LncRNA OIP5-AS1 promotes immune evasion in abdominal aortic aneurysm cells by recruiting MDSCs and inhibiting CD8 + T cells through STK24 upregulation.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2025-06-01 Epub Date: 2025-05-15 DOI:10.1007/s10616-025-00767-x

Baoping Deng, Qili Liu, Qingqing Xiao, Minjie Yang, Xiaoyong Ge, Jiacong Weng, Hongmei Zheng, Weiping Deng

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引用次数: 0

Abstract

This study aims to investigate the expression and immune function of long non-coding RNA OIP5-AS1 (OIP5-AS1) and Serine/Threonine Kinase 24 (STK24) in abdominal aortic aneurysm (AAA). An animal model of AAA was established, along with cell models for overexpression and underexpression of OIP5-AS1 and STK24. Histological staining, qPCR, enzyme-linked immunosorbent assay (ELISA), Cell Counting Kit-8 assay, western blotting, RNA immunoprecipitation (RIP) analysis, and flow cytometry were employed to assess their effects on inflammation, cell proliferation, and apoptosis. In this study, Immunohistochemistry and qPCR analyses revealed significant upregulation of OIP5-AS1 and STK24 in both AAA tissue samples as well as cell models. ELISA demonstrated that elevated levels of OIP5-AS1 and STK24 significantly enhanced the secretion of inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ), promoted cell proliferation while inhibiting apoptosis. RIP analysis combined with RNA pull-down assays indicated that OIP5-AS1 binds to the promoter region of STK24 by recruiting Zinc Finger Protein 93 (ZNF93) transcription factor leading to increased transcriptional expression of STK24. Furthermore, it was found that the functional role played by OIP5-AS1/STK24 axis operates through the AKT pathway. Increased expression levels of either OIP5-SAI or STK24 facilitated myeloid- derived suppressor cells (MDSCs) migration while suppressing CD8 + T-cell activity. The findings from this study highlight the critical involvement of the OIP5-SAI/STK24 axis in AAA progression by promoting MDSCs migration while inhibiting CD8 + T-cell activity. These insights provide novel perspectives into understanding the molecular pathology underlying AAA development while identifying potential therapeutic targets.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00767-x.

查看原文本刊更多论文

LncRNA OIP5-AS1通过STK24上调募集MDSCs和抑制CD8 + T细胞，促进腹主动脉瘤细胞的免疫逃避。

本研究旨在探讨长链非编码RNA OIP5-AS1 （OIP5-AS1）和丝氨酸/苏氨酸激酶24 （STK24）在腹主动脉瘤（AAA）中的表达及其免疫功能。建立AAA动物模型，同时建立OIP5-AS1和STK24过表达和过表达细胞模型。采用组织学染色、qPCR、酶联免疫吸附法（ELISA）、细胞计数试剂盒（Cell Counting Kit-8）、western blotting、RNA免疫沉淀（RIP）分析和流式细胞术评估其对炎症、细胞增殖和凋亡的影响。在本研究中，免疫组织化学和qPCR分析显示，在AAA组织样本和细胞模型中，OIP5-AS1和STK24均显著上调。ELISA结果显示，OIP5-AS1和STK24水平升高可显著增强炎性细胞因子（IL-1β、IL-6、TNF-α和IFN-γ）的分泌，促进细胞增殖，抑制细胞凋亡。RIP分析结合RNA pull-down实验表明，OIP5-AS1通过募集锌指蛋白93 （ZNF93）转录因子结合STK24的启动子区，导致STK24的转录表达增加。此外，我们还发现OIP5-AS1/STK24轴通过AKT通路发挥功能作用。OIP5-SAI或STK24表达水平的增加促进髓源性抑制细胞（MDSCs）迁移，同时抑制CD8 + t细胞活性。这项研究的结果强调了OIP5-SAI/STK24轴通过促进MDSCs迁移同时抑制CD8 + t细胞活性参与AAA进展的关键作用。这些见解为了解AAA发展的分子病理学基础提供了新的视角，同时确定了潜在的治疗靶点。补充信息：在线版本包含补充资料，可在10.1007/s10616-025-00767-x获得。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.