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

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.

Changed cellular functions and aberrantly expressed miRNAs and circRNAs in bone marrow stem�cells in osteonecrosis of the femoral head

“…Thus, it was speculated that the dE circRNAs or miRNAs associated with blood loss could also be correlated with ONFH. Third, the dE circRNAs and miRNAs might also result from the autoimmune diseases such as SLE instead of ONFH, which has been demonstrated in previous studies (44)(45)(46). It is true that SLE itself could lead to DE miRNAs and circRNAs.…”

Long Noncoding RNAs and Circular RNAs in Autoimmune Diseases

“…Among those identified, decreased circ_0045272 expression was observed in T cells from SLE patients. Downregulation of the circ_0045272 in Jurkat cells induced early apoptosis and significantly enhanced IL-2 production [ 60 ], features of SLE onset.…”

Circular RNAs and Their Emerging Roles in Immune Regulation

“…They found hsa_circ_0045272 to be downregulated significantly. Furthermore, they demonstrated that hsa_circ_0045272 regulated apoptosis and IL-2 production negatively (89). However, the mechanisms underlying the involvement of hsa_circ_0045272 in SLE pathogenesis merits further exploration.…”