Long noncoding RNA DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be highly associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. This study aimed to explore the role of DGCR5 in PC. It was revealed that DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate DNA topoisomerase 2-alpha (TOP2A) and inhibit Wnt/β-catenin pathway. In addition, it was found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that PAX5 (Paired Box 5) could bind to the promoter region of DGCR5 and increase its transcription. The results of the present study indicated that DGCR5 may be a potential diagnostic biomarker and therapeutic target for PC.

中文翻译：

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DGCR5被PAX5激活，通过靶向miR-3163/TOP2A和激活Wnt/β-catenin通路促进胰腺癌发生

长链非编码 RNA DiGeorge 综合征关键区基因 5 (DGCR5) 已被证明与癌症发展高度相关。然而，DGCR5 在胰腺癌 (PC) 中的生物学作用和分子机制仍然很大程度上未知。本研究旨在探讨 DGCR5 在 PC 中的作用。结果表明，与邻近的正常组织相比，DGCR5 在 PC 组织中高表达，并且与 PC 患者的不良预后相关。此外，DGCR5 耗竭通过增加细胞凋亡和诱导体外 G0/G1 细胞周期停滞来抑制增殖、迁移和侵袭。此外，异种移植试验证实 DGCR5 在体内促进 PC 肿瘤生长。从机制上讲，发现 DGCR5 通过海绵 miR-3163 充当 ceRNA 来调节 DNA 拓扑异构酶 2-α (TOP2A) 并抑制 Wnt/β-连环蛋白途径。此外，发现DGCR5下调可以增强PC细胞对吉西他滨的敏感性，ChIP检测显示PAX5（Paired Box 5）可以与DGCR5的启动子区域结合并增加其转录。本研究结果表明，DGCR5可能是PC的潜在诊断生物标志物和治疗靶点。