microRNA-126 targeting PIK3R2 promotes rheumatoid arthritis synovial fibro-blasts proliferation and resistance to apoptosis by regulating PI3K/AKT pathway

Gao, Jie; Zhou, Xiaoli; Kong, Ruina; Ji, Lianmei; He, Lingling; Zhao, Dongbao

doi:10.1016/j.yexmp.2015.12.015

Cited by 61 publications

(52 citation statements)

References 29 publications

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“…PIK3R2 is a key protein in the PI3K/Akt signaling pathway, and miR-126 plays various roles through regulation of the PIK3R2/PI3K/Akt pathway 25,26. As previously described, PI3K/Akt pathway activation occurs in bladder urothelial carcinomas, and the role of the PI3K/Akt/mTOR pathway in bladder cancer oncogenesis has been elucidated 21,27.…”

Section: Discussionmentioning

confidence: 87%

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

Xiao

Lin²,

Zhu

et al. 2016

OTT

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ObjectiveTo assess whether microRNA-126 (miR-126) targets phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2) and to determine the potential roles of miR-126 in regulating proliferation and invasion via the PIK3R2-mediated phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) signaling pathway in the human bladder BLS cell line.Materials and methodsA recombinant lentivirus (Lv) vector expressing miR-216 (Lv-miR-126) was successfully constructed, and Lv-miR-126 and Lv vector were transfected into the BLS cell line. A direct regulatory relationship between miR-126 and the PIK3R2 gene was demonstrated by luciferase reporter assays. To determine whether PIK3R2 directly participates in the miR-126-induced effects in BLS cells, anti-miR-126 and a PIK3R2 small interfering RNA (siRNA) were transfected into the BLS cells. Quantitative real-time polymerase chain reaction was used to measure miR-126 and PIK3R2 expressions. 5-Ethynyl-2′-deoxyuridine and colony formation assays to assess cell proliferation, flow cytometry for cell apoptosis and cell cycle analysis, Transwell assays for cell migration and invasion, and Western blots for PIK3R2, PI3K, phosphorylated PI3K (p-PI3K), Akt, and phosphorylated Akt (p-Akt) protein expressions were performed.ResultsLv-miR-126 significantly enhanced the relative expression of miR-126 in the BLS cells after infection (P<0.0001). MiR-126 overexpression inhibited the proliferation, cloning, migration, and invasion of BLS cells, promoted cell apoptosis, and induced S phase arrest (all P<0.05). PIK3R2, p-PI3K, and p-Akt protein expressions were significantly decreased in the BLS cells infected with Lv-miR-126. Luciferase assays showed that miR-126 significantly inhibited the PIK3R2 3′ untranslated region (3′UTR) luciferase reporter activity (P<0.05). The anti-miR-126 + PIK3R2 siRNA group had significantly decreased PIK3R2, p-PI3K, and p-Akt expressions compared with those of anti-miR-126 alone, as well as significantly decreased proliferation, invasion, and metastasis and increased apoptosis compared with the anti-miR-126 group (all P<0.05). Additionally, proliferation, invasion, and metastasis were significantly increased, and cell apoptosis was decreased compared with the PIK3R2 siRNA group (all P<0.05).ConclusionOverexpression of miR-126 negatively regulated the target gene PIK3R2 and further inhibited the PI3K/Akt signaling pathway, thereby inhibiting proliferation, migration, and invasion and promoting apoptosis in BLS cells.

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Section: Discussionmentioning

confidence: 87%

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

Xiao

Lin²,

Zhu

et al. 2016

OTT

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“…Interestingly, increasing angiogenesis together with renal blood flow have been recently observed in IRI rats treated with adipose mesenchymal stem cell exosomes and associated with the reversion of the kidney damage [54]. The catalytic subunit PI3-Kinase p85-beta, detected among the 50 major expressed proteins of CF proteome, has been recently correlated with cell cycle re-entry and proliferation via PI3K/Akt signaling pathway activation [55]. …”

Section: Discussionmentioning

confidence: 99%

Exosome and Microvesicle-Enriched Fractions Isolated from Mesenchymal Stem Cells by Gradient Separation Showed Different Molecular Signatures and Functions on Renal Tubular Epithelial Cells

Collino

Pomatto²,

Bruno

et al. 2017

Stem Cell Rev and Rep

139

119

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Several studies have suggested that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) may mediate MSC paracrine action on kidney regeneration. This activity has been, at least in part, ascribed to the transfer of proteins/transcription factors and different RNA species. Information on the RNA/protein content of different MSC EV subpopulations and the correlation with their biological activity is currently incomplete. The aim of this study was to evaluate the molecular composition and the functional properties on renal target cells of MSC EV sub-populations separated by gradient floatation. The results demonstrated heterogeneity in quantity and composition of MSC EVs. Two peaks of diameter were observed (90–110 and 170–190 nm). The distribution of exosomal markers and miRNAs evaluated in the twelve gradient fractions showed an enrichment in fractions with a flotation density of 1.08–1.14 g/mL. Based on this observation, we evaluated the biological activity on renal cell proliferation and apoptosis resistance of low (CF1), medium (CF2) and high (CF3) floatation density fractions. EVs derived from all fractions, were internalized by renal cells, CF1 and CF2 but not CF3 fraction stimulated significant cell proliferation. CF2 also inhibited apoptosis on renal tubular cells submitted to ischemia-reperfusion injury. Comparative miRNomic and proteomic profiles reveal a cluster of miRNAs and proteins common to all three fractions and an enrichment of selected molecules related to renal regeneration in CF2 fraction. In conclusion, the CF2 fraction enriched in exosomal markers was the most active on renal tubular cell proliferation and protection from apoptosis.Electronic supplementary materialThe online version of this article (doi:10.1007/s12015-016-9713-1) contains supplementary material, which is available to authorized users.

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“…PI3K/Akt signaling pathway was implicated in the progression of RA and plays important roles in regulating inflammation, proliferation, and migration of RA‐FLSs. This pathway was highly expressed in the synovial tissues of RA patients . Additionally, PI3K/Akt performs an important role in signal activation of NF‐κB.…”

Section: Discussionmentioning

confidence: 99%

“…This pathway was highly expressed in the synovial tissues of RA patients. [25][26][27] Additionally, PI3K/ Akt performs an important role in signal activation of NF-κB. NF-κB plays a vital role in inflammatory and immune responses.…”

Section: Discussionmentioning

confidence: 99%

Betulinic acid inhibits cell proliferation, migration, and inflammatory response in rheumatoid arthritis fibroblast‐like synoviocytes

Wang

Zhao

2018

J of Cellular Biochemistry

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Betulinic acid (BA), a pentacyclic triterpene derived from the bark of the white birch tree, has been reported to have a variety of pharmacological effects, including antioxidant, anti‐inflammatory, antitumor, immunomodulatory, and antiarthritis properties. However, the role of BA in rheumatoid arthritis (RA) remains unclear. Thus, the objective of this study was to examine the effects of BA on RA fibroblast‐like synoviocytes (RA‐FLS) proliferation, migration, and inflammatory response, and further explore the potential underlying mechanisms. Our results showed that BA inhibited the proliferation, migration, and invasion of RA‐FLSs. BA also attenuated tumor necrosis factor‐α (TNF‐α), enhanced matrix metalloproteinases (MMPs) expression, and inflammatory cytokines production in RA‐FLS. Furthermore, BA prevented the activation of Akt/NF‐κB pathway in RA‐FLS exposed to TNF‐α. In conclusion, these findings indicated that BA inhibits cell proliferation, migration, and inflammatory response in RA‐FLS; and the Akt/NF‐κB signaling pathway was involved in the protective effect of BA on RA‐FLS. Thus, BA might be a potential therapeutic agent for the treatment of RA.

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microRNA-126 targeting PIK3R2 promotes rheumatoid arthritis synovial fibro-blasts proliferation and resistance to apoptosis by regulating PI3K/AKT pathway

Cited by 61 publications

References 29 publications

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

Exosome and Microvesicle-Enriched Fractions Isolated from Mesenchymal Stem Cells by Gradient Separation Showed Different Molecular Signatures and Functions on Renal Tubular Epithelial Cells

Betulinic acid inhibits cell proliferation, migration, and inflammatory response in rheumatoid arthritis fibroblast‐like synoviocytes

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