BIOSCIENCE REPORTS
·
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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DOI
PubMed
高影响因子
Cells
·
2025
·Vol. 14
·期 6
·394
·
IF 5.2
Min Jiang,Jiaqi Hou,Qianqian Chai,Shihao Yin,Qian Liu
Pulmonary fibrosis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of death in patients with COVID-19. β-catenin, a key molecule in the Wnt/β-catenin signaling pathway, has been shown to be involved in the development of pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis, silicosis). In this study, we developed a SARS-CoV-2-infected A549-hACE2 cell model to evaluate the efficacy of the A549-hACE2 monoclonal cell line against SARS-CoV-2 infection. The A549-hACE2 cells were then subjected to either knockdown or overexpression of the effector β-catenin, and the modified cells were subsequently infected with SARS-CoV-2. Additionally, we employed transcriptomics and raw letter analysis approaches to investigate other potential effects of β-catenin on SARS-CoV-2 infection. We successfully established a model of cellular fibrosis induced by SARS-CoV-2 infection in lung-derived cells. This model can be utilized to investigate the molecular biological mechanisms and cellular signaling pathways associated with virus-induced lung fibrosis. The results of our mechanistic studies indicate that β-catenin plays a significant role in lung fibrosis resulting from SARS-CoV-2 infection. Furthermore, the inhibition of β-catenin mitigated the accumulation of mesenchymal stroma in A549-hACE2 cells. Additionally, β-catenin knockdown was found to facilitate multi-pathway crosstalk following SARS-CoV-2 infection. The fact that β-catenin overexpression did not exacerbate cellular fibrosis may be attributed to the activation of PPP2R2B.
研究领域:
分子生物学
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病毒学
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医学
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DOI
PubMed
高影响因子
APOPTOSIS
·
2025
·
IF 8.1
Miao Jintian,Jiang Xinyan,Wang Siyun
Cisplatin resistance significantly hinders the efficacy of ovarian cancer treatment, presenting a major challenge in improving patient outcomes. This study identifies the m6A reader protein YTHDF1 as a key regulator of cisplatin resistance in ovarian cancer through its modulation of the FZD7/Wnt/β-catenin signaling pathway. Using cisplatin-resistant ovarian cancer cell lines (A2780/DDP and SKOV3/DDP), we observed elevated YTHDF1 expression, which positively correlated with tumor cell proliferation and migration. Silencing YTHDF1 reduced FZD7 expression, inhibited Wnt/β-catenin signaling, and restored cisplatin sensitivity both in vitro and in vivo. Mechanistic investigations revealed that YTHDF1 binds to m6A-modified FZD7 mRNA, enhancing its stability and translation. Functional studies in xenograft mouse models demonstrated that targeting YTHDF1 suppressed tumor growth and enhanced apoptosis in cisplatin-resistant ovarian cancer cells. These findings highlight the YTHDF1-FZD7 axis as a novel therapeutic target for overcoming cisplatin resistance, paving the way for improved treatment strategies in ovarian cancer.
研究领域:
肿瘤学
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 7
·e70539
·
IF 4.2
Tianyi Ji,Xiangying Li,Jiachen Li,Guan Wang
Wnt signalling is a highly conserved signalling pathway that plays an important role in a variety of biological processes. Frizzled (Fzd) family proteins are receptors for Wnt ligands. The physiological processes involved in mature trafficking of Fzd proteins remain elusive. Here, we identified asparagine residues 59 and 144 as the N-glycosylation modification sites of Fzd4. Sequence analysis of Fzd4 in different species showed that the two asparagine residues were highly conserved. N-glycosylation modification of Fzd4 is indispensable for its maturation and transport to the plasma membrane. N-glycosylation modification enhances the stability of Fzd4 and is also necessary for Fzd4 activity, which promotes Fzd4 interaction with Wnt ligands and co-receptor Norrin. Knockout of Fzd4 in the non-small cell lung cancer (NSCLC) cell line A549 followed by replenishment of Fzd4 glycosylation site mutants inhibited the growth and migration ability of A549 cells in vitro and in vivo. In summary, we identified N-glycosylation modification sites of Fzd4. N-glycosylation modification of Fzd4 is necessary for its stability and activity. When N-glycosylation modification is absent, Fzd4 cannot mediate the Wnt/β-catenin signalling pathway, which can inhibit the proliferation and migration of NSCLC and provide new targets and strategies for the treatment of NSCLC.
研究领域:
细胞生物学
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分子生物学
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肿瘤学
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DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2024
·
IF 3.3
Zhen Xu,Yilin Guo,Lu Wang,Jinquan Cui
HECW1 belongs to ubiquitin ligase (E3) HECT family, and is found to be involved in tumorigenesis and tumor progression. However, the function of HECW1 in cervical cancer (CC) remains unknown. Clinical analysis showed that HECW1 is significantly decreased in CC tumor tissues. Ectopic expression of HECW1 suppressed cell growth, promoting cell cycle arrest and apoptosis in CC cells, while downregulation of HECW1 reversed these trends, impeded proliferation and accelerated cell cycle progression of CC cells. Overexpressing of HECW1 reduced mitochondrial membrane potential and the protein expression of voltage-dependent anion channel 1 (VDAC1). In addition, upregulation of HECW1 inhibited nuclear β-catenin accumulation, downregulated β-catenin/TCF/LEF-mediated transcriptional activity and the expression of downstream gene c-Myc, whereas inhibition of HECW1 received opposite results. Further results confirmed HECW1 affects the protein expression of dishevelled-1 (DVL1), a potent activator of Wnt/β‐catenin, and inhibition of HECW1 inhibited the ubiquitination of DVL1, upregulating its expression. Inhibition of DVL1 restrained the promotion effect of HECW1 suppression on cell proliferation. In vivo experiments also verified that HECW1 suppression promoted the tumor formation of CC cells. Summary, we demonstrated that HECW1 inhibits CC cell proliferation and tumor formation by downregulating DVL1 induced Wnt/β‐catenin signaling pathway activation.
研究领域:
肿瘤学
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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
MOLECULAR CARCINOGENESIS
·
2024
·
IF 3
Junyi Jin,Yihui Wang,Yaoyuan Hu
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. STAM binding protein-like 1 (STAMBPL1), a key member of the COP9 signalosome subunit 5/serine protease 27/proteasome 26S subunit non-ATPase 7 (JAMM) family, is closely associated with tumor development. In this work, data from GSE101728 and GSE84402 chips were analyzed, and STAMBPL1 was selected as the target factor. This study aimed to reveal the potential function of STAMBPL1 in HCC. Clinical results showed that STAMBPL1 was significantly increased in tumor tissues of HCC patients, and its expression was strongly associated with tumor size and TNM stage. Furthermore, STAMBPL1-overexpressed Hep3B2.1-7 cell line or STAMBPL1-silenced SNU-182 cell line were established using lentivirus carrying cDNA encoding STAMBPL1 mRNA or shRNA targeting STAMBPL1, respectively. STAMBPL1-overexpressed cells exhibited a pronounced enhancement of proliferation in vitro and in vivo. Exogenous expression of STAMBPL1 increased the percentage of cells in the S phase and upregulated the expressions of CyclinD1 and Survivin. As expected, STAMBPL1 knockdown exhibited completely opposite effects, resulting in impaired tumorigenicity in vitro and in vivo. Mechanistically, STAMBPL1 activated Wnt/β-catenin pathway and increased the expression of downstream cancer-promoting genes. Interestingly, we found that STAMBPL1 was transcriptionally regulated by sterol regulatory element-binding protein 1 (SREBP1), a modulator of lipid metabolism, as evidenced by luciferase reporter and chromatin-immunoprecipitation (Ch-IP) assays. Notably, STAMBPL1 overexpression increased lipid accumulation in HCC cells and xenograft tumors. Totally our findings suggest that STAMBPL1 plays a vital role in the tumorigenicity of HCC cells. Modulation of Wnt/β-catenin and lipid metabolism may contribute to its pro-cancer effects. STAMBPL1 may serve as a therapeutic target of HCC.
研究领域:
肿瘤学
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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
Frontiers in Pharmacology
·
2025
·
IF 4.8
Zhize Liu,Weitao He,Jingwei Zhang,Bo Su,Jiang Mu,Xintao Wang
Introduction: Paederia scandens (Lour.) Merr. (P. scandens), a widely consumed edible wild botanical drug in East Asia, has traditionally been used in folk medicine for its purported health-promoting effects, including the relief of fractures, rheumatoid arthritis, and pain. Despite its common use, the bioactive metabolites and underlying mechanisms of action remain insufficiently understood. This study investigates the pharmacological effects and molecular mechanisms of P. scandens in the context of osteoporosis.Methods: An ovariectomized (OVX) rat model of osteoporosis was used to evaluate the effects of P. scandens extract on bone health. Network pharmacology analysis identified candidate metabolites related to osteoblast differentiation. Paederoside, the primary plasma-absorbed metabolite, was validated in OVX rats via HPLC-Q-TOF-MS. In vitro experiments assessed osteogenesis and osteoclast activity using an osteoblast-osteoclast co-culture system, while in vivo studies evaluated serum calcium and phosphorus levels, bone morphology, and bone mass.Results: P. scandens extract significantly improved bone mass, bone mineral density (BMD), and the trabecular bone microstructure in the OVX rat model. Paederoside promoted osteogenesis and suppressed osteoclast activity in vitro. In vivo, paederoside demonstrated pronounced anti-osteoporotic effects, as evidenced by elevated serum calcium and phosphorus levels, improved bone morphology, and increased bone mass. Paederoside upregulated osteogenesis-related markers (BMP2, Smad1, Col1a1, Bglap, Osterix, and Runx2) and downregulated osteoclastogenesis-related markers (RANKL, NFATc1, Acp5, Ctsk, and Mmp9). Transcriptomic analysis revealed that paederoside modulated the Wnt/β-catenin signaling pathway, inducing Wnt3a expression, inhibiting GSK-3β and β-catenin phosphorylation, and upregulating downstream targets such as Cyclin D1 and c-Myc.Discussion: In conclusion, P. scandens exerts protective effects against osteoporosis, and paederoside, identified as a primary plasma-absorbed metabolite, enhances osteoblastogenesis and suppresses osteoclastogenesis, likely through the upregulation of the Wnt/β-catenin signaling pathway. This study elucidates the health benefits of P. scandens and paederoside in the prevention and treatment of osteoporosis.
研究领域:
药理学
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分子生物学
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骨生物学
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天然产物化学
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药物代谢
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转化医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Hanxiao Zheng,Limin Qu,Lei Yang,Xianmin Xie,Ling Song,Qiuen Xie
Knee osteoarthritis (KOA) is a chronic disease characterized by joint wear and cartilage degeneration. Current clinical treatments are based on symptomatic relief and are not effective in regenerating cartilage, and inflammation-induced cartilage damage accelerates the progression of osteoarthritis, making the protection of articular cartilage important for controlling the development of knee osteoarthritis. In this study, a biodegradable hydrogel (HA-Ca-Alg@Ica) loaded with Icariin (Ica) was prepared by in situ cross-linking of hyaluronic acid-calcium complex (HA-Ca) and sodium alginate (Alg-Na) for local sustained delivery of Ica. The hydrogel promoted chondrocyte proliferation and inhibited the degradation of cartilage matrix by regulating key factors (Wnt3a, β-catenin and GSK-3β) in the Wnt/β-catenin signaling pathway. In addition, the hydrogel reduced the expression of inflammatory factors, including IL-1β, IL-6, TNF-α, COX-2, and MMP13, leading to a reduction in inflammation and pain relief. In summary, this hydrogel containing Icariin has shown significant effects in reducing chondrocyte degradation and promoting chondrocyte proliferation, which can play a role in delaying osteoarthritis by protecting chondrocytes. These findings offer innovative prospects for the therapeutic management of knee osteoarthritis.
研究领域:
生物材料学
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医学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·Vol. 479
·期 7
·1747-1766
·
IF 3.5
Wang Qun,Lu Weijun,Lu Li,Wu Ruopu,Wu Dongde
Receptor interacting protein serine/threonine kinase 4 (RIPK4) is widely involved in human cancer development. Nevertheless, its role in colon cancer (COAD) has not been elucidated till now. Our research aimed at exploring the function and underlying molecular mechanism of RIPK4 in COAD progression. Through bioinformatic analyses and RT-qPCR, RIPK4 was discovered to be increased in COAD cells and tissues, and its high level predicted poor prognosis. Loss-of-function assays revealed that RIPK4 silencing suppressed COAD cell growth, induced cell cycle arrest, and enhanced cell apoptosis. In vivo experiments also proved that tumor growth was inhibited by silencing of RIPK4. Luciferase reporter assay validated that RIPK4 was targeted and negatively regulated by miR-575. Western blotting demonstrated that Wnt3a, phosphorylated (p)-GSK-3β, and cytoplasmic and nuclear β-catenin protein levels, β-catenin nuclear translocation, and Cyclin D1, CDK4, Cyclin E, and c-Myc protein levels were reduced by RIPK4 knockdown, which however was reversed by treatment with LiCl, the Wnt/β-catenin pathway activator. LiCl also offset the influence of RIPK4 knockdown on COAD cell growth, cell cycle process, and apoptosis. Finally, RIPK4 downregulation reduced RUNX1 level, which was upregulated in COAD and its high level predicted poor prognosis. RIPK4 is positively associated with RUNX1 in COAD. Overexpressing RUNX1 antagonized the suppression of RIPK4 knockdown on RUNX1, Wnt3a, p-GSK-3β, cytoplasmic β-catenin, nuclear β-catenin, Cyclin D1, CDK4, Cyclin E, and c-Myc levels. Collectively, miR-575/RIPK4 axis repressed COAD progression via inactivating the Wnt/β-catenin pathway through downregulating RUNX1.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Lulu Peng,Zhengwei Zou,Lin Zhou,Lincai Li,Wenming Lu,Cixiang Chen,Yan Xu,Yuyue Liu,Jing Lin,Junsong Ye
Hepatic fibrosis (HF) is a leading cause of death worldwide, yet there is currently no safe and effective treatment available. Canagliflozin, a novel glucose-lowering drug, has been shown to improve non-alcoholic steatohepatitis (NASH). However, its therapeutic effects on HF and the underlying molecular mechanisms remain unclear. In this study, HF was induced in mice via intraperitoneal injections of CCl 4 . Additionally, immortalized hepatic stellate cells (HSCs), including HSC-T6 and LX-2 cells, were used for in vitro experiments. Our findings revealed that Canagliflozin inhibited the activation and proliferation of HSCs, thereby downregulated the expression levels of fibrotic markers (α-SMA and Collagen I), ultimately alleviating HF. Further investigations demonstrated that Canagliflozin inhibits protein phosphatase 2 A (PP2A) activity in HSCs, which in turn prevents PP2A-mediated dephosphorylation of β-catenin and attenuates Wnt/β-catenin signaling. While the Wnt/β-catenin signaling is considered a key mechanism that promote the activation and proliferation of HSCs, it is also a crucial pathway in the development of HF. Moreover, increased activity of PP2A was found to promote the expression of fibrotic markers (α-SMA and Collagen I) in HSCs. In conclusion, our study indicates that Canagliflozin ameliorate HF via inhibiting PP2A-mediated dephosphorylation of β-catenin in HSCs. The inhibition of PP2A in HSCs may represent a potential therapeutic target not only for cancer treatment but also for the management of HF.
研究领域:
药理学
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分子生物学
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肝病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PATHOLOGY RESEARCH AND PRACTICE
·
2025
·
IF 3.2
Ting-Ting Yang,Xin-Xin Ma,Xuan Zhang,Zhen-Qing Han,Shuang Zhang,Qi Wang,Hong-Wei Dong,Jia-Ren Liu
β-Ionone (BI) has shown the potent inhibitory malignant progression of multiple tumors including gastric cancer in vitro and in vivo. However, the mechanism by which BI inhibits gastric cancer remains to be clarified, especially in ferroptosis, which is a new form of programmed cell death. The aim of this study was to investigate whether BI could induce ferroptosis in gastric cancer and the underlying mechanisms. The results manifested that BI obviously inhibited cell viability and increased the Fe 2 + level, total reactive oxygen species (ROS) and lipid ROS levels and the malondialdehyde (MDA) concentrations, but reduced the mitochondrial membrane potential (MMP) and the expression of SLC7A11 and GPX4 in MKN45 cells and AGS cells ( P < 0.05 or P < 0.01). Besides, BI also arrested cell cycle and decreased the expression of Cyclin D1 and CDK4 ( P < 0.05 or P < 0.01). Mechanistically, BI reduced the levels of β-catenin and pGSK-3β/GSK-3β in MKN45 cells and AGS cells ( P < 0.05 or P < 0.01). Nevertheless, pretreatment with lithium chloride (LiCl), an inhibitor of GSK-3β, reversed BI-induced ferroptosis and cell cycle arrested in MKN45 cells ( P < 0.05). In addition, BI effectively inhibited the growth of gastric cancer xenografts and downregulated the levels of GPX4, SLC7A11, PCNA, β-catenin and pGSK-3β/GSK-3β ( P < 0.05 or P < 0.01). Collectively, our study reveals that BI inhibits proliferation of gastric cancer cells by induction ferroptosis via the Wnt/β-catenin signaling pathway and provides a novel therapy for gastric cancer.
研究领域:
肿瘤学
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细胞生物学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Cardiovascular Disorders
·
2024
·Vol. 24
·期 1
·1-11
·
IF 2
Lin Wei,Hou Lianglei,Tang Jialyu,Huang Anwu,Jia Zhuyin
In this study, we sought to investigate the mechanisms of action of miR-195-5p in the osteogenic differentiation of vascular smooth muscle cells (VSMCs), and thereby provide novel insights and a reference for the targeted therapy of arterial media calcification. VSMC differentiation was induced using sodium β-glycerophosphate, and we investigated the effects of transfecting cells with miR-195-5p mimics, vectors overexpressing Smad7, and the Wnt/β-catenin pathway inhibitor (KYA1797K) on VSMC differentiation by determining cell viability and apoptosis, and the mRNA and protein expression of factors associated with osteogenic differentiation and the Wnt/β-catenin pathway. The results revealed that miR-195-5p mimics enhanced the osteogenic differentiation of VSMCs induced by β-glycerophosphate, whereas the overexpression of Smad7 reversed this phenomenon. In addition, KYA1797K was found to promote the effects of Smad7 overexpression. In conclusion, by targeting, Smad7, miR-195-5p promotes the Wnt/β-catenin pathway. and thus the osteogenic differentiation of VSMCs. These findings will provide a reference for elucidating the mechanisms whereby miR-195-5p regulates osteogenic differentiation.
研究领域:
分子生物学
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细胞生物学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）