Exploring Long Non-Coding RNAs Associated with IP3/DAG Signaling Pathway as Potential Biomarkers Involved in Mast Cell Degranulation in Chronic Spontaneous Urticaria with 2-Year Follow-Up

Yudan Liang; Qinghuo Kong; Huiwen Luo; Jinhua Tan; Huizheng Zhu

doi:10.2147/JIR.S343826

Exploring Long Non-Coding RNAs Associated with IP3/DAG Signaling Pathway as Potential Biomarkers Involved in Mast Cell Degranulation in Chronic Spontaneous Urticaria with 2-Year Follow-Up

J Inflamm Res. 2022 Jan 14:15:267-283. doi: 10.2147/JIR.S343826. eCollection 2022.

Authors

Yudan Liang^#^{1

2}, Qinghuo Kong^#¹, Huiwen Luo¹, Jinhua Tan¹, Huizheng Zhu³

Affiliations

¹ Department of Acupuncture and Rehabilitation, The Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan University, Jiangmen, Guangdong, People's Republic of China.
² Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong, People's Republic of China.
³ Department of Traditional Chinese Medicine, The 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, Guangdong, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Chronic spontaneous urticaria (CSU) pathogenesis involves mast cell degranulation induced by the inositol 1,4,5-trisphosphate/diacylglycerol (IP3/DAG) pathway, but the condition lacks specific biomarkers. This study was performed to investigate long non-coding RNA (lncRNA) expression profiles, identify those associated with IP3/DAG pathway, and assess their diagnostic and prognostic value for CSU.

Methods: Ten samples were selected from CSU and control groups, and microarray was performed to screen differentially expressed (DE) lncRNAs and mRNAs. Bioinformatic and co-expression network analyses were used to identify lncRNAs associated with IP3/DAG pathway. Quantitative real-time polymerase chain reaction was used to validate lncRNA expression levels. Combined with disease characteristics and serum indices detected with enzyme-linked immunosorbent assays, Spearman analysis and logistic regression were applied to analyze lncRNA-associated disease risk. Receiver operating characteristic (ROC) curves and 2-year follow-up data were applied to evaluate lncRNA diagnostic and prognostic value.

Results: A total of 678 up- and 573 downregulated DE lncRNAs and 609 up- and 176 downregulated DE mRNAs were identified. Seven lncRNAs (upregulated T264761, T280622, ENST00000587970, T224062, ENST00000562459, and his-1_RNA_dna; downregulated ENST00000417930) were associated with the IP3/DAG pathway. D-dimer and histamine levels were significantly different between the two groups. Correlation analysis showed that his-1_RNA_dna positively correlated with the frequency of symptom appearance, while his-1_RNA_dna, ENST00000417930, T264761, and T280622 negatively correlated with the maximum wheal diameter. Regression analysis showed T264761 was associated with CSU risk. ROC analysis showed that the specificity of T264761 was 90%, with an area under the curve of 0.666. In follow-up, the rate of well-controlled disease in the low T264761 expression group was 82.61%.

Conclusion: This study established lncRNA and mRNA expression profiles in CSU and identified lncRNAs associated with IP3/DAG pathway, which is mechanistically involved in this disease. T264761 may be a novel biomarker for CSU, but further study is needed to confirm its specific mechanism.

Keywords: biomarker; lncRNA; mRNA; microarray; urticaria.

Grants and funding

This study was jointly funded by grants from the National Natural Science Foundation of China (81804176,81904074), the China Postdoctoral Science Foundation (2017M622919, 2018M631049), the Natural Science Foundation of Guangdong Province of China (2020A1515011421), and the Project of Administration of Traditional Chinese Medicine of Guangdong Province of China (20191369, 20201380).