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Int J Mol Med. 2016 Nov;38(5):1507-1514. doi: 10.3892/ijmm.2016.2755. Epub 2016 Sep 28.

Quercetin promotes the apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis by upregulating lncRNA MALAT1.

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Department of Rheumatology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, P.R. China.
Department of Renal Diseases, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, P.R. China.


Rheumatoid arthritis (RA) is a chronic autoimmune joint disease and fibroblast-like synoviocytes (FLS) are the resident mesenchymal cells of synovial joints. Quercetin is a dietary antioxidant. In this study, we aimed to explore the mechanisms responsible for the quercetin-induced apoptosis of FLS from patients with RA (termed RAFLS). RAFLS viability was determined following treatent of the cells with or without quercetin using the Cell Counting kit-8 (CCK-8) assay. The apoptosis of the RAFLS was analyzed using the Annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit I. The results revealed that RAFLS viability decreased and apoptosis increased in following treatment with quercetin. The differentially expressed long non-coding RNAs (lncRNAs) were screened and marked by PCR array following treatment with quercetin. The expression levels of the screened lncRNAs were then determined and compared in the cells treated with or without quercetin by quantitative PCR. The lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was finally selected. Small interfering RNA (siRNA) was then used to knock down the expression of MALAT1 in order to determine the role of MALAT1 in the quercetin-induced apoptosis of RAFLS. The results revealed that the knockdown of MALAT1 inhibited RAFLS apoptosis. At the same time, the expression of caspase-3 and caspase-9 was significantly decreased in the cells in which MALAT1 was knocked down. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was activated; this activation is known to be associated with enhanced cell proliferation and decreased apoptosis. The findings of our study indicate that quercetin promotes RAFLS apoptosis by upregulating lncRNA MALAT1, and that MALAT1 induces apoptosis by inhibiting the activation of the PI3K/AKT pathway.

[Indexed for MEDLINE]

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