Experimental and Therapeutic Medicine
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2019
·Vol. 18
·期 2
·1285-1290
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IF 1.448
Hanchun Chen,Qiong Lu,Chao Chen,Yunhai Di,Ya'nan Li,Weijie Min,Zhengquan Yu,Dongwei Dai
Mutations of the β‑catenin gene are common in various cancer types. MicroRNA (miR)‑24 suppresses gene expression during the cell cycle. However, the effects of miR‑24 on the cell viability and autophagy of glioma cells, and how these biological processes are regulated by β‑catenin are largely unclear. The current study aimed to investigate the role of β‑catenin in regulating the effects of miR‑24 on the cell viability and autophagy of glioma cells. The expression levels of microtubule‑associated proteins 1A/1B light chain 3B (LC3B) and Beclin1 were detected by immunohistochemistry and western blotting. Glioma C6 cells were transfected with miR‑24 mimics, miR‑24 inhibitors and negative control miRNAs. C6 cells transfected with miR‑24 mimics or negative control miRNAs were treated with the β‑catenin inhibitor, XAV‑939. An MTT assay was utilized to evaluate the viability of C6 cells. The expression of miR‑24 and mRNA expression of autophagy related 4a cysteine peptidase (ATG4A) were detected by quantitative polymerase chain reaction analysis. The protein expression of LC3B and Beclin1 decreased significantly in glioma tissue and glioma C6 cells compared with normal brain tissue. Compared with the negative control group, C6 cells transfected with miR‑24 mimics exhibited significantly higher cell viability at 24 and 48 h, and those transfected with miR‑24 inhibitors exhibited significantly lower cell viability at 48 h. XAV‑939 decreased the stimulatory effects of miR‑24 mimics on the viability of C6 cells. The expression of miR‑24 significantly decreased and ATG4A mRNA significantly increased in C6 cells transfected with XAV‑939 compared with those transfected with the negative control miRNA. XAV‑939 attenuated the miR‑24‑induced decrease of the protein expression of LC3B and Beclin1, and decreased the stimulatory effects of miR‑24 mimics on cell viability. In addition, XAV‑939 attenuated the miR‑24‑induced decrease of autophagy marker expression by attenuating miR‑24 expression and increasing ATG4A mRNA expression in glioma C6 cells. To the best of our knowledge, the present study is the first to demonstrate whether β‑catenin regulates the intracellular effects of miR‑24 on the viability and autophagy of glioma cells. The results also provide some mechanistic basis to the pharmaceutical targeting of WNT signaling in high grade glial tumors.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2020
·Vol. 34
·期 3
·3583-3593
·
IF 4.966
Bu Yang,Shangfu Li,Zheng Chen,Feng Feng,Lei He,Bin Liu,Tianwei He,Xuan Wang,Ruiqiang Chen,Zihao Chen,Peigen Xie,Limin Rong
Background Amyloid β peptide (Aβ) is involved in osteoporosis, but the effects of Aβ on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aβ on bone formation. Methods An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aβ. The effect of Aβ on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. Results In the animal study, intraperitoneal injection of Aβ for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aβ treatment significantly elevated osterix + (osteoblastic) cells but decreased TRAP + cells (osteoclasts) in the distal femur bone. In vitro study showed that Aβ treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aβ treatment activated Wnt/β-catenin signaling in hBMSCs. The effect of Aβ was blocked by DKK1 (a Wnt/β-catenin inhibitor) treatment. In the co-culture system, Aβ treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP + RAW264.7 cells (pre-osteoclasts). Aβ treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aβ treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). Conclusion Aβ treatment simultaneously promoted osteogenic differentiation via Wnt/β-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aβ is a positive regulator of osteoblast differentiation and bone formation.
研究领域:
生物学
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医学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2025
·Vol. 33
·期 1
·1-10
·
IF 3.5
Hongwei Xiao,Jianfeng Li,Wei Huang,Yi Qin
Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.
研究领域:
分子医学
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遗传学
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病理学
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药理学
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DOI
PubMed
高影响因子
BIOSCIENCE REPORTS
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2019
·Vol. 39
·期 1
·
IF 2.535
Chen Gang,Chen Weicheng,Ye Ming,Tan Weiqiang,Jia Bing
Neuroblastoma is the most common tumor in children, with a very poor prognosis. It is urgent to identify novel biomarkers to treat neuroblastoma, together with surgery, chemotherapy, and radiation. Human tripartite motif 59 (TRIM59), a member of the TRIM family, has been reported to participate in several human tumors. However, the exact role of TRIM59 in neuroblastoma is unknown. In the present study, real-time PCR and Western blot were used to measure mRNA and protein levels of TRIM59 in four neuroblastoma cell lines and in neuroblastoma tissues. Lentiviruses targeting TRIM59 were used to up/down-regulate TRIM59 expression levels. Cell Counting Kit-8 and Annexin-V/PI were used to analyze cell proliferation and apoptosis in neuroblastoma cell lines. Our data showed that TRIM59 knockdown inhibits cell proliferation while inducing apoptosis in SH-SY5Y and SK-N-SH neuroblastoma cell lines. TRIM59 knockdown up-regulated expression of Bax and Bim and down-regulated levels of Survivin, β-catenin, and c-myc. Interestingly, the inhibition of cell proliferation caused by TRIM59 knockdown could be blocked by LiCl, which is an agonist of Wnt/β-catenin signaling pathway. In contrast, TRIM59 overexpression could increase cell proliferation, up-regulate Survivin, β-catenin and c-myc, down-regulate Bax and Bim, and these effects could be blocked by XAV939, which is an inhibitor of Wnt/β-catenin signaling pathway. In addition, TRIM59 was up-regulated and positively related with β-catenin in neuroblastoma tissues. In conclusion, TRIM59 was up-regulated in neuroblastoma, and TRIM59 knockdown inhibited cell proliferation by down-regulating the Wnt/β-catenin signaling pathway in neuroblastoma.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Yuan Xu,Jian He,Jun He
Purpose The treatment of intervertebral disc degeneration is limited, cyanidin can protect chondrocytes from degeneration. This research investigated the effect of cyanidin on human nucleus pulposus cells (HNPC) metabolism and its mechanism. Methods HNPC were treated with cyanidin, XAV-939 (inhibitor of Wnt/β-catenin signaling) and SKL2001 (activator of Wnt/β-catenin signaling), and pressurized at 1, 3, and 30 atm. Quantitative real-time PCR and Western blot were used to assess the expressions of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), Collagen-II, Aggrecan , Wnt-3a and β-catenin in treated HNPC. Cell counting kit-8 was used to detect the HNPC cell viability . Radioisotope incorporation method was used to assess the proteoglycan synthesis rate of HNPC. The level of cell matrix was detected by toluidine blue staining. Results Proper hydrostatic pressure of 3 atm could elevate cell viability, proteoglycan synthesis and the level of cell matrix of HNPC, while high hydrostatic pressure of 30 atm reduced the above effects. Cyanidin and XAV-939 reversed the promoting effect of 30 atm pressure on Wnt/β-catenin signaling pathway and the inhibiting effect on cell viability, proteoglycan synthesis and the level of cell matrix. Subsequently, SKL2001 further reversed the function of cyanidin on HNPC. Conclusion Cyanidin attenuated the high hydrostatic pressure-induced degradation of cellular matrix of HNPC via blocking the Wnt/β-catenin signaling pathway. Our findings in this research provided a basis for in vitro experiment of cyanidin and a theoretical fundament on this disease.
研究领域:
骨科
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Xin Wang,Shoulin Li,Cheng Zhang,Wenping Xu,Mengqi Wu,Jiagao Cheng,Zhong Li,Liming Tao,Yang Zhang
Acetochlor (ACT) is a widely detected pesticide globally, and the neurotoxic effects of its chiral isomers on humans and environmental organisms remain uncertain. Zebrafish were used to study the neurotoxicity of ACT and its chiral isomers. Our study reveals that the R -ACT, Rac -ACT, and S -ACT induce neurotoxicity in zebrafish larvae by impairing vascular development and disrupting the blood-brain barrier. These detrimental effects lead to apoptosis in brain cells, hindered development of the central nervous system, and manifest as altered swimming behavior and social interactions in the larvae. Importantly, the neurotoxicity caused by the S -ACT exhibits the most pronounced impact and significantly diverges from the effects induced by the R -ACT. The neurotoxicity associated with the Rac -ACT falls intermediate between that of the R -ACT and S -ACT. Fascinatingly, we observed a remarkable recovery in the S -ACT-induced abnormalities in BBB, neurodevelopment, and behavior in zebrafish larvae upon supplementation of the Wnt/β-catenin signaling pathway. This observation strongly suggests that the Wnt/β-catenin signaling pathway serves as a major target of S -ACT-induced neurotoxicity in zebrafish larvae. In conclusion, S -ACT significantly influences zebrafish larval neurodevelopment by inhibiting the Wnt/β-catenin signaling pathway, distinguishing it from R -ACT neurotoxic effects.
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PubMed
高影响因子
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