Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients’ platelets

Wang，Tingting1,2; Meng，Shuhui1; Chen，Ping1; Wei，Laiyou5,6; Liu，Cuilian1,5; Tang，Donge1,4; Liu，Dongzhou1,5; Jiang，Zhenyou3; Hong，Xiaoping1,2,5

2021-12-01

10.1016/j.yexcr.2021.112895

EXPERIMENTAL CELL RESEARCH   影响因子和分区

0014-4827

1090-2422

Ankylosing spondylitis (AS) is a chronic inflammatory disease significantly decreasing the quality of life. Platelets play an important and active role in the development of AS. Accumulating evidence demonstrated platelets contain diverse RNA repository inherited from megakaryocytes or microvesicles. Platelet RNAs are dynamically affected by pathological conditions and could be used as diagnostic or prognostic biomarkers. However, the role of the platelet RNAs in AS is elusive. In this study, we compared mRNA and circRNA profiles in platelets between AS patients and healthy controls using RNA sequencing and bioinformatic analysis, and found 4996 mRNAs and 2942 circRNAs were differently expressed. The significantly over-expressed mRNAs in AS patients are involved in platelet activity, gap junction, focal adhesion, rap1 and toll and Imd signaling pathway. The previous identified platelet-derived immune mediators such as P2Y1, P2Y12, PF4, GPIbα, CD40L, ICAM2, CCL5 (RANTES), TGF-β (TGF-β1 and TGF-β2) and PDGF (PDGFB and PDGFA) are also included in these over expressed mRNAs, implying these factors may trigger inflammatory cascades and promote the development of AS. Additionally, we found two down-regulated circRNA (circPTPN22 and circFCHSD2) from the intersection analyses of platelets and spinal ligament tissues of AS patients. The circRNA-miRNA-mRNA regulatory network of these two circRNAs was constructed, and the target mRNAs were enriched in Th17 cell differentiation, inflammatory bowel disease, cell adhesion molecules, cytokine-cytokine receptor interaction, Jak-STAT and Wnt signaling pathway, all these pathways participate in the bone remodeling and pro/anti-inflammatory immune regulation in AS. Then, qRT-PCR was performed to validate the expression of selected key mRNAs and circRNAs and the results demonstrated that the expression levels of P2Y12, GPIbα, circPTPN22 and circFCHSD2 were consistent with the sequencing analysis. In addition, the high expression of five predicted miRNAs interacting with circPTPN22 and circFCHSD2 were also detected in AS by qRT-PCR. Taken together, our study presents a comprehensive overview of mRNAs and circRNAs in platelets in AS patients and offers new insight into the mechanisms of platelet involving in the pathogenesis of AS. The mRNAs and circRNAs identified in this study may serve as candidates for diagnosis and targeted treatment of AS.

Ankylosing spondylitis CircRNA-miRNA-mRNA regulatory network Circular RNA mRNA Platelet

SCI

英语

通讯

Shenzhen Key Medical Discipline Construction Fund[SZXK011] ; science and technology plan of Shenzhen[JCYJ20200109144218597] ; Shenzhen Health Plan Committee Research Foundation[SZFZ2018021]

Oncology ; Cell Biology

Oncology ; Cell Biology

WOS:000724653600002

ELSEVIER INC

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85118591690

Scopus

1.Department of Rheumatology and Immunology,The Second Clinical Medical College,Jinan University (Shenzhen People's Hospital),Shenzhen,518020,China
2.Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou,510632,China
3.Department of Microbiology and Immunology,College of Basic Medicine and Public Hygiene,Jinan University,Guangzhou,510632,China
4.Department of Clinical Medical Research Center,The Second Clinical Medical College,Jinan University (Shenzhen People's Hospital),Shenzhen,518020,China
5.Shenzhen People's Hospital,The Frist Affiliated Hospital of Southern University of Science and Technology,Shenzhen,518020,China
6.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Wang，Tingting,Meng，Shuhui,Chen，Ping,等. Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients’ platelets[J]. EXPERIMENTAL CELL RESEARCH,2021,409(1).

Wang，Tingting.,Meng，Shuhui.,Chen，Ping.,Wei，Laiyou.,Liu，Cuilian.,...&Hong，Xiaoping.(2021).Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients’ platelets.EXPERIMENTAL CELL RESEARCH,409(1).

Wang，Tingting,et al."Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients’ platelets".EXPERIMENTAL CELL RESEARCH 409.1(2021).