MicroRNA‑let‑7a inhibition inhibits LPS‑induced inflammatory injury of chondrocytes by targeting IL6R

Sui, Cong; Zhang, Lecheng; Hu, Yong

doi:10.3892/mmr.2019.10493

Cited by 21 publications

(18 citation statements)

References 47 publications

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“…In an experiment comparing miRNA expression in synovial fluid from human OA patients undergoing hyaluronic acid treatment, let-7a was significantly upregulated in synovial fluid of OA samples compared to healthy controls; levels of let-7a in affected patients returned to normal after hyaluronan injection [ 32 ]. Let-7a is thought to regulate IL-6 receptor (IL6R), and its inhibition can enhance cell proliferation, reduce apoptosis and inhibit inflammatory response in ATDC5 cells in a LPS-induced in vitro model of OA [ 44 ]. Members of the let-7 family have often been described in studies involving OA; a large population-based study identified serum let-7e as a promising candidate to predict OA risk, independent of age, sex and body mass index [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis

et al. 2021

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Background Osteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potentially provide early biomarkers. Methods Small RNA sequencing was performed using synovial fluid from the metacarpophalangeal joints of both control and early osteoarthritic horses. A group of differentially expressed sncRNAs was selected for further validation through qRT-PCR using an independent cohort of synovial fluid samples from control and early osteoarthritic horses. Bioinformatic analysis was performed in order to identify putative targets of the differentially expressed microRNAs and to explore potential associations with specific biological processes. Results Results revealed 22 differentially expressed sncRNAs including 13 microRNAs; miR-10a, miR-223, let7a, miR-99a, miR-23b, miR-378, miR-143 (and six novel microRNAs), four small nuclear RNAs; U2, U5, U11, U12, three small nucleolar RNAs; U13, snoR38, snord96, and one small cajal body-specific RNA; scarna3. Five sncRNAs were validated; miR-223 was significantly reduced in early osteoarthritis and miR-23b, let-7a-2, snord96A and snord13 were significantly upregulated. Significant cellular actions deduced by the differentially expressed microRNAs included apoptosis (P < 0.0003), necrosis (P < 0.0009), autophagy (P < 0.0007) and inflammation (P < 0.00001). A conservatively filtered list of 57 messenger RNA targets was obtained; the top biological processes associated were regulation of cell population proliferation (P < 0.000001), cellular response to chemical stimulus (P < 0.000001) and cell surface receptor signalling pathway (P < 0.000001). Conclusions Synovial fluid sncRNAs may be used as molecular biomarkers for early disease in equine osteoarthritic joints. The biological processes they regulate may play an important role in understanding early osteoarthritis pathogenesis. Characterising these dynamic molecular changes could provide novel insights on the process and mechanism of early osteoarthritis development and is critical for the development of new therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis

et al. 2021

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“…IL-6R is downregulated by upregulated miR-423-5p, let-7a-5p, let-7c-5p in the group of patients with NASH. Sui et al (2019) showed that IL-6R was identified as a direct target of let-7a ( Sui et al, 2019 ). The authors showed that the let-7a inhibitor significantly increased the level of IL-6R expression, resulting in increased proliferation of liver cells.…”

Section: Discussionmentioning

confidence: 99%

Analysis of miRNAs Profiles in Serum of Patients With Steatosis and Steatohepatitis

Vulf

Skuratovskaia

Komar

et al. 2021

Front. Cell Dev. Biol.

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Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases worldwide, affecting 25% of the world population. In recent years, there has been increasing evidence for the involvement of microRNAs in the epigenetic regulation of genes taking part in the development of steatosis and steatohepatitis—two main stages of NAFLD pathogenesis. In the present study, miRNA profiles were studied in groups of patients with steatosis and steatohepatitis to compare the characteristics of RNA-dependent epigenetic regulation of the stages of NAFLD development. According to the results of miRNA screening, 23 miRNAs were differentially expressed serum in a group of patients with steatohepatitis and 2 in a group of patients with steatosis. MiR-195-5p and miR-16-5p are common differentially expressed miRNAs for both steatosis and steatohepatitis. We analyzed the obtained results: the search for target genes for the differentially expressed miRNAs in our study and the subsequent gene set enrichment analysis performed on KEGG and REACTOME databases revealed which metabolic pathways undergo changes in RNA-dependent epigenetic regulation in steatosis and steatohepatitis. New findings within the framework of this study are the dysregulation of neurohumoral pathways in the pathogenesis of NAFLD as an object of changes in RNA-dependent epigenetic regulation. The miRNAs differentially expressed in our study were found to target 7% of genes in the classic pathogenesis of NAFLD in the group of patients with steatosis and 50% in the group of patients with steatohepatitis. The effects of these microRNAs on genes for the pathogenesis of NAFLD were analyzed in detail. MiR-374a-5p, miR-1-3p and miR-23a-3p do not target genes directly involved in the pathogenesis of NAFLD. The differentially expressed miRNAs found in this study target genes largely responsible for mitochondrial function. The role of miR-423-5p, miR-143-5p and miR-200c-3 in regulating apoptotic processes in the liver and hepatocarcinogenesis is of interest for future experimental studies. These miR-374a, miR-143, miR-1, miR-23a, and miR-423 have potential for steatohepatitis diagnosis and are poorly studied in the context of NAFLD. Thus, this work opens up prospects for further studies of microRNAs as diagnostic and therapeutic biomarkers for NAFLD.

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“…However, the present study only focused on the association between miR4435-2HG and NF-κB signaling pathway. Since IL-6/STAT3 are involved in the progression of OA ( 50 , 51 ), the effect of MIR4435-2HG on IL-6/STAT3 signaling should be investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

LncRNA MIR4435‑2HG inhibits the progression of osteoarthritis through miR‑510‑3p sponging

et al. 2020

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Osteoarthritis (OA) is a disorder of diarthrodial joints that can have multiple causes. Long non-coding RNAs (lncRNAs) participate in multiple diseases, including OA. It has recently been reported that the lncRNA microRNA 4435-2HG (MIR4435-2HG) is downregulated in OA tissues; however, the biological role of MIR4435-2HG during OA progression remains unclear. In the present study, interleukin (IL)-1β was used to establish an in vitro model of OA. Protein expressions of matrix metallopeptidase (MMP) 1, MMP13, collagen II, interleukin (IL)-17A, p65, phosphorylated (p)-p65, IκB and p-IκB in CHON-001 cells were detected by western blotting. Gene expressions of IL-17A, MIR4435-2HG and miR-510-3p in tissues or CHON-001 cells were measured by reverse transcription-quantitative PCR and western blotting, respectively. Cell Counting Kit-8 assay and immunofluorescence staining were used to investigate cell proliferation, and cell apoptosis was detected by flow cytometry. The association between MIR4435-2HG, miR-510-3p and IL-17A was investigated using the dual luciferase report assay. MIR4435-2HG and miR-510-3p overexpression were transfected into CHON-001 cells. The results demonstrated that miR4435-2HG overexpression significantly increased proliferation and inhibited apoptosis of CHON-001 cells. In addition, miR-510-3p was identified as the downstream target of MIR4435-2HG, and miR-510-3p directly targeted IL-17A. The results from the present study suggested that MIR4435-2HG could mediate the progression of OA by inactivating the NF-κB signaling pathway. In addition, miR4435-2HG overexpression inhibited OA progression, suggesting that miR4435-2HG may be considered as a potential therapeutic target in OA.

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MicroRNA‑let‑7a inhibition inhibits LPS‑induced inflammatory injury of chondrocytes by targeting IL6R

Cited by 21 publications

References 47 publications

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis

Analysis of miRNAs Profiles in Serum of Patients With Steatosis and Steatohepatitis

LncRNA MIR4435‑2HG inhibits the progression of osteoarthritis through miR‑510‑3p sponging

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