miR-26a-5p Regulates Synovial Fibroblast Invasion in Patients with Rheumatoid Arthritis by Targeting Smad 1

Zhang, Wei; Chen, Le; Jiang, Yi; Shen, Yongchun

doi:10.12659/msm.907816

Cited by 9 publications

(6 citation statements)

References 23 publications

(19 reference statements)

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“…MiRNAs are attached to non-coding RNA and responsible to cellular and physiological processes by targeting protein-coding genes at post-transcriptional levels [18, 19]. MiR-26a-5p, locating on the human chromosome 3p22 [20], was the targeted downstream gene which predicted by target scan and functions in the development, differentiation, and cycle regulation for many cancers. For example, Xu et al demonstrated that miR-26a-5p potentiated lung cancer cell metastasis via JAK2/STAT3 pathway by targeting ITGb8 [19].…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0051079 functions as an oncogene by regulating miR-26a-5p/TGF-β1 in osteosarcoma

2019

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BackgroundOsteosarcoma is a most common bone malignant tumor which threatens children and adolescents. Circular RNAs (circRNAs) fundamentally play essential roles in the progress and development of human cancers by sponging with microRNAs (miRNAs). However, the role of circRNAs in osteosarcoma is not clear. The aim of the study was to investigate the roles and molecular mechanism of circRNAs in osteosarcoma.ResultsThe data from qRT-PCR showed that circ_0051079 expression was higher in osteosarcoma cells and tissues compared to their normal controls. Meanwhile, bioinformatic analysis indicated that circ_0051079 was a sponge of miR-26a-5p, which was verified by luciferase activity assay. Subsequently, TGF-β1 was verified as a putative target mRNA of miR-26a-5p by luciferase assay. Cellular function assays were conducted and the findings revealed that circ_0051079/miR-26a-5p/TGF-β1 regulated osteosarcoma proliferation and metastasis.ConclusionThe study demonstrated that circ_0051079 could act as an oncogene via regulating miR-26a-5p/TGF-β1 and a potential biomarker for osteosarcoma diagnose.

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Section: Discussionmentioning

confidence: 99%

Hsa_circ_0051079 functions as an oncogene by regulating miR-26a-5p/TGF-β1 in osteosarcoma

2019

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“…Synovial tissue is an important part of the knee joint, which mostly includes synovial macrophages and fibroblast-like synoviocytes (FLS) (95); synoviocyte proliferation, invasion, and migration are essential for the RA pathology (96). Among synovial and FLS miRNAs, miR-21 (39), miR-26a-5p (41), miR-126 (50), miR-135a (51), miR-138 (54), miR-143 (56), miR-145 (56), miR-155 (58), and miR-421 (63) are overexpressed, whereas miR-19a (37), miR-20a (38), miR-22 (40), miR-27a (42), miR-29a (44), miR-34a (45), miR-137 (53), miR-140-3p (55), miR−152 (57), and miR-495 (68) are downregulated. The disturbed miRNAs enhance the expression level of proinflammatory cytokine (IL-6, IL-8, TNF-a, and IL-1b) and enzymes that erode the bone matrix (MMP-1 and MMP-3) by affecting Wnt (97,98), NF-kB (81,99), JAK/STAT (48,100), and TLR (101,102) pathways.…”

Section: Introductionmentioning

confidence: 99%

Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis

2022

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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that affect synovitis, bone, cartilage, and joint. RA leads to bone and cartilage damage and extra-articular disorders. However, the pathogenesis of RA is still unclear, and the lack of effective early diagnosis and treatment causes severe disability, and ultimately, early death. Accumulating evidence revealed that the regulatory network that includes long non-coding RNAs (lncRNAs)/circular RNAs (circRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNA) plays important roles in regulating the pathological and physiological processes in RA. lncRNAs/circRNAs act as the miRNA sponge and competitively bind to miRNA to regulate the expression mRNA in synovial tissue, FLS, and PBMC, participate in the regulation of proliferation, apoptosis, invasion, and inflammatory response. Thereby providing new strategies for its diagnosis and treatment. In this review, we comprehensively summarized the regulatory mechanisms of lncRNA/circRNA-miRNA-mRNA network and the potential roles of non-coding RNAs as biomarkers and therapeutic targets for the diagnosis and treatment of RA.

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“…Pannus formation is an important characteristic of RA, which is characterized by angiogenic factor-mediated angiogenesis and abnormal hyperplasia of the synovium (23). The pannus, which is composed mostly of FLS, is formed alongside a marked infiltration of lymphocytes and macrophages (24).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑34a‑3p inhibits proliferation of rheumatoid arthritis fibroblast‑like synoviocytes

2019

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Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial inflammation. Fibroblast-like synoviocytes (FLS) serve a vital role in the initiation and perpetuation of the immune response in patients with RA. The present study aimed to investigate the potential role of microRNA (miR)-34a-3p in the pathogenesis of RA. FLS were collected from patients with RA and osteoarthritis (OA). The miR-34a-3p mimics and inhibitor vectors were constructed and transfected into RAFLS using Lipofectamine ® 2000. Cell proliferation was determined by Cell Counting kit-8 assay and cell cycle progression was analyzed by flow cytometry. In addition, the expression levels of cell cycle control genes, matrix metalloproteinase (MMP)-1 and MMP-9, and pro-inflammatory cytokines were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The potential targets of miR-34a-3p were predicted by TargetScan and MiRWalk; the target genes were further verified using a luciferase reporter assay. The expression levels of miR-34a-3p were generally lower in RAFLS compared with in OAFLS. miR-34a-3p overexpression significantly inhibited the proliferation of FLS (P<0.01) by suppressing the expression levels of cyclin-dependent kinase 2, cell division cycle 25A and cyclin D1 (P<0.01), and arresting FLS cell cycle progression at the G 1 phase. Furthermore, the expression levels of MMP-1 and 9 were markedly decreased, as were the mRNA and protein expression levels of pro-inflammatory cytokines (tumor necrosis factor α and interleukin 6; P<0.01). Murine double minute 4 (MDM4) was predicted and verified as a potential target gene of miR-34a-3p; the 547–554 nt position of the MDM4 3′-untranslated region harbored one potential binding site for miR-204-3p. The results of the present study indicated that miR-34a-3p may be considered a promising therapeutic target for RA through inhibiting FLS proliferation and suppressing the production of pro-inflammatory cytokines and MMPs.

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miR-26a-5p Regulates Synovial Fibroblast Invasion in Patients with Rheumatoid Arthritis by Targeting Smad 1

Cited by 9 publications

References 23 publications

Hsa_circ_0051079 functions as an oncogene by regulating miR-26a-5p/TGF-β1 in osteosarcoma

Hsa_circ_0051079 functions as an oncogene by regulating miR-26a-5p/TGF-β1 in osteosarcoma

Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis

MicroRNA‑34a‑3p inhibits proliferation of rheumatoid arthritis fibroblast‑like synoviocytes

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