Jia Jianjun, Guo Suiqun, Zhang Dong, Tian Xiaohui, Xie Xingmei
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou City, Guangdong Province 510632, People's Republic of China.
Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou City, Guangdong Province, People's Republic of China.
Onco Targets Ther. 2020 Aug 25;13:8651-8663. doi: 10.2147/OTT.S262661. eCollection 2020.
Long non-coding RNAs (lncRNAs) may act as oncogenes in several cancers, including endometrial carcinoma (EC). The purpose of the current study is to investigate the regulatory mechanism of exosomal-lncRNA deleted in lymphocytic leukemia1 (DLEU1) on EC.
The expression levels of lncRNA DLEU1, microRNA-381-3p and E2F Transcription Factor 3 () in EC tissues or cells were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We then analysed the proliferation, migration, and invasion of EC cells by performing the MTT assay, wound healing assay, and transwell invasion assay, respectively. Identification of exosomes was detected using Western blot assay. The uptake of exosomes was detected by a confocal microscope. The effects of exosomes on EC cells were investigated by construction of cell co-culture system. The interactions among DLEU1, miR-381-3p and were confirmed using the dual-luciferase reporter (DLR) assay.
LncRNA DLEU1 expression was highly up-regulated in EC tissues and cells. Knockdown of DLEU1 inhibited the proliferation, migration, and invasion of EC cells. Exosomes could be uptaken by the ambient EC cells. MiR-381-3p was a target of DLEU1 and was negatively modulated by DLEU1. Overexpression of miR-381-3p suppressed the proliferation, migration, and invasion of EC cells. Additionally, was the target gene of miR-381-3p and was negatively modulated by miR-381-3p. Upregulation of miR-381-3p and down-regulation of reversed the promoting effect of exosomal DLEU1 on EC cells.
Exosomal DLEU1 accelerates the development of EC by regulating the miR-381-3p/ axis, thus DLEU1 may act as a possible therapeutic target for treating EC.
长链非编码RNA（lncRNAs）在包括子宫内膜癌（EC）在内的多种癌症中可能作为癌基因发挥作用。本研究旨在探讨淋巴细胞白血病1缺失的外泌体lncRNA（DLEU1）对子宫内膜癌的调控机制。
采用定量逆转录-聚合酶链反应（qRT-PCR）检测子宫内膜癌组织或细胞中lncRNA DLEU1、微小RNA-381-3p和E2F转录因子3（E2F3）的表达水平。然后，分别通过MTT法、伤口愈合试验和Transwell侵袭试验分析子宫内膜癌细胞的增殖、迁移和侵袭能力。采用蛋白质免疫印迹法检测外泌体。通过共聚焦显微镜检测外泌体的摄取情况。通过构建细胞共培养系统研究外泌体对子宫内膜癌细胞的影响。采用双荧光素酶报告基因（DLR）试验证实DLEU1、miR-381-3p和E2F3之间的相互作用。
lncRNA DLEU1在子宫内膜癌组织和细胞中高度上调。敲低DLEU1可抑制子宫内膜癌细胞的增殖、迁移和侵袭。外泌体可被周围的子宫内膜癌细胞摄取。miR-381-3p是DLEU1的靶标，受DLEU1负调控。miR-381-3p过表达可抑制子宫内膜癌细胞的增殖、迁移和侵袭。此外，E2F3是miR-381-3p的靶基因，受miR-381-3p负调控。miR-381-3p上调和E2F3下调可逆转外泌体DLEU1对子宫内膜癌细胞的促进作用。
外泌体DLEU1通过调节miR-381-3p/E2F3轴加速子宫内膜癌的发展，因此DLEU1可能作为治疗子宫内膜癌的潜在治疗靶点。
