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吲哚胺 2,3-双加氧酶的抗肿瘤短发夹 RNA 体内递送后脾细胞和中性粒细胞中 mRNA 和 tRNA 基因的表达谱

The Expression Profile of mRNA and tRNA Genes in Splenocytes and Neutrophils after In Vivo Delivery of Antitumor Short Hairpin RNA of Indoleamine 2,3- Dioxygenase.

机构信息

Department of Internal Medicine, E-DA Cancer Hospital, Kaohsiung 840, Taiwan.

School of Medicine, I-Shou University, Kaohsiung 840, Taiwan.

出版信息

Int J Mol Sci. 2020 Sep 13;21(18):6703. doi: 10.3390/ijms21186703.

Abstract

RNA-based therapeutics are considered as novel treatments for human diseases. Our previous study demonstrated that treatment with short-hairpin RNA against (IDO shRNA) suppresses tumor growth, detects Th1-bias immune responses, and elevates expression of tryptophan transfer RNA (tRNA) in total splenocytes. In addition, depletion of Ly6g neutrophils attenuates the effect of IDO shRNA. The aim of this study was to investigate the regulatory network and the expression profile of tRNAs and other non-coding RNAs in IDO shRNA-treated spleens. The total splenocytes and magnetic bead-enriched splenic neutrophils were collected from the lung tumor bearing mice, which were treated with IDO shRNA or scramble IDO shRNA, and the collected cells were subsequently subjected to RNA sequencing. The gene ontology analysis revealed the different enrichment pathways in total splenocytes and splenic neutrophils. Furthermore, the expression of tRNA genes was identified and validated. Six isoacceptors of tRNA, with different expression patterns between total splenocytes and splenic neutrophils, were observed. In summary, our findings not only revealed novel biological processes in IDO shRNA-treated total splenocytes and splenic neutrophils, but the identified tRNAs and other non-coding RNAs may contribute to developing a novel biomarker gene set for evaluating the clinical efficiency of RNA-based cancer immunotherapies.

摘要

基于 RNA 的疗法被认为是人类疾病的新型治疗方法。我们之前的研究表明,用短发夹 RNA (IDO shRNA)治疗可抑制肿瘤生长,检测到 Th1 偏向性免疫反应,并提高总脾细胞中色氨酸转移 RNA (tRNA)的表达。此外,Ly6g 中性粒细胞的耗竭会减弱 IDO shRNA 的作用。本研究旨在探讨 IDO shRNA 处理的脾脏中 tRNA 和其他非编码 RNA 的调控网络和表达谱。从携带肺肿瘤的小鼠中收集总脾细胞和磁珠富集的脾中性粒细胞,用 IDO shRNA 或对照 IDO shRNA 处理,然后将收集的细胞进行 RNA 测序。基因本体分析显示总脾细胞和脾中性粒细胞中不同的富集途径。此外,还鉴定和验证了 tRNA 基因的表达。观察到总脾细胞和脾中性粒细胞中六种 tRNA 同功受体的表达模式不同。总之,我们的研究结果不仅揭示了 IDO shRNA 处理的总脾细胞和脾中性粒细胞中的新生物学过程,而且鉴定的 tRNA 和其他非编码 RNA 可能有助于开发用于评估基于 RNA 的癌症免疫疗法临床疗效的新型生物标志物基因集。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc95/7555719/260a7e11abc8/ijms-21-06703-g001.jpg

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