Download Aberrant expression of long non-coding RNA in T cells from patients

Aberrant expression of long non-coding RNAs in T cells from patients with
rheumatoid arthritis
Ming-Chi Lu1, Hui-Chun Yu1, Ning-Sheng Lai1
1
Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital,
Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan;
2
Department of Internal Medicine, National Taiwan University Hospital and National
Taiwan University College of Medicine, Taipei, Taiwan;
長片段非編碼核糖核酸在類風濕性關節炎的 T 細胞表現異常
呂明錡 1，游惠君 1，賴寧生 1
佛教慈濟醫療財團法人大林慈濟醫院過敏免疫風濕科1
Objective. We hypothesized the presence of aberrantly expressed long non-coding
ribonucleic acids (lncRNAs) that promote the T cell inflammatory responses in
patients with rheumatoid arthritis (RA).
Methods. The expression levels of ten potential aberrantly expressed lncRNAs were
evaluated in T cells from 39 patients with RA and 17 controls using real-time reverse
transcription-polymerase chain reaction. The aberrantly expressed lncRNAs were
measured in Jurkat cells co-cultured with or without ionomycin and phorbol
12-myristate 13-acetate. Transfection studies using small interfering RNA (siRNA)
were conducted for biological functions, and microarray analysis was performed to
search for target genes, of specific lncRNAs.
Results. We confirmed that the expression levels of LOC100652951 and
LOC100506036 were higher in T cells from RA patients compared with controls. RA
patients treated with biologic agents have lower expression levels of LOC100652951,
and female RA patients have lower LOC100506036 expression levels after
multivariate analysis. After activation, the expression levels of LOC100506036, but
not LOC100652951, increased in Jurkat cells. Transfection of siRNA targeting
LOC100506036 inhibited interferon gamma production and the expression of nuclear
factor of activated T cells in activated Jurkat cells. After the microarray analysis with
validation, inhibition of LOC100506036 expression by siRNA leaded to the decreased
expression of sphingomyelin phosphodiesterase 1 (SMPD1). The expression levels of
LOC100652951 in Jurkat cells did not changed after coculture with TNF-α.
Functional effect of LOC100652951 remain further investigation.
Conclusion: The expression levels of LOC100652951 and LOC100506036 were
increased in RA T cells. Treatment with biologic agents lowered the expression of
LOC100652951 in RA T cells. LOC100506036 regulated the expression of SMPD1
and NFAT1, contributing to inflammatory responses.