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1 型糖尿病相关 circRNAs 调节 CD4+ T 细胞功能。

Type 1 Diabetes Mellitus-Related circRNAs Regulate CD4+ T Cell Functions.

机构信息

Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000 Shandong, China.

Department of Pharmacy, Army Medical University, Chongqing 400038, China.

出版信息

Biomed Res Int. 2022 Aug 24;2022:4625183. doi: 10.1155/2022/4625183. eCollection 2022.

Abstract

Circular RNAs (circRNAs) participate in development of malignancies through its active role as a "miRNA sponge." Their roles in type 1 diabetes mellitus (T1DM) pathogenesis are elusive. Here, the important role of circRNAs in T1DM was explored. circRNA profiling was performed for isolated CD4+ T cells from blood of T1DM and healthy volunteers. There were 257 differentially expressed circRNAs. Only three upregulated DEcircRNAs (hsa_circ_0000324, hsa_circ_0001853, and hsa_circ_0068797) were consistent with the GEO database. Through KEGG analyses, it was found that the three DEcircRNAs were associated with 11 miRNAs and 8 immune-related target genes (mRNA). Further analysis found that four miRNAs, two circRNAs, and four mRNAs were associated with nine circRNA-miRNA-mRNA networks. This confirmed the requirements of sponge mechanisms. The qRT-PCR analysis revealed that circRNA000324/miRNA675-5p/MAPK14 and circRNA000324/miRNA-675-5p/SYK may be potential mechanisms in regulation of differentiation and proliferation of CD4+ T cell in patients with T1DM. Therefore, targeting circRNA to regulate cellular immune responses by regulating CD4+ T cell differentiation may be a new strategy for the treatment of T1DM.

摘要

环状 RNA(circRNAs)通过作为“miRNA 海绵”的积极作用参与恶性肿瘤的发生。它们在 1 型糖尿病(T1DM)发病机制中的作用尚不清楚。本文探讨了 circRNAs 在 T1DM 中的重要作用。对来自 T1DM 和健康志愿者血液的分离的 CD4+T 细胞进行 circRNA 谱分析。有 257 个差异表达的 circRNAs。只有三个上调的 DEcircRNAs(hsa_circ_0000324、hsa_circ_0001853 和 hsa_circ_0068797)与 GEO 数据库一致。通过 KEGG 分析,发现这三个 DEcircRNAs 与 11 个 miRNA 和 8 个免疫相关的靶基因(mRNA)有关。进一步分析发现,四个 miRNA、两个 circRNAs 和四个 mRNAs 与九个 circRNA-miRNA-mRNA 网络有关。这证实了海绵机制的要求。qRT-PCR 分析显示,circRNA000324/miRNA675-5p/MAPK14 和 circRNA000324/miRNA-675-5p/SYK 可能是 T1DM 患者 CD4+T 细胞分化和增殖调节的潜在机制。因此,通过调节 CD4+T 细胞分化来靶向 circRNA 调节细胞免疫反应可能是治疗 T1DM 的一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae7f/9433285/7d0a60c1bee0/BMRI2022-4625183.001.jpg

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