Exosomal-lncRNA DLEUI Accelerates the Proliferation, Migration, and Invasion of Endometrial Carcinoma Cells by Regulating microRNA-E2F3
Exosomal-lncRNA DLEUI Accelerates the Proliferation, Migration, and Invasion of Endometrial Carcinoma Cells by Regulating microRNA-E2F3
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DOI：
10.2147/ott.s262661
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Xie, Xingmei
中科院分区：
文献类型：
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作者：
Jia, Jianjun;Guo, Suiqun;Xie, Xingmei
目的：长链非编码rna （lncRNAs）可能在包括子宫内膜癌（EC）在内的多种癌症中起致癌基因的作用。本研究旨在探讨淋巴细胞白血病（pleu1）中外泌体lncrna缺失对EC的调控机制。方法：采用定量逆转录聚合酶链式反应（qRT-PCR）检测EC组织或细胞中lncRNA DLEU1、microRNA-381-3p和E2F转录因子3 （E2F3）的表达水平。然后，我们分别通过MTT试验、伤口愈合试验和transwell侵袭试验分析了EC细胞的增殖、迁移和侵袭。采用Western blot法检测外泌体的鉴定。用共聚焦显微镜检测外泌体的摄取。通过构建细胞共培养体系，研究外泌体对EC细胞的影响。DLEU1、miR-381-3p和E2F3之间的相互作用通过双荧光素酶报告基因（DLR）检测得到证实。结果：LncRNA在EC组织和细胞中表达水平明显上调。敲低DLEU1可抑制EC细胞的增殖、迁移和侵袭。外泌体可以被周围的EC细胞吸收。MiR-381-3p是DLEU1的靶标，并被DLEU1负向调节。过表达miR-381-3p可抑制EC细胞的增殖、迁移和侵袭。此外，E2F3是miR-381-3p的靶基因，被miR-381-3p负向调节。miR-381-3p的上调和E2F3的下调逆转了外泌体pleu1对EC细胞的促进作用。结论：外泌体dlu1通过调节miR-381-3p/E2F3轴加速EC的发展，因此dlu1可能是治疗EC的可能的治疗靶点。
Purpose: 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 leukemial (DLEU1) on EC.Methods: The expression levels of lncRNA DLEU1, microRNA-381-3p and E2F Transcription Factor 3 (E2F3) 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 E2F3 were confirmed using the dual-luciferase reporter (DLR) assay.Results: 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, E2F3 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 E2F3 reversed the promoting effect of exosomal DLEU1 on EC cells.Conclusion: Exosomal DLEU1 accelerates the development of EC by regulating the miR-381-3p/E2F3 axis, thus DLEU1 may act as a possible therapeutic target for treating EC.