Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive pancreatic cancer with poor survival rate. Circular RNAs (circRNAs) signatures have been identified in some human cancers, but there are little data concerning their presence in PDAC. We investigated the role of hsa_circ_001653, a newly identified circRNA, in the development of PDAC. hsa-circ-001653 expression was measured in 83 paired normal and tumor tissues surgically resected from PDAC patients. Phenotypic changes of PDAC cells were evaluated by assays for cell viability, cell cycle, invasion, and apoptosis. Tube-like structure formation of human umbilical vein endothelial cells (HUVECs) was examined in the presence of PDAC cells. Cross-talk between hsa_circ_001653 and microRNA-377 (miR-377)/human homeobox C6 (HOXC6) was assessed using dual-luciferase reporter assay, Ago2 immunoprecipitation, and northern blot analysis. Nude mice were inoculated with human PDAC cells for in vivo analysis. hsa_circ_001653 was an upregulated circRNA in PDAC. Silencing of hsa_circ_001653 in PDAC cells via RNA interference inhibited cell viability, cell-cycle progression, in vitro angiogenesis, and invasive properties, showing a pro-apoptotic effect. hsa_circ_001653 was found to bind to miR-377, which in turn repressed HOXC6 expression. Inhibition of miR-377 by its specific inhibitor restored cell viability, cell-cycle progression, in vitro angiogenesis, and invasive properties in PDAC cells lacking endogenous hsa_circ_001653. When nude mice were inoculated with human PDAC cells, inhibition of hsa_circ_001653 had a therapeutic effect. Collectively, the present study provides an enhanced understanding of hsa_circ_001653 as a therapeutic target for PDAC.

胰腺导管腺癌 (PDAC) 是一种极具侵袭性的胰腺癌，生存率很低。已经在一些人类癌症中鉴定出环状 RNA (circRNA) 特征，但关于它们在 PDAC 中存在的数据很少。我们调查了新发现的 circRNA hsa_circ_001653 在 PDAC 发展中的作用。在从 PDAC 患者手术切除的 83 对正常和肿瘤组织中测量了 hsa-circ-001653 表达。通过细胞活力、细胞周期、侵袭和细胞凋亡测定评估 PDAC 细胞的表型变化。在 PDAC 细胞存在的情况下检查人脐静脉内皮细胞 (HUVEC) 的管状结构形成。hsa_circ_001653 和 microRNA-377 (miR-377)/人类同源框 C6 (HOXC6) 之间的串扰使用双荧光素酶报告基因分析进行评估，Ago2 免疫沉淀和 northern 印迹分析。裸鼠接种人PDAC细胞用于体内分析。hsa_circ_001653 是 PDAC 中上调的 circRNA。通过 RNA 干扰在 PDAC 细胞中沉默 hsa_circ_001653 可抑制细胞活力、细胞周期进程、体外血管生成和侵袭特性，显示出促凋亡作用。hsa_circ_001653 被发现与 miR-377 结合，miR-377 反过来抑制 HOXC6 表达。其特异性抑制剂对 miR-377 的抑制可恢复缺乏内源性 hsa_circ_001653 的 PDAC 细胞的细胞活力、细胞周期进程、体外血管生成和侵袭特性。当裸鼠接种人PDAC细胞后，抑制hsa_circ_001653具有治疗作用。总的来说，本研究加深了对 hsa_circ_001653 作为 PDAC 治疗靶点的理解。