miR-338-5p Regulates the Viability, Proliferation, Apoptosis and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting NFAT5

Guo, Ting; Ding, Hao; Jiang, Hui; Bao, Nirong; Zhou, Lei; Zhao, Jianning

doi:10.1159/000493222

Cited by 28 publications

(15 citation statements)

References 40 publications

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“…The molecular functions of this gene include DNA binding and transcription of downstream targets in response to stimulations, such as hypertonic stress and proinflammatory and hypoxic stimuli (Johnson et al 2016;Choi et al 2017). Nfat5 was mainly reported to be expressed in kidney cells, immune cells, muscle cells, and synoviocytes (Burg et al 1997;O'Connor et al 2006;Boland et al 2015;Choi et al 2017;Guo et al 2018). Limited knowledge is available about the expression pattern and function of Nfat5 in hard tissues.…”

Section: Discussionmentioning

confidence: 99%

MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation

et al. 2019

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The development of periodontal tissue is a complex process, including cementoblast proliferation and differentiation. Emerging reports suggest that microRNAs (miRNAs) play crucial roles in gene regulatory networks governing numerous biological processes. However, how miRNAs modulate cementoblast proliferation and differentiation remains largely unknown. In a previous study, we performed miRNA microarray profiling to fully reveal the expression patterns of miRNAs involved in cementoblast differentiation. We focused on miR-361-3p, which decreased during cementoblast differentiation. Overexpression of miR-361-3p resulted in decreased cementoblast differentiation, whereas the functional inhibition of miR-361-3p yielded the opposite effect. The bioinformatics approach identified nuclear factor of activated T-cell 5 ( Nfat5) as a potential target of miR-361-3p, which was further verified by dual luciferase assay. Meanwhile, the expression pattern of Nfat5 was verified both in vitro and in vivo. Furthermore, knockdown of Nfat5 mimicked the inhibitory effect of overexpressing miR-361-3p in cementoblasts. Moreover, multiple signaling pathways, including the Erk1/2, JNK, p38, PI3K-Akt, and NF-κB pathways, were notably activated, and the Wnt/ß-catenin pathway was blocked by downregulation of Nfat5 or forced expression of miR-361-3p in cementoblast differentiation. Finally, the complementary approach demonstrated that miR-361-3p regulated cementoblast differentiation via or partially via Erk1/2 and PI3K-Akt. Overall, our study elucidated that the JNK, p38, NF-κB, and Wnt/ß-catenin pathways act as balancing players in the miR-361-3p/ Nfat5 signaling axis during cementoblast differentiation.

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Section: Discussionmentioning

confidence: 99%

MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation

et al. 2019

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“…Although miRNAs do not encode protein products, they may modulate gene expression at the post-transcriptional level via interacting with the 3'-UTR of target mRNAs (29,37). For instance, miR-338-5p promotes cell viability, proliferation and migration of RA-FLSs via targeting nuclear factor of activated T cells 5 (38). In addition, miR-20a regulates the secretion of IL-6, IL-1β and TNF-α in FLSs via targeting apoptosis signal-regulating kinase 1 (39).…”

Section: Discussionmentioning

confidence: 99%

microRNA‑23 inhibits inflammation to alleviate rheumatoid arthritis via regulating CXCL12

et al. 2021

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Rheumatoid arthritis (RA) is a common systemic, inflammatory and autoimmune disorder. MicroRNAs (miRs) are strongly associated with the initiation and progression of RA. However, the functions and mechanisms underlying miR-23 in RA are not completely understood. Therefore, the present study aimed to investigate the molecular mechanisms underlying miR-23 in RA. A bioinformatics tool (StarBase) and a wide range of experimental assays, including reverse transcription-quantitative PCR, western blotting, luciferase reporter assays and ELISAs, were performed to investigate the biological role of miR-23 in RA. The results indicated that miR-23 was downregulated and chemokine C-X-C motif ligand 12 (CXCL12) was upregulated in RA samples compared with healthy samples. Furthermore, miR-23 overexpression suppressed inflammation via reducing TNF-α, IL-1β and IL-8 expression levels compared with the NC mimic group. Regarding the underlying mechanism, compared with NC mimic, miR-23 mimic decreased CXCL12 mRNA expression by binding to its 3'-untranslated region. Additionally, CXCL12 overexpression reversed miR-23 mimic-mediated effects on inflammation. NF-κB signaling is associated with inflammation. Therefore, the present study indicated that CXCL12 promoted inflammation by activating NF-κB signaling. In conclusion, miR-23 inhibited inflammation to alleviate RA by regulating CXCL12 via the NF-κB signaling pathway, which may serve as a potential target for the diagnosis and treatment of RA.

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“…Through an initial bioinformatics analysis and further confirmation with additional samples, we discovered that miR-338-5p was upregulated in serofast status patients compared with secondary syphilis and healthy control subjects. This miRNA was reported to be involved in many important biological processes: miR-338-5p can regulate the viability, proliferation, apoptosis, and migration of rheumatoid arthritis fibroblast-like synoviocytes by targeting NFAT5; miR-338-5p promotes glioma cell invasion by regulating TSHZ3 and MMP2; miR-338-5p modulates B-cell biological functions by targeting NF-κB1; miR-338-5p is closely correlated with the procedure of renal allograft antibody-mediated rejection [44][45][46][47]; and miR-338-5p can also indirectly regulate the BAFF signaling pathway by targeting immune cell cytokines such as TRAF3, participating in the immune response after renal transplantation and effecting the long-term survival of a transplanted kidney. These results indicate that miR-338-5p might be related to immunologic functions.…”

Section: Discussionmentioning

confidence: 99%