Pseudogene pituitary tumor-transforming 3 (PTTG3P) is emerging as a key player in the development and progression of cancer. However, the biological role and clinical significance of PTTG3P in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we found that PTTG3P was significantly upregulated in PDAC tissues. Elevated PTTG3P expression correlated with larger tumor size and worse differentiation, and reduced overall survival. Bioinformatics and experimental evidence revealed that PTTG3P promoted malignant phenotypes and FoxM1 signaling pathway in PDAC cells. Mechanistically, PTTG3P functions as a microRNA sponge to positively regulate the expression of FoxM1 through sponging miR-132/212-3p. Moreover, it showed that FoxM1 transcriptionally activated PTTG3P expression, thus forming a feedback loop to promote the aggressiveness of PDAC cells. Taken together, our findings suggest that PTTG3P promotes PDAC progression through PTTG3P/miR-132/212-3p/FoxM1 feedforward circuitry and it may serve as a promising diagnostic marker or target for treatment in PDAC patients.

伪基因垂体瘤转化3（PTTG3P）成为癌症发展和进程中的关键角色。然而，PTTG3P在胰腺导管腺癌（PDAC）中的生物学作用和临床意义仍不清楚。在这里，我们发现PTTG3P在PDAC组织中显着上调。PTTG3P表达升高与更大的肿瘤大小和更差的分化相关，并降低了总生存期。生物信息学和实验证据表明，PTTG3P促进了PDAC细胞的恶性表型和FoxM1信号通路。从机制上讲，PTTG3P充当microRNA海绵，通过海绵化miR-132 / 212-3p来积极调节FoxM1的表达。而且，它表明FoxM1转录激活了PTTG3P表达，从而形成一个反馈环路，以促进PDAC细胞的侵略性。综上所述，我们的研究结果表明PTTG3P通过PTTG3P / miR-132 / 212-3p / FoxM1前馈电路促进PDAC的进展，它可能成为PDAC患者的有希望的诊断标记或治疗靶标。