Chen Tengxiang, Lei Shan, Zeng Zhirui, Zhang Jinjuan, Xue Yan, Sun Yuanmei, Lan Jinzhi, Xu Su, Mao Dahua, Guo Bing
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou 550009, P.R. China.
Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550009, P.R. China.
Oncol Rep. 2020 Mar;43(3):930-942. doi: 10.3892/or.2020.7480. Epub 2020 Jan 27.
The biological function of long non‑coding RNA00261 (Linc00261) has been widely investigated in various types of cancer. The aim of the present study was to explore the role of Linc00261 in pancreatic cancer (PC). The expression of Linc00261 in patients with PC and PC cell lines was assessed using reverse transcription‑quantitative PCR and the association of Linc00261 expression with survival was analyzed in the online database, GEPIA. The effects of Linc00261 on PC cell metastasis in vitro and in vivo were determined using a wound healing assay, Transwell invasion assays and a nude mouse model of liver metastasis. The relationship between Linc00261, the miR‑552‑5p/forkhead box O3 (FOXO3) axis and the Wnt signaling pathway were determined using bioinformatics analysis, dual luciferase assay and western blotting. Linc00261 expression was significantly decreased in PC tissues and cell lines, and reduced expression was associated with less favorable outcomes in patients with PC. Linc00261 overexpression inhibited migration and invasion of PC cells in vitro, whereas knockdown of Linc00261 increased migration and invasion. Linc00261 overexpression also decreased metastasis of PC cells in vivo. Linc00261 was revealed to directly bind to microRNA (miR)‑552‑5p and to decrease the expression of miR‑552‑5p. In addition, Linc00261 overexpression increased the expression of FOXO3, a target gene of miR‑552‑5p, as well as inhibited the Wnt signaling pathway. Overexpression of miR‑552‑5p in Linc00261‑overexpressing PC cells increased migration and invasion, as well as decreased the expression of FOXO3 and members of the Wnt signaling pathway. Collectively, the present study demonstrated that Linc00261 inhibited metastasis and the Wnt signaling pathway of PC by regulating the miR‑552‑5p/FOXO3 axis. Linc00261 may suppress the development of PC, and serve as a potential biomarker and effective target for the diagnosis and treatment of PC.
长链非编码RNA00261（Linc00261）的生物学功能已在多种癌症类型中得到广泛研究。本研究的目的是探讨Linc00261在胰腺癌（PC）中的作用。采用逆转录定量PCR评估Linc00261在PC患者和PC细胞系中的表达，并在在线数据库GEPIA中分析Linc00261表达与生存率的相关性。使用伤口愈合试验、Transwell侵袭试验和肝转移裸鼠模型确定Linc00261对PC细胞体外和体内转移的影响。使用生物信息学分析、双荧光素酶测定和蛋白质印迹法确定Linc00261、miR-552-5p/叉头框O3（FOXO3）轴与Wnt信号通路之间的关系。Linc00261在PC组织和细胞系中的表达显著降低，表达降低与PC患者较差的预后相关。Linc00261过表达抑制PC细胞体外迁移和侵袭，而敲低Linc00261则增加迁移和侵袭。Linc00261过表达还可降低PC细胞体内转移。研究发现Linc00261直接与微小RNA（miR）-552-5p结合并降低miR-552-5p的表达。此外，Linc0026过表达增加了miR-552-5p的靶基因FOXO3的表达，并抑制了Wnt信号通路。在Linc00261过表达的PC细胞中过表达miR-552-5p可增加迁移和侵袭，并降低FOXO3和Wnt信号通路成员的表达。总的来说，本研究表明Linc00261通过调节miR-552-5p/FOXO3轴抑制PC的转移和Wnt信号通路。Linc00261可能抑制PC的发展，并作为PC诊断和治疗的潜在生物标志物和有效靶点。
