Dataset Information

Extracellular vesicles from human umbilical cord mesenchymal stem cells treated with siRNA against ELFN1-AS1 suppress colon adenocarcinoma proliferation and migration.

ABSTRACT: 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 in vitro. 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.

SUBMITTER: Dong L

PROVIDER: S-EPMC6895508 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Extracellular vesicles from human umbilical cord mesenchymal stem cells treated with siRNA against ELFN1-AS1 suppress colon adenocarcinoma proliferation and migration.

Dong Liyang L Ding Chao C Zheng Tingting T Pu Yanan Y Liu Jiameng J Zhang Wenzhe W Xue Fei F Kang Ping P Ma Yongbin Y Wang Xuefeng X Mao Chaoming C

American journal of translational research 20191115 11

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 w ...[more]

PMID: 31814902

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Project description:BackgroundSpinal cord injury (SCI) is an inflammatory condition, and excessive adenosine triphosphate (ATP) is released into the extracellular space, which can be catabolized into adenosine by CD73. Extracellular vesicles have been designed as nano drug carriers in many diseases. However, their impacts on delivery of CD73 after SCI are not yet known. We aimed to construct CD73 modified extracellular vesicles and explore the anti-inflammatory effects after SCI.MethodsCD73 engineered extracellular vesicles (CD73+ hucMSC-EVs) were firstly established, which were derived from human umbilical cord mesenchymal stem cells (hucMSCs) transduced by lentiviral vectors to upregulate the expression of CD73. Effects of CD73+ hucMSC-EVs on hydrolyzing ATP into adenosine were detected. The polarization of M2/M1 was verified by immunofluorescence. Furthermore, A2aR and A2bR inhibitors and A2bR knockdown cells were used to investigate the activated adenosine receptor. Biomarkers of microglia and levels of cAMP/PKA were also detected. Repetitively in vivo study, morphology staining, flow cytometry, cytokine analysis, and ELISA assay, were also applied for verifications.ResultsCD73+ hucMSC-EVs reduced concentration of ATP and promoted the level of adenosine. In vitro experiments, CD73+ hucMSC-EVs increased macrophages/microglia M2:M1 polarization, activated adenosine 2b receptor (A2bR), and then promoted cAMP/PKA signaling pathway. In mice using model of thoracic spinal cord contusion injury, CD73+ hucMSC-EVs improved the functional recovery after SCI through decreasing the content of ATP in cerebrospinal fluid and improving the polarization from M1 to M2 phenotype. Thus, the cascaded pro-inflammatory cytokines were downregulated, such as TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokines were upregulated, such as IL-10 and IL-4.ConclusionsCD73+ hucMSC-EVs ameliorated inflammation after spinal cord injury by reducing extracellular ATP, promoting A2bR/cAMP/PKA pathway and M2/M1 polarization. CD73+ hucMSC-EVs might be promising nano drugs for clinical application in SCI therapy.

Dataset Information

Extracellular vesicles from human umbilical cord mesenchymal stem cells treated with siRNA against ELFN1-AS1 suppress colon adenocarcinoma proliferation and migration.

Publications

Extracellular vesicles from human umbilical cord mesenchymal stem cells treated with siRNA against ELFN1-AS1 suppress colon adenocarcinoma proliferation and migration.

Similar Datasets

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