BMC GASTROENTEROLOGY
·
2023
·Vol. 23
·期 1
·1-10
·
IF 2.4
Xiang Ping,Ge Tingrui,Zhou Jingyi,Zhang Yonggang
Background Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues. Methods Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1 , miR-142-5p, and nuclear receptor coactivator-3 ( NCOA3 ) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1β, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits. Results CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1 . Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1 -plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si- NCOA3 . Conclusion CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.
研究领域:
分子生物学
·
胃肠病学
·
免疫学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2020
·
IF 3.383
Haifeng Zhang,Yajun Lian,Nanchang Xie,Xuan Cheng,Chen Chen,Hongliang Xu,Yake Zheng
MicroRNAs (miRNAs) are reported to involve in pathogenesis of temporal lobe epilepsy (TLE). miR-142–5p is found increased in TLE, but its role remains unknown. In the study, we established a mouse model of status epilepticus (SE) with pilocarpine and a cell model of TLE. Quantitative real-time PCR revealed an up-regulation of miR-142–5p and down-regulation of mitochondrial Rho 1 (Miro1) in the mouse mode of SE. Administration of miR-142–5p antagomirs via intracerebroventricular injection attenuated pilocarpine-induced SE and hippocampal damage, and alleviated mitochondrial dysfunction along with increased mitochondrial membrane potential and intracellular ATP and Ca (2+) levels. The expression of mitochondrial trafficking kinesin protein (Trak) 1 and Trak2 was up-regulated by inhibiting miR-142–5p. Antagomirs targeting miR-142–5p suppressed pilocarpine-induced oxidative stress as evidenced by decreased ROS generation and MPO activity, and increased SOD activity. Silencing miR-142–5p reduced neuronal death in pilocarpine-treated hippocampus and magnesium-free (MGF)-treated neurons. Inhibition of miR-142–5p decreased cytoplasmic Cytochrome C and increased mitochondrial Cytochrome C, reduced cleaved-caspase3 and Bax levels, and elevated Bcl2 in vivo and in vitro . Further, dual-luciferase assay verified Miro1 as a target of miR-142–5p, suggesting that miR-142–5p might function via targeting Mrio1. Depletion of Miro1 inhibited the protective effect of silencing miR-142–5p on hippocampal neurons in vitro . Taken together, down-regulation of miR-142–5p via targeting Miro1 inhibits neuronal death and mitochondrial dysfunction, and thus attenuates pilocarpine-induced SE, suggesting the potential involvement of miR-142–5p in the pathogenesis of TLE.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2022
·Vol. 52
·期 1
·48-59
·
IF 1.18
Guomin Lv,Yan Chen,Zhengyue Cheng,Lixiang Lin,Huasong Shen
Objective Osteoporosis is likely becoming a new disease challenge with increasing aging population. Circ_0006873 dysregulation mayserve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 onosteoporosis. Methods Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expressiondata. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools(starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression,cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP)staining detected osteoblastic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expressionof RNAs and proteins after transfection or during osteoblastic differentiation. Results circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experimentsrevealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblasticdifferentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 spongedmiR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescueassay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenicmarkers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTENto inhibit osteoblastic differentiation. Conclusion Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulationof Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochemistry Research International
·
2020
·
IF 0
Yaoyv Xiang,Yanlin Li,Lingjian Yang,Yinghong He,Di Jia,Xidan Hu
Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.
研究领域:
分子生物学
·
风湿病学
·
骨科学
✓ 已验证
DOI
PubMed
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