Wu Liping, Liu Yongcun, Guo Cheng, Shao Yuan
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061 Shaanxi China.
Department of Oncology, The First People's Hospital of Xianyang, Xianyang, 712000 Shaanxi China.
Cancer Cell Int. 2020 Jul 9;20:296. doi: 10.1186/s12935-020-01366-w. eCollection 2020.
Pancreatic ductal adenocarcinoma (PDAC), a subtype of pancreatic cancer, is a malignant tumor with unfavorable prognosis. Despite accumulating researches have made efforts on finding novel therapeutic methods for this disease, the underlying mechanism of long non-coding RNAs (lncRNAs) remains elusive. OIP5 antisense RNA 1 (OIP5-AS1) has been reported to play important role in the occurrence and development of multiple human cancers. This study was aimed at unveiling the regulatory role of OIP5-AS1 in PDAC.
RT-qPCR analysis revealed the OIP5-AS1 expression in PDAC tissues and adjacent normal ones. Kaplan-Meier method was applied to analyze the overall survival of patients with high or low level of OIP5-AS1. Gain- or loss-of function assays were performed to assess the effects of OIP5-AS1 knockdown on cell functions, including proliferation, migration and EMT process. Mechanism experiments, such as luciferase reporter and RNA pull-down assays proved the interaction between OIP5-AS1 and miR-429 as well as that between miR-429 and FOXD1.
OIP5-AS1 was up-regulated in PDAC tissues and cell lines, and high level of OIP5-AS1 indicated poor prognosis in PDAC patients. OIP5-AS1 knockdown hindered cell proliferation, migration and epithelial-mesenchymal transition (EMT) process, while overexpression of OIP5-AS1 caused the opposite results. OIP5-AS1 activated ERK pathway through up-regulating forkhead box D1 (FOXD1) expression by sponging miR-429. Furthermore, OIP5-AS1 facilitated cell growth in vivo.
OIP5-AS1 exerted oncogenic function in PDAC cells through targeting miR-429/FOXD1/ERK pathway.
胰腺导管腺癌（PDAC）是胰腺癌的一种亚型，是一种预后不良的恶性肿瘤。尽管越来越多的研究致力于寻找针对该疾病的新型治疗方法，但长链非编码RNA（lncRNAs）的潜在机制仍不清楚。据报道，OIP5反义RNA 1（OIP5-AS1）在多种人类癌症的发生和发展中起重要作用。本研究旨在揭示OIP5-AS1在PDAC中的调控作用。
RT-qPCR分析揭示了PDAC组织和相邻正常组织中OIP5-AS1的表达。采用Kaplan-Meier法分析OIP5-AS1水平高低的患者的总生存期。进行功能获得或缺失实验，以评估OIP5-AS1敲低对细胞功能的影响，包括增殖、迁移和上皮-间质转化（EMT）过程。荧光素酶报告基因和RNA下拉实验等机制实验证明了OIP5-AS1与miR-429之间以及miR-429与FOXD1之间的相互作用。
OIP5-AS1在PDAC组织和细胞系中上调，高水平的OIP5-AS1表明PDAC患者预后不良。OIP5-AS1敲低阻碍细胞增殖、迁移和上皮-间质转化（EMT）过程，而OIP5-AS1过表达则产生相反的结果。OIP5-AS1通过海绵化miR-429上调叉头框D1（FOXD1）表达来激活ERK通路。此外，OIP5-AS1促进体内细胞生长。
OIP5-AS1通过靶向miR-429/FOXD1/ERK通路在PDAC细胞中发挥致癌功能。
