PU.1 attenuates TNF‑α‑induced proliferation and cytokine release of rheumatoid arthritis fibroblast‑like synoviocytes by regulating miR‑155 activity

Xie,Zikang; Qu,Yuxing; Shen,Pengfei; Wang,Bin; Wei,Kang; Du,Bin

doi:10.3892/mmr.2018.8920

PU.1 attenuates TNF‑α‑induced proliferation and cytokine release of rheumatoid arthritis fibroblast‑like synoviocytes by regulating miR‑155 activity

Authors:
- Zikang Xie
- Yuxing Qu
- Pengfei Shen
- Bin Wang
- Kang Wei
- Bin Du
View Affiliations

Affiliations: Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China, Department of Orthopedics, Changzhou Traditional Chinese Medicine Hospital, Changzhou, Jiangsu 213003, P.R. China, Department of Orthopedics, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
Published online on: April 23, 2018 https://doi.org/10.3892/mmr.2018.8920
Pages: 8349-8356

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Dennis G Jr, Holweg CT, Kummerfeld SK, Choy DF, Setiadi AF, Hackney JA, Haverty PM, Gilbert H, Lin WY, Diehl L, et al: Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res Ther. 16:R902014. View Article : Google Scholar : PubMed/NCBI
2	Liu N, Feng X, Wang W, Zhao X and Li X: Paeonol protects against TNF-α-induced proliferation and cytokine release of rheumatoid arthritis fibroblast-like synoviocytes by upregulating FOXO3 through inhibition of miR-155 expression. Inflamm Res. 66:603–610. 2017. View Article : Google Scholar : PubMed/NCBI
3	Chang SK, Gu Z and Brenner MB: Fibroblast-like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin-11. Immunol Rev. 233:256–266. 2010. View Article : Google Scholar : PubMed/NCBI
4	Bartok B and Firestein GS: Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunol Rev. 233:233–255. 2010. View Article : Google Scholar : PubMed/NCBI
5	Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP: A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI
6	Li X, Zheng L, Zhang F, Hu J, Chou J, Liu Y, Xing Y and Xi T: STARD13-correlated ceRNA network inhibits EMT and metastasis of breast cancer. Oncotarget. 7:23197–23211. 2016.PubMed/NCBI
7	Zheng L, Li X, Gu Y, Lv X and Xi T: The 3′UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1. Breast Cancer Res Treat. 150:105–118. 2015. View Article : Google Scholar : PubMed/NCBI
8	Ma K, Zhao Q and Li S: Competing endogenous RNA network in pulmonary arterial hypertension. Int J Cardiol. 172:e527–e528. 2014. View Article : Google Scholar : PubMed/NCBI
9	Ge D, Han L, Huang S, Peng N, Wang P, Jiang Z, Zhao J, Su L, Zhang S, Zhang Y, et al: Identification of a novel MTOR activator and discovery of a competing endogenous RNA regulating autophagy in vascular endothelial cells. Autophagy. 10:957–971. 2014. View Article : Google Scholar : PubMed/NCBI
10	Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, et al: MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci USA. 108:11193–11198. 2011. View Article : Google Scholar : PubMed/NCBI
11	Alivernini S, Kurowska-Stolarska M, Tolusso B, Benvenuto R, Elmesmari A, Canestri S, Petricca L, Mangoni A, Fedele AL, Di Mario C, et al: MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis. Nat Commun. 7:129702016. View Article : Google Scholar : PubMed/NCBI
12	Lu D, Nakagawa R, Lazzaro S, Staudacher P, Abreu-Goodger C, Henley T, Boiani S, Leyland R, Galloway A, Andrews S, et al: The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation. J Exp Med. 211:2183–2198. 2014. View Article : Google Scholar : PubMed/NCBI
13	Huskova H, Korecka K, Karban J, Vargova J, Vargova K, Dusilkova N, Trneny M and Stopka T: Oncogenic microRNA-155 and its target PU.1: An integrative gene expression study in six of the most prevalent lymphomas. Int J Hematol. 102:441–450. 2015. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Zhang H, Wang F and Hu Y: STARD13 promotes hepatocellular carcinoma apoptosis by acting as a ceRNA for Fas. Biotechnol Lett. 39:207–217. 2017. View Article : Google Scholar : PubMed/NCBI
16	Wang Y and Lin G: TP53INP1 3′-UTR functions as a ceRNA in repressing the metastasis of glioma cells by regulating miRNA activity. Biotechnol Lett. 38:1699–1707. 2016. View Article : Google Scholar : PubMed/NCBI
17	Yang J, Li T, Gao C, Lv X, Liu K, Song H, Xing Y and Xi T: FOXO1 3′UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS Lett. 588:3218–3224. 2014. View Article : Google Scholar : PubMed/NCBI
18	Denzler R, Agarwal V, Stefano J, Bartel DP and Stoffel M: Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Mol Cell. 54:766–776. 2014. View Article : Google Scholar : PubMed/NCBI
19	Zhu J, Wang H, Chen J and Wei W: Inhibition of plasma kallikrein-kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis. Immunopharmacol Immunotoxicol. 40:134–148. 2018. View Article : Google Scholar : PubMed/NCBI
20	Xu J, Feng L, Han Z, Li Y, Wu A, Shao T, Ding N, Li L, Deng W, Di X, et al: Extensive ceRNA-ceRNA interaction networks mediated by miRNAs regulate development in multiple rhesus tissues. Nucleic Acids Res. 44:9438–9451. 2016.PubMed/NCBI