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Immunology. 2018 Sep;155(1):137-149. doi: 10.1111/imm.12940. Epub 2018 May 23.

Circular RNA expression profile and potential function of hsa_circ_0045272 in systemic lupus erythematosus.

Li LJ1,2, Zhu ZW1,2, Zhao W1,2, Tao SS1,2, Li BZ1,2, Xu SZ1,2, Wang JB1,2, Zhang MY1,2,3, Wu J1,2, Leng RX1,2, Fan YG1,2, Pan HF1,2, Ye DQ1,2.

Author information

1
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
2
Anhui Province Key Laboratory of Major Autoimmune Diseases, Hefei, Anhui, China.
3
Department of Medical Record Room, Affiliated Fuyang Hospital of Anhui Medical University, Fuyang, China.

Abstract

Circular RNAs (circRNAs) represent a class of non-coding RNAs that form covalently closed RNA circles with extensive expression and conservation in mammals. Circular RNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases, but studies of circRNA role in systemic lupus erythematosus (SLE) are lacking. The present study measured the circRNA expression profiles in T cells from patients with SLE and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients. Down-regulation of hsa_circ_0045272 in SLE T cells was verified with quantitative PCR. Jurkat cells with stable hsa_circ_0045272 knockdown were generated using specific lentiviral short hairpin RNA for functional studies. Flow cytometric analysis indicated that hsa_circ_0045272 knockdown significantly up-regulated the early apoptosis of Jurkat cells. Meanwhile, ELISA showed that hsa_circ_0045272 knockdown significantly enhanced interleukin-2 production of activated Jurkat cells. Then, ceRNAs were predicted for hsa_circ_0045272 and the significant down-regulation of two mRNAs predicted as ceRNAs, NM_003466 (PAX8) and NM_015177 (DTX4), but not their corresponding proteins, was validated. Furthermore, dual luciferase reporter assay indicated binding of hsa_circ_0045272 with hsa-miR-6127. Circular RNA-mRNA co-expression networks showed the correlation of circRNAs with mRNAs and provided additional clues to circRNA functions. Our study demonstrated dysregulated circRNAs in SLE and revealed the function of hsa_circ_0045272 in negatively regulating apoptosis and interleukin-2 secretion and its potential mechanism. The implication of hsa_circ_0045272 and other abnormal circRNAs in SLE merits further investigation.

KEYWORDS:

circular RNA; competitive endogenous RNA; non-coding RNA; systemic lupus erythematosus

PMID:
29700819
PMCID:
PMC6099170
DOI:
10.1111/imm.12940
[Indexed for MEDLINE]

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