Dataset Information

Circular RNA circPDE4D Protects against Osteoarthritis by Binding to miR-103a-3p and Regulating FGF18.

ABSTRACT: Osteoarthritis (OA) is a common, age-related, and painful disease characterized by cartilage destruction, osteophyte formation, and synovial hyperplasia. This study revealed that circPDE4D, a circular RNA derived from human linear PDE4D, plays a critical role in maintaining the extracellular cellular matrix (ECM) during OA progression. circPDE4D was significantly downregulated in OA cartilage tissues and during stimulation with inflammatory cytokines. The knockdown of circPDE4D predominantly contributed to Aggrecan loss and the upregulation of matrix catabolic enzymes, including MMP3, MMP13, ADAMTS4, and ADAMTS5, but not proliferation or apoptosis. In a murine model of destabilization of the medial meniscus (DMM), the intraarticular injection of circPDE4D alleviated DMM-induced cartilage impairments. Mechanistically, we found that circPDE4D exerted its effect by acting as a sponge for miR-103a-3p and thereby regulated FGF18 expression, which is a direct target of miR-103a-3p. In conclusion, our findings highlight a novel protective role of circPDE4D in OA pathogenesis and indicate that the targeting of the circPDE4D-miR-103a-3p-FGF18 axis might provide a potential and promising approach for OA therapy.

SUBMITTER: Wu Y

PROVIDER: S-EPMC7791010 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circular RNA circPDE4D Protects against Osteoarthritis by Binding to miR-103a-3p and Regulating FGF18.

Wu Yizheng Y Hong Zhenghua Z Xu Wenbin W Chen Junxin J Wang Qingxin Q Chen Jiaxin J Ni Weiyu W Mei Zixuan Z Xie Ziang Z Ma Yan Y Wang Jiying J Lu Jianhong J Chen Chao C Fan Shunwu S Shen Shuying S

Molecular therapy : the journal of the American Society of Gene Therapy 20200905 1

Osteoarthritis (OA) is a common, age-related, and painful disease characterized by cartilage destruction, osteophyte formation, and synovial hyperplasia. This study revealed that circPDE4D, a circular RNA derived from human linear PDE4D, plays a critical role in maintaining the extracellular cellular matrix (ECM) during OA progression. circPDE4D was significantly downregulated in OA cartilage tissues and during stimulation with inflammatory cytokines. The knockdown of circPDE4D predominantly con ...[more]

PMID: 33125858

Similar Datasets

Project description:Autophagy and apoptosis are associated with cardiovascular diseases. Emerging evidence shows that microRNAs (miRs) are critical in the development of pathological processes underlying cardiovascular diseases by regulating the induction of apoptosis and autophagy. The present study aimed to investigate the role of miR‑103a‑3p in cardiomyocyte injury through autophagy and apoptosis. H9c2 cells were cultured under hypoxia and reoxygenation (H/R) conditions and were used to mimic cells under ischemia. The transfection of cells with miR‑103a‑3p (mimics and inhibitors) was performed to examine its function in cardiomyocytes. The expression levels of miR‑103a‑3p were evaluated by reverse transcription‑quantitative polymerase chain reaction analysis. Cell viability was determined using an MTT assay, and the lactate dehydrogenase assay (LDH) was used to investigate cell injury. The expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein, Beclin‑1, autophagy‑related 5 (Atg5), cleaved caspase‑3 and cleaved caspase‑9 were detected using western blotting. Immunofluorescence assays were performed to detect the expression of LC3 as a marker of autophagy. The target gene of miR‑103a‑3p was identified using dual‑luciferase reporter assays. The results revealed that the expression levels of miR‑103a‑3p were significantly downregulated in cardiomyocytes under H/R conditions. Injury of the cardiomyocytes was evaluated under H/R conditions. Following transfection of the cells with miR‑103a‑3p inhibitors, cell injury was increased, as determined by LDH and MTT assays. The expression levels of apoptotic proteins were consistent with the results obtained in the LDH and cell viability assays. The induction of autophagy was increased in cells under H/R conditions and cells with miR‑103a‑3p inhibitor transfection, whereas the induction of autophagy was decreased in cells transfected with miR‑103a‑3p mimics. In addition, the data indicated that miR‑103a‑3p directly targeted Atg5, which regulated the induction of autophagy and apoptosis. Taken together, these findings indicate that, following the inhibition of miR‑103a‑3p, Atg5 promotes autophagy and apoptosis in cardiomyocytes by directly targeting Atg5. Therefore, miR‑103a‑3p can be considered a potential therapeutic target for myocardial ischemia.

Project description:BackgroundRNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs).MethodsThe expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR. The expressions of MOV10, ZIC4, Hsp90 and PI3K/Akt were detected by real-time PCR or western blot. The binding ability of circ-SHKBP1 and miR-544a / miR-379, ZIC4 and miR-544a / miR-379 were analyzed with Dual-Luciferase Reporter System or RIP experiment. The direct effects of ZIC4 on the Hsp90β promoter were analyzed by the ChIP experiment. The cell viability, migration and tube formation in vitro were detected by CCK-8, Transwell assay and Matrigel tube formation assay. The angiogenesis in vivo was evaluated by Matrigel plug assay. Student's t-test (two tailed) was used for comparisons between two groups. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by Bonferroni post-hoc analysis.ResultsThe expressions of RNA binding proteins MOV10, circ-DICER1, ZIC4, and Hsp90β were up-regulated in GECs, while miR103a-3p/miR-382-5p were down-regulated. MOV10 binding circ-DICER1 regulated the cell viability, migration, and tube formation of GECs. And the effects of both MOV10 and circ-DICER1 silencing were better than the effects of MOV10 or circ-DICER1 alone silencing. In addition, circ-DICER1 acts as a molecular sponge to adsorb miR-103a-3p / miR-382-5p and impair the negative regulation of miR-103a-3p / miR-382-5p on ZIC4 in GECs. Furthermore, ZIC4 up-regulates the expression of its downstream target Hsp90β, and Hsp90 promotes the cell viability, migration, and tube formation of GECs by activating PI3K/Akt signaling pathway.ConclusionsMOV10 / circ-DICER1 / miR-103a-3p (miR-382-5p) / ZIC4 pathway plays a vital role in regulating the angiogenesis of glioma. Our findings not only provides novel mechanisms for the angiogenesis of glioma, but also provide potential targets for anti-angiogenesis therapies of glioma.

Project description:Osteoarthritis (OA) is a widespread chronic bone and joint disease for which there is currently no effective preventive or therapeutic treatment. Accumulating evidence indicates that circular RNAs (circRNAs), a class of noncoding RNAs, play critical roles in OA. Therefore, in this study, we aimed to reveal an unexplored circTBCK and elucidate its mechanism of action in the pathological process of OA. The different expression of circTBCK was obtained both in vitro and in vivo. In the in vivo model, mice were induced via destabilization of the medial meniscus (DMM) surgery, while in vitro model, mouse cells like primary chondrocytes of newborn mice and ATDC5 cell line were treated with IL-1β treatment (10 ng/mL for 24 h). The level of circTBCK was examined by quantitative real-time polymerase chain reaction (qRT-PCR). After circTBCK was overexpressed or knocked down, IL-1β treatment was performed, and then, chondrocyte viability was detected via a Cell Counting Kit-8 (CCK-8) assay at 0, 24, 48, or 72 h. To assess type II collagen (Collagen II) expression, immunofluorescence (IF) analysis was used. The levels of mRNAs and proteins related to proliferation, the extracellular matrix (ECM) and autophagy were determined by qRT-PCR and Western blotting. Compared with OA treatment, primary chondrocytes with treatment of both circTBCK overexpression and IL-1βincreased the expression of anabolic factors-Collagen II and SRY-box transcription factor 9 (SOX9), proliferation-related molecules-Ki-67 and proliferating cell nuclear antigen (PCNA), and autophagy-related molecules-Microtubule-associated protein 1 light chain 3 (LC3), B-cell lymphoma 1 (Bcl1), and autophagy-related 5 (Atg5) and decreased Sequestosome 1 (SQSTM1 or P62). In contrast, knockdown of circTBCK aggravated the chondrocyte degeneration induced by IL-1β. Overall, our findings suggest that circTBCK, an unexplored circRNA, could regulate autophagy, proliferation, and the extracellular matrix (ECM) to mitigate the development of OA, suggesting a possible target for OA prevention and therapy.

Dataset Information

Circular RNA circPDE4D Protects against Osteoarthritis by Binding to miR-103a-3p and Regulating FGF18.

Publications

Circular RNA circPDE4D Protects against Osteoarthritis by Binding to miR-103a-3p and Regulating FGF18.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets