由于胰腺癌是一种致命疾病，其机制尚不清楚。尿道上皮癌抗原1(UCA1)是一种长链非编码RNA (lncRNA)，最早在膀胱癌中报道，具有致癌基因的作用。然而，UCA1在胰腺癌中的调控作用和机制仍然未知。本研究旨在调查UCA1在胰腺癌组织中的表达水平和预后价值，以及UCA1在调控细胞增殖、凋亡和转移中的作用和机制。我们使用原位杂交(ISH)法检测了组织中的UCA1表达水平，并通过单变量和多变量生存分析评估了其预后价值。在体外实验中，通过细胞计数试剂盒分析、Edu实验和克隆形成实验评估了细胞增殖；通过流式细胞术评估了凋亡；通过划痕愈合和Transwell实验检测了细胞迁移和侵袭能力；通过Western blot检测了与凋亡相关的分子和上皮间质转化(EMT)标志物。在动物实验中，建立了裸鼠胰腺癌皮下移植模型以观察肿瘤生长。通过蛋白质组学、生物信息学分析、荧光素酶报告基因实验和救治实验探索了UCA1的调控机制。ISH染色显示，癌组织(n=94)和肿瘤邻近组织(n=73)之间的UCA1水平差异不显著。生存分析表明，高表达的UCA1是胰腺癌的不利预后因子。通过使用siRNA下调UCA1，明显抑制了细胞增殖，降低了细胞迁移和侵袭能力，诱导了细胞凋亡，抑制了EMT。此外，我们证明了UCA1通过抑制miR-582-5p而正调节BRCC3的表达。救治实验表明，无论是抑制miR-582-5p的表达还是增强BRCC3的表达，都可以在一定程度上减弱UCA1下调对抗肿瘤的作用。UCA1在胰腺癌中具有致癌基因的作用，部分通过调节miR-582-5p/BRCC3来实现，这可能成为胰腺癌的新治疗靶点。版权所有 © 2023 Hu, Wu and Xu.

As a fatal disease, the mechanism of pancreatic cancer is unclear. Urothelial carcinoma antigen 1(UCA1), a long noncoding RNA (lncRNA) that was first reported in bladder cancer, acts as an oncogene. However, the regulatory role and mechanism of UCA1 in pancreatic cancer remain unknown. This study aims to investigate the expression level and prognostic value of UCA1 in pancreatic cancer tissues, the effects and mechanism of UCA1 in regulating cell proliferation, apoptosis and metastasis.UCA1 expression levels in tissues were detected by in situ hybridization (ISH) and the prognostic value was evaluated by univariate and multivariate survival analysis. For in vitro experiments, proliferation was evaluated by a cell count kit assay, Edu experiments, and a clone formation assay. Apoptosis was evaluated by fluorescence-activated cell sorting flow-cytometry. Cell migration and invasion capacities were detected by wound healing and transwell assays. Western blots were performed to detect apoptotic associated molecules and epithelial-mesenchymal transition (EMT) markers. For the in vivo experiment, subcutaneous transplantation models of pancreatic cancer in nude mice were established to observe the tumor growth. The regulatory mechanism of UCA1 was explored by proteomics, bioinformatic analysis, luciferase reporter assays, and rescue experiments.ISH staining revealed that UCA1 levels between cancer tissues (n=94) and tumor-adjacent tissues (n=73) did not show significant differences. Survival analysis indicated that high expression of UCA1 was an unfavorable prognosis factor for pancreatic cancer. Downregulation of UCA1 by siRNA significantly inhibited cell proliferation, decreased the capacities of cell migration and invasion, induced cell apoptosis, and inhibited EMT. Furthermore, we demonstrated that UCA1 positively regulated the expression of BRCC3 by inhibiting miR-582-5p. Rescue experiments indicated that either inhibiting the expression of miR-582-5p or enhancing expression of BRCC3 could partly attenuate the antitumor effects of downregulation of UCA1.UCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which could be a new therapeutic target for pancreatic cancer.Copyright © 2023 Hu, Wu and Xu.