CELL BIOLOGY INTERNATIONAL
·
2020
·Vol. 44
·期 7
·1503-1513
·
IF 2.571
Peng Yuan,Aidong Zheng,Qing Tang
Tripartite motif protein 25 (TRIM25) expression was altered in various human cancers. Herein, we found that the expression of TRIM25 was elevated in hepatocellular carcinoma (HCC) tissues and cell lines. Knockdown of TRIM25 increased the sensitivity of HCC HepG2 cells to epirubicin (EPI), as indicated by reduced cell viability, enhanced cell apoptosis, and downregulated P-glycoprotein (P-gp) and multiple drug-resistance protein 1 (MRP1). Moreover, TRIM25 knockdown strengthened the effects of EPI on phosphatase and tensin homolog (PTEN) and phosphorylated (p)-AKT. However, overexpression of TRIM25 exerted an opposite effect, weakening the sensitivity of Huh7 to EPI, and obviously increasing PTEN and reducing p-AKT. Most important, all the changes induced by TRIM25 overexpression in Huh7 were reversed with additional treatment of LY294002 (an AKT pathway inhibitor). Notably, coimmunoprecipitation experiments confirmed the interaction between TRIM25 and PTEN. Knockdown of TRIM25 resulted in reduced ubiquitination of PTEN protein. Collectively, our data suggested that TRIM25 enhanced EPI resistance via modulating PTEN/AKT pathway, and targeting TRIM25 may enhance the sensitivity of HCC cells toward chemotherapy drugs.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2026
·Vol. 57
·期 1
·30
·
IF 2.2
Xiang Shouyu,Liu Wei,Tang Cheng,Xie Chuhai,Hu Hailan,Zhou Jianhui,Cao Yanming,Ling Long
Bone marrow mesenchymal stem cells (BMSCs) play a significant role in bone defect repair. Currently, the limited survival and function of transplanted BMSCs pose major obstacles to tissue repair mediated by these cells. Therefore, the exploration of BMSCs transplantation activity has become an urgent clinical problem. In this experiment, we constructed lentiviral vectors with overexpression and silencing of miR-19b-3p and utilized a rat fracture model. The effects of BMSCs proliferation were examined using CCK-8, the Annexin V-FITC apoptosis kit and TUNEL assay, the effects of BMSCs osteogenic differentiation were detected using ALP and Alizarin red staining. Furthermore, Western blotting and qRT-PCR were employed to examine the expression of key proteins in the PTEN/Akt/mTOR signaling pathway and autophagy-related proteins. Moreover, the impact of miR-19b-3p on bone microstructure was assessed using Micro CT, HE, Safranin O/Fast Green, as well as Masson staining, and Immunohistochemistry analysis examined PTEN, p62 and Runx2 expression levels on fracture site. By constructing lentiviral vectors with overexpression and silencing of miR-19b-3p, we found that silencing miR-19b-3p significantly promoted the proliferation as well as the osteogenic differentiation of BMSCs under hypoxia. Western blotting and qRT-PCR results showed that silencing miR-19b-3p significantly increased PTEN, LC3, and Beclin1 expression while decreasing p-Akt, p-mTOR, and p62 expression. Furthermore, by constructing the fracture rats and administering hypoxia-treated BMSCs transfected with miR-19b-3p via tail vein injection, we found that silencing miR-19b-3p obviously increased the formation of trabecular and promoted the healing of the fractures. Immunohistochemistry analysis showed that silencing miR-19b-3p upregulated PTEN and Runx2 expression levels and suppressed p62 expression with statistical significance. In summary, these findings suggest that miR-19b-3p may regulate BMSCs’ autophagy and osteogenic differentiation under hypoxia via the PTEN/Akt/mTOR signaling pathway, thereby promoting fracture healing and providing a potential target for the treatment of fractures.
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高影响因子
TOXICOLOGY LETTERS
·
2018
·
IF 3.166
Lin Li,Jiahui Cui,Zi Liu,Xuejiao Zhou,Zengqiang Li,Yang Yu,Yuanyuan Jia,Daiying Zuo,Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response. Prolonged exposure of cells to AgNPs damaged calcium (Ca 2+ ) homeostasis, increased the length of contact sites between the ER and mitochondria, altered IP 3 R function by the increased levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the ER and enhanced mitochondrial Ca 2+ uptake. Finally, Ca 2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death. Our results suggest that caution should be exercised in the use of AgNPs in humans.
研究领域:
纳米技术
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细胞生物学
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毒理学
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神经科学
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PubMed
高影响因子
Molecular Medicine Reports
·
2021
·Vol. 24
·期 2
·1-12
·
IF 2.952
Linmei Zhu,Ruixia Chen,Chunlin Jiang,Qingsheng Xie,Wenshuai Zhao,Xiaohong Gao,Haiming Huang
Long non‑coding RNA ILF3 divergent transcript (ILF3‑AS1) displays a tumor‑suppressing effect. StarBase predicted that the potential target microRNA (miR) of ILF3‑AS1 was miR‑454‑3p; therefore, the present study investigated the effect of ILF3‑AS1 and its target miR‑454‑3p on cervical cancer (CC). Gene Expression Profiling Interactive Analysis was used to predict the expression of ILF3‑AS1 in CC and the overall survival rate of patients. The present study demonstrated that ILF3‑AS1 expression was significantly downregulated in human CC tissues and cells compared with adjacent tissues (ANTs) and normal cervical epithelial cells (NCEs), respectively. Patients with CC with high ILF3‑AS1 expression displayed higher survival rates compared with patients with low ILF3‑AS1 expression. Cell viability, apoptosis, migration and invasion were detected by performing Cell Counting Kit‑8, flow cytometry, wound healing and Transwell assays, respectively. Compared with the negative control (NC) group, ILF3‑AS1 overexpression significantly inhibited CC cell viability and migration, but significantly increased CC cell apoptosis. Moreover, ILF3‑AS1 overexpression significantly upregulated E‑Cadherin expression levels, but significantly downregulated N‑Cadherin and snail family transcriptional repressor 1 expression levels compared with the NC group. miR‑454‑3p expression was negatively correlated with ILF3‑AS1, and highly expressed in CC tissues and cells compared with ANTs and NCEs, respectively. PTEN, which was predicted and verified as the target gene for miR‑454‑3p, was significantly downregulated in CC tissues and cells compared with ANTs and NCEs, respectively. ILF3‑AS1 expression was positively correlated with PTEN expression, and ILF3‑AS1 overexpression partially reversed the inhibitory effect of miR‑454‑3p on PTEN expression. In conclusion, the present study indicated that ILF3‑AS1 inhibited CC cell proliferation and migration, and promoted CC cell apoptosis by inhibiting epithelial‑mesenchymal transition, and ILF3‑AS1 overexpression partially reversed the inhibitory effect of miR‑454‑3p on PTEN expression.
研究领域:
分子生物学
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肿瘤学
·
细胞生物学
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PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2023
·Vol. 124
·期 4
·557-572
·
IF 4
Juan Gu,Xu Chu,Yujia Huo,Chaoyi Liu,Qingge Chen,Shengnan Hu,Yanyan Pei,Pu Ding,Sen Pang,Ming Wang
Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症生物学
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PubMed
高影响因子
NUTRITIONAL NEUROSCIENCE
·
2025
·
IF 3.6
Jiahao Liu,Jiawei Li,Yuanyuan Liu,Ruici Liu,Liya Fang,Zhimei Jiang,Lei Liu,Luchuan Wang,Chao Gong,Deming Kong,Ruting Fu,Pei Zeng,Jin Guo,Shaobo Zhou
Objective Epilepsy treatments often lead to vitamin D (VitD) deficiency. Although vitamin D₃ (VitD3) has been shown to reduce epileptic symptoms by 43%, its preventive effects remain unclear. This study investigated the potential of VitD pretreatment in two common acute epilepsy mouse models and explored its effects on seizure severity, latency, and molecular mechanisms involving calcium-sensing receptor (CaSR), phosphatase and tensin homolog (PTEN), and autophagy.Methods Mice were randomly divided into nine groups (n = 15). VitD or vehicle was administered 40 min before pentylenetetrazole (PTZ) or kainic acid (KA) given intraperitoneal injection (i.p). Seizure behavior and electroencephalograms (EEGs) were recorded for 60 min. After 24 h, hippocampal tissues were analyzed histologically and assessed for expression of autophagy-related proteins, CaSR, and PTEN.Results Both PTZ and KA induced acute seizures (Racine Grade IV+), with corresponding high-amplitude EEG spikes, neuronal damage, and mossy fiber sprouting. CaSR and autophagy markers were upregulated, while PTEN was downregulated, especially in the KA group. VitD pretreatment reduced seizure frequency, prolonged latency, alleviated hippocampal damage, downregulated CaSR and autophagy markers, and upregulated PTEN. These effects were milder than those of valproate. Combined VitD and Oroxin B treatment further improved outcomes.Conclusions (1) PTZ-induced seizures increased CaSR and decreased PTEN, triggering autophagy and worsening symptoms. (2) KA-induced epilepsy caused more severe damage with stronger autophagy activation. (3) VitD pretreatment mitigated seizures by modulating CaSR, PTEN, and autophagy, showing greater efficacy in the PTZ model.
研究领域:
神经病学
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分子生物学
·
药理学
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PubMed
高影响因子
Cell Death & Disease
·
2025
·Vol. 16
·期 1
·1-16
·
IF 9.6
Jing Yukai,Zhang Yunfei,Wang Xiaocui,Wang Yufen,Hu Ying,Wen Bin,Dai Xin,Duan Xuemei,Li Haonan,Dong Shumin,Yan Ze,Fan Yufeng,Wang Cong-yi,Liu Xiansheng,Zhang Ruiping
Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the overproduction of autoantibodies and type I interferon, which damages its own tissues, causing multiple organ damage. B cells are thought to play a major role in the pathogenesis of SLE. As a DNA methylation reader, Methyl-CpG-binding domain protein 2 (MBD2) has been extensively studied in the contexts of innate immunity, adaptive immunity, and autoimmune diseases. However, its specific role in B cells and SLE remains unexamined. Herein, we found that MBD2 was highly expressed in B cells of SLE patients and positively correlated with disease activity. Knockout of MBD2 in B cells disturbed B-cell differentiation, dampened B-cell activation, B-cell receptor (BCR) signaling, and T-cell-dependent humoral immune responses in mice. What’s more, MBD2 deficiency effectively attenuated lupus-like symptoms, reduced the germinal center responses, and decreased anti-dsDNA antibodies in lupus model mice. Mechanistically, MBD2 selectively bound to the methylated CpG of Lef-1 induced by IFN-α, inhibiting the transcription and expression of Lef-1 , which repressed Pten transcription and expression, thereby promoting PI3K-Akt-mTOR signaling. This study first demonstrated the role of MBD2 in the pathogenesis of SLE and provided a new target for SLE.
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高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Ye Zhou,Meng Zhang,Zhilei Zhang,Yuming Jia,Chong Zhang,Li Peng
Hydrazinocurcumin (HZC), a curcumin analogue, serves as a tumor suppressor in breast cancer and lung cancer. In this study, we investigate the role and mechanism of HZC in regulating HepG2 cell apoptosis and tumorigenicity, and its synergistic effects with 5-fluorouracil (5-Fu). HepG2 cells were treated with HZC and/or 5-Fu to analyze the possible synergistic effects on cell proliferation, apoptosis and cell cycle distribution in vitro using EdU staining, Hoechst staining and flow cytometry, respectively. For mechanistic investigation we used pic, a phosphatase and tensin homolog (PTEN) inhibitor, and in other studies assessed the expression pattern of PTEN and PI3K/Akt signaling pathway-related genes. Additionally, we tested in vivo effects of HZC and 5-Fu treatment on growth of HepG2 cell tumors in nude mice. We found that HZC or 5-Fu induced apoptosis and repressed proliferation of HepG2 cells by upregulating the expression of PTEN and disrupting the PI3K/Akt signaling pathway activation. Moreover, HZC had a higher pro-apoptotic effect than 5-Fu. HZC and 5-Fu induced HepG2 cell apoptosis and inhibited their tumorigenicity in vivo . Inhibition of PTEN expression activated the PI3K/Akt signaling pathway and reversed the protective effects of HZC or 5-Fu. Thus, HZC and 5-Fu increase PTEN, which blocks the PI3K/Akt signaling pathway, ultimately inducing HepG2 cell apoptosis. Importantly, the synergistic combination of HZC and 5-Fu may present promising strategy for the treatment of HCC.
研究领域:
肿瘤学
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分子生物学
·
药理学
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高影响因子
EXPERIMENTAL CELL RESEARCH
·
2021
·
IF 3.905
Yiming Li,Yi He,Guanhui Chen,Ziqing Huang,Chen Yi,Xiliu Zhang,Feilong Deng,Dongsheng Yu
abstract Dental implant surgery is currently a routine therapy for the repair of missing dentition or dentition defects. Both clinical and basic research have elucidated that oxidative stress caused by the accumulation of reactive oxygen species (ROS) for various reasons impairs the process of osteointegration after dental implantation. Therefore, the osteogenic micro-environment must be ameliorated to decrease the damage caused by oxidative stress. Selenomethionine (SEMET) has been reported to play an important role in alleviating oxidative stress and accelerating cell viability and growth. However, it remains unclear whether it exerts protective effects on bone-marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress. In this study, we explored the influence of selenomethionine on the viability and osteogenic differentiation of BMSCs under oxidative stress and the underlying mechanisms. Results showed that 1 μM selenomethionine was the optimum concentration for BMSCs under H 2 O 2 stimulation. H 2 O 2 -induced oxidative stress suppressed the viability and osteogenic differentiation of BMSCs, manifested by the increases in ROS production and cell apoptosis rates , and by the decrease of osteogenic differentiation-related markers. Notably, the aforementioned oxidative damage and osteogenic dysfunction induced by H 2 O 2 were rescued by selenomethionine. Furthermore, we found that the PTEN expression level was suppressed and its downstream PI3K/AKT pathway was activated by selenomethionine. However, when PTEN was stimulated, the PI3K/AKT pathway was down-regulated, and the protective effects of selenomethionine on BMSC osteogenic differentiation diminished, while the inhibition of PTEN up-regulated the protective effects of selenomethionine. Together, these results revealed that selenomethionine could attenuate H 2 O 2 -induced BMSC dysfunction through an antioxidant effect, modulated via the PTEN/PI3K/AKT pathway, suggesting that selenomethionine is a promising antioxidant candidate for reducing oxidative stress during the process of dental implant osteointegration.
研究领域:
牙科学
·
干细胞生物学
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药理学
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分子生物学
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PubMed
高影响因子
BIOMARKERS
·
2026
·
IF 1.9
Yang Jiang,Xiaosheng Jin
Background PM2.5-induced COPD lacks effective therapies due to unclear pathogenesis. This study explores the role of miR-122 and PTEN in PM2.5-related COPD.Methods Using a combination of in vitro and in vivo assays, including cigarette smoke extract (CSE)-induced NR8383 cells and a rat smoke model, combined with MTT, qPCR, flow cytometry, WB, HE staining, Masson staining, HIC, and TUNEL assays, we investigated the role of microRNA-122 (miR-122) and phosphatase and tensin homolog (PTEN) in the molecular mechanisms underlying PM2.5-induced COPD.Results Our findings demonstrate that CSE-induced the down-regulated expression of miR-122 leads to the activation of PTEN, which in turn regulates the AKT signaling pathway in NR8383 cells. This modulation results in decreased expression of B-cell lymphoma 2 (BCL2), promoting cell apoptosis. Besides, the result from a rat model of COPD exposed to smoke also confirms this molecular axis which ultimately exacerbating COPD. Specifically, compared with the control, there is significant pulmonary structural damage in model rats exposed to PM2.5, including enlarged alveolar intervals, increased alveolar cavity size, pulmonary fibrosis, and evidence of alveolar destruction with concomitant parabronchial inflammation.Conclusion Our research reveals novel insights of PM2.5-induced COPD and proposes the miR-122/PTEN pathway as a potential therapeutic target.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yawen Yu,XinLiu Duan,Xiaorong Wang,Mingyan Yang,Ling Weng,Dalei Li,Teng Liu,Baifang Gong,Zhixia Wang,Huaying Fan
Ginseng-derived exosome-like nanoparticles (GENs) have been considered as new candidates for tumor therapy. However, maintaining the retention and stability of exosomes in vivo is a major challenge in clinical application of GENs. Here, we prepared hydrogels using modified hyaluronic acid (HA) and carboxymethyl chitosan (CMCS). We investigated whether the combination of GENs with hydrogels could improve the stability of GENs and enhance their retention in tumor tissues, thereby enhancing their tumor therapeutic effect. In vitro experiments showed that hydrogels significantly increased the uptake of GENs by cells and increased tumor apoptosis rate. In vivo experiments showed that hydrogels significantly increased the retention of GENs in tumor tissues and improved the antitumor ability of GENs. Meanwhile, we evaluated the anti-tumor mechanism of GENs. The results showed that GENs and GENs@Hydrogels induced 4T1 cell apoptosis through the PTEN/PI3K/Akt/mTOR pathway and caspase-dependent pathway. In addition, GENs and GENs@Hydrogels down-regulate PD-L1 level in tumor tissues, up-regulate MHC-I level, and increase the abundance of CD8+T cells, which have immune regulation ability. In conclusion, GENs@Hydrogels has been shown to be a successful candidate for the treatment of breast cancer (BC) with its promising potential to modulate immunity and inhibit tumor progression.
研究领域:
生物医学工程
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肿瘤学
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药理学
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高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2020
·
IF 3.347
Cong Zhang,Lei Sheng,Ming Yuan,Junjie Hu,Yan Meng,Yong Wu,Liang Chen,Huifan Yu,Shan Li,Guohua Zheng,Zhenpeng Qiu
Orlistat (Xenical™), a US Food and Drug Administration (FDA)-approved anti-obesity drug, shows efficacy against multiple tumor types, including hepatocellular carcinoma (HCC), due to its ability to inhibit fatty acid synthase (FASN) activity. However, whether orlistat affects hepatocellular malignant transformation during hepatocarcinogenesis in vivo is unknown. This study assessed the antisteatotic and antitumorigenic efficacy of orlistat in a rapid HCC FVB/N mouse model established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Human hepatoma cell lines were used for mechanical validation in vitro . Hematoxylin and eosin staining, immunohistochemistry, and immunoblotting were applied for the mechanistic investigation. The results revealed that when orlistat was administered in the early stage of AKT/c-Met-triggered hepatocarcinogenesis, it resulted in the elimination of hepatic tumor burden. Mechanistically, orlistat efficiently elevated PTEN expression and suppressed AKT/SREBP1/FASN signaling both in vivo and in vitro , impairing AKT/c-Met-driven de novo lipogenesis and aberrant proliferation. Altogether, this study demonstrates the antilipogenic and antiproliferative efficacy of orlistat in hepatocarcinogenesis, suggesting that orlistat may be beneficial for the treatment of HCC, especially in NAFLD-related HCCs featuring activated AKT/mTOR cascade and increased lipogenesis in livers.
研究领域:
肿瘤学
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肝病学
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分子生物学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）