The Role of lncRNA AF117829.1 in the Immunological Pathogenesis of Severe Aplastic Anaemia

Abstract

Objective. Severe aplastic anaemia (SAA) is an autoimmune disease with immune tolerance dysfunction mediated by hyperactivated T lymphocytes that target the haematopoietic system. Numerous studies suggest that long noncoding RNAs (lncRNAs) play a significant role in almost every level of gene function/regulation. However, their specific mechanisms in SAA remain undetermined. This study is aimed at determining the role of key lncRNAs in CD8+ T lymphocytes in the mechanisms of SAA. Methods. RNA-seq was performed to detect all lncRNAs and mRNAs in peripheral CD8+ T lymphocytes from SAA patients and healthy controls. The lncRNA targets were predicted by bioinformatics, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RT-qPCR was used to verify the expression of key lncRNAs and their predicted targets. We screened lncRNA AF117829.1, which was correlated with autoimmune diseases and downregulated in CD8+ T lymphocytes, and further validated its effects on CD8+ T lymphocytes from SAA patients. Results. We systematically described the lncRNA/mRNA expression changes in CD8+ T lymphocytes in SAA patients and assessed their possible biological functions and signalling pathways. A total of 194 lncRNAs and 2099 mRNAs were changed in SAA patients versus healthy controls. These differentially expressed lncRNAs/mRNAs were associated with organelle components, catalytic activity, the response to stimulation, signal transduction, the immune system and metabolic processes. The downregulated expression of one altered factor, lncRNA AF117829.1, in CD8+ T lymphocytes from SAA patients increased CD8+ T lymphocyte immune function by promoting RIP2 expression. lncRNA AF117829.1 overexpression in CD8+ T lymphocytes reduced perforin and granzyme B expression. The same effect was achieved with GSK583, a RIP2 kinase inhibitor. Conclusions. The proliferation and overactivation of CD8+ T lymphocytes, also known as cytotoxic T cells (CTLs), directly induce bone marrow (BM) failure in SAA patients, but the specific mechanism remains unclear. We found that lncRNA AF117829.1 and its target genes were associated with T cell proliferation, differentiation, and immune dysregulation and that lncRNA AF117829.1 regulated CD8+ T lymphocyte function in SAA patients by promoting RIP2 expression. These findings improve our understanding of the molecular mechanism of immune pathogenesis and provide potential targets for SAA diagnosis and treatment.

A Prognostic Pyroptosis-Related lncRNAs Risk Model Correlates With the Immune Microenvironment in Colon Adenocarcinoma

“…In bone metastatic melanoma, AL118506.1 (antisense to abhydrolase domain containing 16B) participates in the ceRNA network of has-miR-27b-3p/AL118506.1/THBS2, which has great utility in predicting survival and metastasis of melanoma ( Huang et al, 2019 ). In severe aplastic anemia (SAA) patients, the decreased expression of AF117829.1 upregulates the activity of CD8 + T lymphocytes, which means lncRNA may be associated with the regulation of the immune microenvironment ( Li et al, 2021 ). POC1B-AS1 is also a risk factor in the prognostic model of endometrial carcinoma ( Liu J. et al, 2021 ).…”

Machine Learning Gene Signature to Metastatic ccRCC based on ceRNA Network

“…The lncRNA AF11782.1 mechanism of action remains unknown but was related to the proliferation, differentiation, and regulation of the immunity of T cells [68,69], and as presented earlier, his expression was found to be related to metastatic development and worst prognosis of ccRCC patients, indicating new actions within the cancer field of studies. At this cluster, due to the high level of expression, a sponge act could be existing where the miRNA doesn't degrade the POLE2 and HMMR, promoting cell differentiation and metastasis development.…”

Machine Learning Gene Signature to Metastatic ccRCC Based on ceRNA Network

“…The Hyaluronan Mediated Motility Receptor (HMMR) is responsible for the regulation of tumor cell motility [51], and its knockdown reduced peritoneal metastasis in gastric cancer [52]. The role of lncRNA AF117829.1 remains unknown, but it was described as related to the proliferation, differentiation, and regulation of T-cell immunity [53,54], and its expression is implied with metastatic development and the worst prognosis of ccRCC patients. In this context, the lncRNA AF117829.1 could be acting as a sponge over the miRNA, impairing the degradation of POLE2 and HMMR, and promoting cell differentiation and metastasis development.…”