Long noncoding RNA ZFAS1 suppresses chondrocytes apoptosis via miR-302d-3p/SMAD2 in osteoarthritis

Li, Jian; Liu, Mingting; Li, Xianrang; Shi, Hui; Sun, Shui

doi:10.1093/bbb/zbab008

Cited by 5 publications

(8 citation statements)

References 44 publications

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“…Li et al . found ZFAS1 sponged miR-302d-3p to regulate SMAD2 expression in OA [ 20 ]. In this study, we identified miR-7-5p as a downstream target of ZFAS1, which was also reported by Peng et al .…”

Section: Discussionmentioning

confidence: 99%

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LncRNA ZFAS1 protects chondrocytes from IL-1β-induced apoptosis and extracellular matrix degradation via regulating miR-7-5p/FLRT2 axis

et al. 2023

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Background Increasing evidence suggested that long non-coding RNAs (lncRNAs) played vital roles in osteoarthritis (OA) progression. In this study, we aimed to reveal the protective roles of lncRNA ZFAS1 in osteoarthritis (OA) and further investigated its underlying mechanism. Methods The chondrocytes were stimulated by IL-1β to establish an in vitro OA model. Then, the expression of ZFAS1, miR-7-5p, and FLRT2 in chondrocytes was determined by qRT-PCR. Gain- and loss-of-function assays of ZFAS1, miR-7-5p and FLRT2 were conducted. CCK-8 assay and flow cytometry analysis were performed to detect cell viability and apoptosis rate. The expression levels of cartilage-related proteins, including MMP13, ADAMTS5, Collagen II, and Aggrecan, were measured by western blot analysis. The interaction between ZFAS1 and miR-7-5p, as well as miR-7-5p and FLRT2, was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results The expression of ZFAS1 and FLRT2 was down-regulated, while the expression of miR-7-5p was up-regulated in chondrocytes exposed to IL-1β. ZFAS1 overexpression promoted cell viability and suppressed apoptosis in IL-1β-treated chondrocytes. Besides, ZFAS1 overexpression suppressed the expression of MMP13 and ADAMTS5, but promoted the expression of Collagen II and Aggrecan to suppress ECM degradation. The mechanistic study showed that ZFAS1 sponged miR-7-5p to regulate FLRT2 expression. Furthermore, the overexpression of miR-7-5p could neutralize the effect of ZFAS1 in IL-1β-treated chondrocytes, and suppression of FLRT2 counteracted the miR-7-5p down-regulation role in IL-1β-treated chondrocytes. Conclusions ZFAS1 could promote cell viability of IL-1β-treated chondrocytes via regulating miR-7-5p/FLRT2 axis. Trial registration Not applicable.

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Section: Discussionmentioning

confidence: 99%

“…In OA, Li et al . reported that ZFAS1 suppresses chondrocytes apoptosis through regulating miR-302d-3p/SMAD2 [ 20 ]. Nevertheless, the role and mechanism of ZFAS1 in OA remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

LncRNA ZFAS1 protects chondrocytes from IL-1β-induced apoptosis and extracellular matrix degradation via regulating miR-7-5p/FLRT2 axis

et al. 2023

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“…Li et al also found that ZFAS1 expression was lower, proliferation was expedited, and apoptosis was repressed in chondrocytes. These effects were found to be mediated by regulation of the miR-302d-3p-SMAD2 axis [ 15 ]. Both studies did not use LPS to stimulate the generation of the OA cell model; therefore, other properties of OA, including oxidative stress and inflammation, were not investigated.…”

Section: Discussionmentioning

confidence: 99%

“…However, other studies have revealed an oncogenic role of ZFAS1 in cancer progression [ 12–14 ]. Apart from its role in neoplasia pathogenesis, ZFAS1 participates in molecular cascades resulting in a series of disorders, such as OA [ 10 , 15 ], epilepsy [ 16 ], rheumatoid arthritis [ 17 , 18 ], and atherosclerosis [ 19 ]. MicroRNAs (miRs) are conservative small RNAs consisting of 20–22 nucleotides, capable of regulating gene expression in a post-transcriptional manner by combining with mRNA 3’-UTR, which then leads to mRNA degradation and translation suppression [ 20–22 ].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA ZNFX1 antisense 1 (ZFAS1) suppresses anti-oxidative stress in chondrocytes during osteoarthritis by sponging microRNA-1323

Wang

2022

Bioengineered

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LncRNAs play a regulatory role in osteoarthritis (OA); however, the detailed mechanism remains to be elucidated. This study aimed to investigate the role of lncRNA zinc finger NFX1-type containing 1 (ZNFX1) antisense 1 (ZFAS1) in OA progression and explore its possible mechanismsagainst oxidative stress. Human cartilage specimens were obtained from 10 patients without OA who underwent traumatic amputation and 25 patients with OA who underwent total knee replacement surgery. Chondrocytes were prepared from harvested articular cartilage. ZFAS1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) expression levels were analyzed using quantitative reverse transcription PCR and WB. The chondrocyte growth was indicated by MTT and colony formation assays. Chondrocyte apoptosis, reactive oxygen species generation, and anti-oxidative enzymes activities were also measured. ZFAS1 expression was reduced in OA samples and lipopolysaccharide (LPS)-treated chondrocytes used as an OA cell model mimic. ZFAS1 overexpression facilitated proliferation and repressed oxidative stress, inflammation, and apoptosis in LPS-induced chondrocytes. ZFAS1 also activated the anti-oxidative Nrf2-HO-1 pathway. ZFAS1 directly targeted miR-1323, which partially reversed the effects of ZFAS1 on chondrocyte proliferation, oxidative stress, inflammation, and apoptosis. Furthermore, Nrf2 was negatively regulated by miR-1323. The effect of miR-1323 inhibition was partly abrogated by the administration of brusatol, an Nrf2 inhibitor. Collectively, the results showed that ZFAS1 promoted chondrocyte proliferation and repressed oxidative stress, possibly by regulating the novel miR-1323-Nrf2 axis of the inflammation and apoptosis triggered by LPS, indicating that ZFAS1 is a promising therapeutic target for OA.

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“…Zinc finger NFX1-type containing 1 antisense RNA 1 (ZFAS1) is a lncRNA that inhibits apoptosis. Li et al [ 85 ] found low levels of expression of ZFAS1 in OA tissues, and further analysis showed that ZFAS1 accelerated the proliferation and inhibited the apoptosis of chondrocytes by regulating the miR-302d-3p/SMAD2 axis. Similarly, another group [ 86 ] reported that OACs had a lower level of expression of ZFAS1 than normal chondrocytes, and overexpression of ZFAS1 enhanced the viability, proliferative capacity, and migratory capacity of OACs whilst inhibiting the apoptosis and ECM synthesis of chondrocytes by targeting the Wnt3a signaling pathway.…”

Section: Regulatory Roles Of Lncrnas In Osteoarthritis Cartilagementioning

confidence: 99%

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

Zhang

et al. 2023

Biomolecules

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Osteoarthritis (OA) is the most common degenerative bone and joint disease that can lead to disability and severely affect the quality of life of patients. However, its etiology and pathogenesis remain unclear. It is currently believed that articular cartilage lesions are an important marker of the onset and development of osteoarthritis. Long noncoding RNAs (lncRNAs) are a class of multifunctional regulatory RNAs that are involved in various physiological functions. There are many differentially expressed lncRNAs between osteoarthritic and normal cartilage tissues that play multiple roles in the pathogenesis of OA. Here, we reviewed lncRNAs that have been reported to play regulatory roles in the pathological changes associated with osteoarthritic cartilage and their potential as biomarkers and a therapeutic target in OA to further elucidate the pathogenesis of OA and provide insights for the diagnosis and treatment of OA.

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Long noncoding RNA ZFAS1 suppresses chondrocytes apoptosis via miR-302d-3p/SMAD2 in osteoarthritis

Cited by 5 publications

References 44 publications

LncRNA ZFAS1 protects chondrocytes from IL-1β-induced apoptosis and extracellular matrix degradation via regulating miR-7-5p/FLRT2 axis

LncRNA ZFAS1 protects chondrocytes from IL-1β-induced apoptosis and extracellular matrix degradation via regulating miR-7-5p/FLRT2 axis

Long non-coding RNA ZNFX1 antisense 1 (ZFAS1) suppresses anti-oxidative stress in chondrocytes during osteoarthritis by sponging microRNA-1323

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

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