Open AccessPU.1 attenuates TNF‑α‑induced proliferation and cytokine release of rheumatoid arthritis fibroblast‑like synoviocytes by regulating miR‑155 activity
Author(s) -
Z. Xie,
Youxing Qu,
Shen Peng-fei,
Bin Wang,
Kang Wei,
Bin Du
Publication year - 2018
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2018.8920
Subject(s) - foxo3 , competing endogenous rna , tumor necrosis factor alpha , downregulation and upregulation , cytokine , cancer research , microrna , three prime untranslated region , chemistry , fibroblast , transfection , biology , microbiology and biotechnology , messenger rna , untranslated region , immunology , long non coding rna , in vitro , biochemistry , gene
The present study aimed to determine the role of transcription factor PU.1 (PU.1) in tumor necrosis factor‑α (TNF‑α)‑induced proliferation and cytokine release of rheumatoid arthritis fibroblast‑like synoviocytes (RA‑FLS). It was determined that TNF‑α induced proliferation of RA‑FLS, whereas transfection with PU.1 3'untranslated region (UTR) inhibited this proliferation. Additionally, PU.1 3'UTR attenuated TNF‑α‑induced production of interleukin (IL)‑6 and IL‑1β, and downregulated the expression level of micro RNA (miR)‑155 in a dose‑dependent manner. Furthermore, transfection with PU.1 3'UTR significantly attenuated TNF‑α‑induced decrease in forkhead box protein O3 (FOXO3) expression level in RA‑FLS and these effects were consistent with the effects of miR‑155 inhibition. PU.1 and FOXO3 formed a competing endogenous RNA (ceRNA) network that regulated miR‑155 activity. In this competing endogenous RNA network, PU.1 3'UTR modulated FOXO3 expression in a miRNA‑ and 3'UTR‑dependent manner. Downregulation of FOXO3 expression reversed the PU.1 3'UTR‑mediated protective effects. Therefore, the results of the present study indicate that PU.1 3'UTR attenuates TNF‑α‑induced proliferation and cytokine release of RA‑FLS by acting as a ceRNA for FOXO3 to regulate miR‑155 activity.