Identification of PRKCQ-AS1 as a Keratinocyte-Derived Exosomal lncRNA That Promotes Th17 Differentiation and IL-17 secretion in Psoriasis Through Bioinformatics, Machine Learning Algorithms, and Cell Experiments
Pengfei Gao,1,2 Xiaolu Gao,3 Long Lin,1 Ming Zhang,1,2 Dongqiang Luo,4 Chuyan Chen,1 Yujie Li,1 Yufeng He,1 Xianmiao Liu,1 Chunyu Shi,1 Ruisi Yang1 1School of Yunkang Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 2Biomedical Big Data Center, Nanfang College, Guangzhou,...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-05-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/identification-of-prkcq-as1-as-a-keratinocyte-derived-exosomal-lncrna--peer-reviewed-fulltext-article-JIR |
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| Summary: | Pengfei Gao,1,2 Xiaolu Gao,3 Long Lin,1 Ming Zhang,1,2 Dongqiang Luo,4 Chuyan Chen,1 Yujie Li,1 Yufeng He,1 Xianmiao Liu,1 Chunyu Shi,1 Ruisi Yang1 1School of Yunkang Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 2Biomedical Big Data Center, Nanfang College, Guangzhou, People’s Republic of China; 3The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Pengfei Gao, School of Yunkang Medicine and Health, Nanfang College, Guangzhou, China; Biomedical Big Data Center, Nanfang College, Guangzhou, People’s Republic of China, Email gaopf@nfu.edu.cnBackground: Psoriasis is an immune-mediated skin disease where Th17 cell differentiation and IL-17 secretion play critical roles. This study investigates key exosomal ncRNAs regulating the Th17/IL-17 axis in psoriasis and their mechanisms.Methods: We integrated bulk RNA sequencing datasets from the GEO database to construct and evaluate exosome-related patterns. Subsequently, exosome-related ncRNAs in psoriasis lesions were identified primarily through weighted gene co-expression network analysis and five machine learning algorithms. Additionally, large-scale integrated single-cell RNA sequencing data and genome-wide association study (GWAS) data were included to investigate the mechanisms of key ncRNA, primarily through immune infiltration analysis, gene set enrichment analysis (GSEA), co-expression analysis, and Mendelian randomization. Finally, the mechanisms of key ncRNA were confirmed primarily through cell co-culture and lentiviral transfection, assessed by immunofluorescence, qRT-PCR, and Western blot.Results: We identified 10 exosome-related ncRNAs, including PRKCQ-AS1, and constructed five machine learning models with excellent diagnostic performance, emphasizing PRKCQ-AS1’s significance. Mendelian randomization demonstrated a causal relationship between PRKCQ-AS1 and psoriasis. Immune infiltration analysis and GSEA indicated that PRKCQ-AS1 influences the infiltration pattern of CD4+T cells, promotes Th17 differentiation, and is related to STAT3. The expression distribution in single-cell RNA sequencing data suggested that exosomal PRKCQ-AS1 may originate from keratinocytes, and co-expression analysis supported its role in STAT3 activation within lymphocytes. Co-culture experiments confirmed that keratinocytes in psoriasis models, as well as keratinocytes overexpressing PRKCQ-AS1, can upregulate PRKCQ-AS1 levels in CD4+T cells via exosomes, promoting Th17 cell differentiation and IL-17 secretion. Consistent results and STAT3 signaling pathway activation were detected in CD4+T cells overexpressing PRKCQ-AS1.Conclusion: PRKCQ-AS1 is an exosomal lncRNA from keratinocytes in psoriasis, promoting Th17 differentiation and IL-17 secretion through STAT3 activation. This finding deepens the understanding of psoriasis pathogenesis and provides a basis for targeted therapies. Keywords: psoriasis, exosomes, Th17, PRKCQ-AS1, pathogenesis, bioinformatics |
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| ISSN: | 1178-7031 |