Dong Liyang, Ding Chao, Zheng Tingting, Pu Yanan, Liu Jiameng, Zhang Wenzhe, Xue Fei, Kang Ping, Ma Yongbin, Wang Xuefeng, Mao Chaoming
Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University Zhenjiang 212000, Jiangsu, China.
State Key Lab of Reproductive Medicine, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, Nanjing Medical University Nanjing 211166, Jiangsu, China.
Am J Transl Res. 2019 Nov 15;11(11):6989-6999. eCollection 2019.
Recent evidence has shown that long noncoding RNAs (lncRNAs) play major roles in tumorigenesis and cancer progression. The cancer genome atlas program (TCGA) database was used to screen colon adenocarcinoma (COAD)-related differentially expressed lncRNAs, which revealed that lncRNA ELFN1-AS1 was highly expressed in COAD. This study aimed to explore the regulatory role of ELFN1-AS1 in COAD and construct a gene delivery system based on extracellular vesicles (EVs). We found that ELFN1-AS1 levels were obviously increased in COAD patients and COAD tumor cells. Knockdown of ELFN1-AS1 expression by siRNA inhibited COAD cell proliferation and migration. Moreover, silencing ELFN1-AS1 significantly reduced the activation of extracellular signal-regulated protein kinase (Erk), up-regulated the protein expression of E-cadherin and down-regulated vimentin. In addition, we treated human umbilical cord mesenchymal stem cells (hUCMSCs) with siRNA-ELFN1-AS1 and found that EVs from siRNA-ELFN1-AS1-treated hUCMSCs could inhibit COAD cell proliferation and migration . These findings suggested that ELFN1-AS1 could promote the progression of COAD and that hUCMSC-EVs might be an attractive vehicle for the clinical administration of lncRNA-specific siRNAs in patients with COAD.
最近的证据表明,长链非编码RNA(lncRNAs)在肿瘤发生和癌症进展中起主要作用。利用癌症基因组图谱计划(TCGA)数据库筛选与结肠腺癌(COAD)相关的差异表达lncRNAs,结果显示lncRNA ELFN1-AS1在COAD中高表达。本研究旨在探讨ELFN1-AS1在COAD中的调控作用,并构建基于细胞外囊泡(EVs)的基因递送系统。我们发现,COAD患者和COAD肿瘤细胞中ELFN1-AS1水平明显升高。通过小干扰RNA(siRNA)敲低ELFN1-AS1表达可抑制COAD细胞增殖和迁移。此外,沉默ELFN1-AS1可显著降低细胞外信号调节蛋白激酶(Erk)的激活,上调E-钙黏蛋白的蛋白表达并下调波形蛋白。另外,我们用siRNA-ELFN1-AS1处理人脐带间充质干细胞(hUCMSCs),发现来自经siRNA-ELFN1-AS1处理的hUCMSCs的EVs可抑制COAD细胞增殖和迁移。这些发现表明,ELFN1-AS1可促进COAD的进展,并且hUCMSC-EVs可能是COAD患者临床应用lncRNA特异性siRNAs的有吸引力的载体。