AUTHOR=Tan Yejun , Tang Wang , Xiao Wenbiao , Huang Roujie , Li Xin , Peng Weijun , Yan Kuipo , Cao Yuan , Zeng Yi , Kang Jin 

TITLE=lncRNA-associated ceRNA network revealing the potential regulatory roles of ferroptosis and immune infiltration in Alzheimer’s disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1105690

DOI=10.3389/fnagi.2023.1105690

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>Alzheimer’s disease (AD) is the most common form of dementia characterized by a prominent cognitive deterioration of sufficient magnitude to impair daily living. Increasing studies indicate that non-coding RNAs (ncRNAs) are involved in ferroptosis and AD progression. However, the role of ferroptosis-related ncRNAs in AD remains unexplored.</p></sec><sec><title>Methods</title><p>We obtained the intersection of differentially expressed genes in GSE5281 (brain tissue expression profile of patients with AD) from the GEO database and ferroptosis-related genes (FRGs) from the ferrDb database. Least absolute shrinkage and selection operator model along with weighted gene co-expression network analysis screened for FRGs highly associated with AD.</p></sec><sec><title>Results</title><p>A total of five FRGs were identified and further validated in GSE29378 (area under the curve = 0.877, 95% confidence interval = 0.794–0.960). A competing endogenous RNA (ceRNA) network of ferroptosis-related hub genes (<italic>EPT1</italic>, <italic>KLHL24</italic>, <italic>LRRFIP1</italic>, <italic>CXCL2</italic> and <italic>CD44</italic>) was subsequently constructed to explore the regulatory mechanism between hub genes, lncRNAs and miRNAs. Finally, CIBERSORT algorithms were used to unravel the immune cell infiltration landscape in AD and normal samples. M1 macrophages and mast cells were more infiltrated whereas memory B cells were less infiltrated in AD samples than in normal samples. Spearman’s correlation analysis revealed that LRRFIP1 was positively correlated with M1 macrophages (<italic>r</italic> = -0.340, <italic>P</italic> &lt; 0.001) whereas ferroptosis-related lncRNAs were negatively correlated with immune cells, wherein miR7-3HG correlated with M1 macrophages and <italic>NIFK-AS1</italic>, <italic>EMX2OS</italic> and <italic>VAC14-AS1</italic> correlated with memory B cells (|<italic>r</italic>| &gt; 0.3, <italic>P</italic> &lt; 0.001).</p></sec><sec><title>Conclusion</title><p>We constructed a novel ferroptosis-related signature model including mRNAs, miRNAs and lncRNAs, and characterized its association with immune infiltration in AD. The model provides novel ideas for the pathologic mechanism elucidation and targeted therapy development of AD.</p></sec>