PAAD细胞的侵袭性。此外，我们证明METTL3以mA-YTHDF1依赖的方式增强了PYGB mRNA的翻译。而且，PYGB被揭示通过NF-κB信号传导介导来调节PAAD细胞的恶性行为。最后，敲低PYGB可抑制PAAD在体内的生长和远处转移。总之，我们的结果表明，METTL3介导的PYGB的mA修饰通过NF-κB信号传导对PAAD发挥促肿瘤作用，提示PYGB是PAAD潜在的治疗靶点。
