miR-451a 被选择性地分类到外泌体中,并通过 CAB39 促进食管鳞状细胞癌的进展

IF 4.8 3区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Lu Wang, Huijuan Liu, Qinglu Wu, Yiqian Liu, Zhenpeng Yan, Guohui Chen, Yao Shang, Songrui Xu, Qichao Zhou, Ting Yan, Xiaolong Cheng
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引用次数: 0

摘要

外泌体是新出现的细胞-细胞通讯介质,它从细胞中分泌出来,并可能在细胞生物学过程中被输送到受体细胞中。在这里,我们研究了食管鳞状细胞癌(ESCC)细胞中的微RNA(miRNA)表达。我们在KYSE150和KYSE450细胞系的外泌体和细胞中进行了miRNA测序。在这些差异表达的 miRNA 中,有 20 个 miRNA 在细胞和外泌体中被检测到。热图显示,外泌体中的miR-451a水平高于ESCC细胞。此外,miRNA牵引试验和外泌体蛋白质组数据显示,miR-451a与YWHAE相互作用。过度表达YWHAE会导致miR-451a在外泌体而不是供体细胞中积累。我们发现,miR-451a被分选到外泌体中。然而,miR-451a在ESCC中的生物学功能仍不清楚。在此,我们进行了双荧光素酶报告实验,结果证明CAB39是miR-451a的靶基因。此外,从155个配对的ESCC组织和匹配组织的RNA测序数据中发现,CAB39与TGF-β1有关。Western Blot和qPCR显示,CAB39和TGF-β1在ESCC中呈正相关。将过表达 CAB39 的细胞与健康供血者的 PBMCs 进行共培养。流式细胞术检测表明,过度表达 CAB39 后凋亡细胞明显减少,而使用 TGF-β1 抑制剂后凋亡细胞明显增加。因此,我们的数据表明,CAB39 通过 TGF-β1 削弱了 ESCC 的抗肿瘤免疫力。综上所述,YWHAE可选择性地将miR-451a分选到外泌体中,并通过CAB39削弱抗肿瘤免疫促进肿瘤进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39

miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39

miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39
Exosomes are emerging mediators of cell-cell communication, which are secreted from cells and may be delivered into recipient cells in cell biological processes. Here, we examined microRNA (miRNA) expression in esophageal squamous cell carcinoma (ESCC) cells. We performed miRNA sequencing in exosomes and cells of KYSE150 and KYSE450 cell lines. Among these differentially expressed miRNAs, 20 of the miRNAs were detected in cells and exosomes. A heat map indicated that the level of miR-451a was higher in exosomes than in ESCC cells. Furthermore, miRNA pull-down assays and combined exosomes proteomic data showed that miR-451a interacts with YWHAE. Over-expression of YWHAE leads to miR-451a accumulation in the exosomes instead of the donor cells. We found that miR-451a was sorted into exosomes. However, the biological function of miR-451a remains unclear in ESCC. Here, Dual-luciferase reporter assay was conducted and it was proved that CAB39 is a target gene of miR-451a. Moreover, CAB39 is related to TGF-β1 from RNA-sequencing data of 155 paired of ESCC tissues and the matched tissues. Western Blot and qPCR revealed that CAB39 and TGF-β1 were positively correlated in ESCC. Over-expression of CAB39 were cocultured with PBMCs from the blood from healthy donors. Flow cytometry assays showed that apoptotic cells were significantly reduced after CAB39 over-expression and significantly increased after treated with TGF-β1 inhibitors. Thus, our data indicate that CAB39 weakens antitumor immunity through TGF-β1 in ESCC. In summary, YWHAE selectively sorted miR-451a into exosomes and it can weaken antitumor immunity promotes tumor progression through CAB39.
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来源期刊
Cancer gene therapy
Cancer gene therapy 医学-生物工程与应用微生物
CiteScore
10.20
自引率
0.00%
发文量
150
审稿时长
4-8 weeks
期刊介绍: Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.
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