BackgroundPancreatic cancer (PC) is a type of malignant gastrointestinal tumor. Long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) has been reported to stimulate proliferation, migration and invasion in several types of tumors. However, the role of MCM3AP-AS1 in PC remains unclear.MethodsMCM3AP-AS1, microRNA miR-138-5p (miR-138-5p) and FOXK1 levels were detected using quantitative real time PCR. Cell proliferation, migration and invasion were analyzed. Dual luciferase reporter assay was used to confirm the relationship between MCM3AP-AS1 and miR-138-5p, between miR-138-5p and FOXK1. Protein levels were identified using western blot analysis.ResultsMCM3AP-AS1 overexpression promoted proliferation, migration and invasion in PC cells. MCM3AP-AS1 silencing showed a suppressive effect on cell growth in PC cells. Moreover, MCM3AP-AS1 knockdown suppressed tumor growth in mice. Dual luciferase reporter assay demonstrated MCM3AP-AS1 could sponge microRNA-138-5p (miR-138-5p), and FOXK1 could bind with miR-138-5p. Positive correlation between MCM3AP-AS1 and FOXK1 was testified, as well as negative correlation between miR-138-5p and FOXK1. MCM3AP-AS1 promoted FOXK1 expression by targeting miR-138-5p, and MCM3AP-AS1 facilitated growth and invasion in PC cells by FOXK1.ConclusionMCM3AP-AS1 promoted growth and migration through modulating miR-138-5p/FOXK1 axis in PC, providing insights into MCM3AP-AS1/miR-138-5p/FOXK1 axis as novel candidates for PC therapy from bench to clinic.

中文翻译：

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长链非编码RNA MCM3AP-AS1通过海绵miR-138-5p调节FOXK1促进胰腺癌生长和迁移

背景胰腺癌（PC）是一种消化道恶性肿瘤。据报道，长链非编码 RNA MCM3AP 反义 RNA 1 (MCM3AP-AS1) 可刺激多种肿瘤的增殖、迁移和侵袭。然而，MCM3AP-AS1在PC中的作用仍不清楚。方法使用定量实时PCR检测MCM3AP-AS1、microRNA miR-138-5p（miR-138-5p）和FOXK1水平。分析细胞增殖、迁移和侵袭。双荧光素酶报告基因检测用于确认 MCM3AP-AS1 和 miR-138-5p 之间、miR-138-5p 和 FOXK1 之间的关系。使用蛋白质印迹分析鉴定蛋白质水平。结果MCM3AP-AS1过表达促进PC细胞的增殖、迁移和侵袭。MCM3AP-AS1 沉默显示出对 PC 细胞生长的抑制作用。而且，MCM3AP-AS1 敲低抑制了小鼠的肿瘤生长。双荧光素酶报告基因检测表明 MCM3AP-AS1 可以吸收 microRNA-138-5p (miR-138-5p)，FOXK1 可以与 miR-138-5p 结合。证实了 MCM3AP-AS1 和 FOXK1 之间的正相关，以及 miR-138-5p 和 FOXK1 之间的负相关。MCM3AP-AS1通过靶向miR-138-5p促进FOXK1表达，MC​​M3AP-AS1通过FOXK1促进PC细胞的生长和侵袭。结论MCM3AP-AS1通过调节PC中的miR-138-5p/FOXK1轴促进生长和迁移，提供见解进入 MCM3AP-AS1/miR-138-5p/FOXK1 轴，作为从工作台到临床的 PC 治疗的新候选者。证实了 MCM3AP-AS1 和 FOXK1 之间的正相关，以及 miR-138-5p 和 FOXK1 之间的负相关。MCM3AP-AS1通过靶向miR-138-5p促进FOXK1表达，MC​​M3AP-AS1通过FOXK1促进PC细胞的生长和侵袭。结论MCM3AP-AS1通过调节PC中的miR-138-5p/FOXK1轴促进生长和迁移，提供见解进入 MCM3AP-AS1/miR-138-5p/FOXK1 轴，作为从工作台到临床的 PC 治疗的新候选者。证实了 MCM3AP-AS1 和 FOXK1 之间的正相关，以及 miR-138-5p 和 FOXK1 之间的负相关。MCM3AP-AS1通过靶向miR-138-5p促进FOXK1表达，MC​​M3AP-AS1通过FOXK1促进PC细胞的生长和侵袭。结论MCM3AP-AS1通过调节PC中的miR-138-5p/FOXK1轴促进生长和迁移，提供见解进入 MCM3AP-AS1/miR-138-5p/FOXK1 轴，作为从工作台到临床的 PC 治疗的新候选者。