JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2018
·Vol. 22
·期 5
·2774-2790
·
IF 4.302
Qiongli Su,Ting Tao,Lei Tang,Jun Deng,Kwame Oteng Darko,Sichun Zhou,Mei Peng,Shanping He,Qing Zeng,Alex F. Chen,Xiaoping Yang
Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non-muscle-invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down-regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p-AMPK and p-STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan-Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder cancer cells and tissues, and down-regulation of PKM2 enhanced the sensitivity of THP in vitro. Activation of AMPK is essential for THP to exert anti-bladder cancer activities. On the other hand, down-regulating PKM2 activates AMPK and inhibits STAT3, correlated with THP sensitivity. Compared with THP alone (400 μmol L −1 , 50 μL), the combination with metformin (60 mmol L −1 , 50 μL) stopped growth of bladder cancer completely in vivo (combination group VS normal group P = .078). Down-regulating the expression of PKM2 enhances the anticancer efficiency of THP. This study provides a new insight for improving the chemotherapeutic effect of THP.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2022
·Vol. 14
·期 9
·
IF 4.767
Jiao Liu,Xiaoxuan Wang,Yuan Cheng,Yinghua Yu,Maofang Zhao,Jie Huang,Peiquan Yu,Qian Fu,Yilin Song,Yi Liu
Background: H2S is the third gas transmitter affecting the growth, reproduction and survival of cancer cells. However, the H2S anticancer and antitumor mechanism still needs to be further studied. Methods: Here, FHS-1 was synthesized utilizing excited-state intramolecular proton transfer to detect H2S in MCF-7 cells, and investigated the effects of varying concentrations NaHS on apoptosis. Results: The study found that FHS-1 detects H2S levels with high selectivity and pH stability and that H2S may regulate apoptosis in MCF-7 cells through the p53/mTOR/STAT3 pathway. Conclusion: Researching the influence of H2S on apoptosis can serve as a theoretical foundation for future research into H2S-related anticancer medicines, and the H2S probe can be used as an effective cancer screening tool.Graphical abstract
研究领域:
癌症生物学
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细胞信号传导
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药物化学
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PubMed
高影响因子
JOURNAL OF GENE MEDICINE
·
2021
·Vol. 23
·期 6
·e3337
·
IF 4.565
Bo Wang,Ye Lu,Eryan Feng
Background Endometrial carcinoma (EC) development is associated with dysregulated circular RNA profiles. The purpose of the current research is to study the role and mechanism of hsa_circ_0001610 (circ_0001610) in EC progression. Methods circ_0001610, microRNA (miR)-646, and signal transducer and activator of transcription 3 (STAT3) expression levels were measured in EC. Functional analyses were performed using Cell Counting Kit-8, colony formation, transwell, wound healing, flow cytometry, glycolysis, and xenograft analyses. Binding association was evaluated with dual-luciferase reporter assay. Results circ_0001610 levels were upregulated in EC samples ( n = 30) and cells. circ_0001610 interference restrained cell proliferation, migration, and invasion, and promoted apoptosis. circ_0001610 downregulation constrained glycolysis through reducing glucose consumption, lactate production, and levels of adenosine triphosphate, extracellular acidification, hexokinase 2, and lactate dehydrogenase A, and increasing oxygen consumption rate. miR-646 is targeted by circ_0001610, and miR-646 inhibition attenuated interference of circ_0001610-mediated suppression of EC development. STAT3 was modulated by miR-646, and miR-646 upregulation restrained EC progression by decreasing STAT3. circ_0001610 silencing reduced STAT3 levels by sponging miR-646 and reduced the growth of xenograft tumor established by EC cells. Conclusion circ_0001610 knockdown represses EC progression through modulating the miR-646-STAT3 axis.
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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Ning-Ning Huang,Ping-An Jian,Jia-Yu Du,Wen-Na Cai,Tian-Ning Yang,Zhi-Juan Wang,Shi-Yong Zhu,Kai Guo,Jin-Long Li,Chi-Chiu Wang,Xue-Nan Li
Global health issues have been heightened by di-(2-ethylhexyl) phthalate (DEHP), a commonly utilized plasticizer, due to its liver toxicity and potential to cause liver damage. Ferroptosis, a type of nonapoptotic cell death reliant on iron, is associated with multiple liver disorders. This research aimed to explore the role and mechanisms of ferroptosis in DEHP-induced liver toxicity in chickens. In vivo experiments showed that DEHP exposure caused liver damage. Transcriptomic analysis revealed that DEHP exposure activated ferroptosis and significantly upregulated myo-inositol oxygenase (MIOX) expression. Subsequent in vitro experiments using LMH cells revealed that reducing MIOX levels diminished ferroptosis caused by mono- (2-ethylhexyl) phthalate (MEHP), DEHP’s main metabolite, through the stimulation of the STAT3 signaling pathway. Our findings highlight the important role of MIOX in DEHP-induced liver injury via STAT3 signaling pathway. This study provides new evidence that MIOX is a potential therapeutic target for iron toxicosis associated liver diseases.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 4
·2018
·
IF 6.208
Yan Zhang,Pei Ma,Zhiguang Duan,Yannan Liu,Yu Mi,Daidi Fan
Lung adenocarcinoma (LAC) is a common lung cancer with a high malignancy that urgently needs to be treated with effective drugs. Ginsenoside Rh4 exhibits outstanding antitumor activities. However, few studies reported its effects on growth, metastasis and molecular mechanisms in LAC. Here, Rh4 is certified to show a strong anti-LAC efficiency in vitro and in vivo. Results of flow cytometry and Western blot are obtained to exhibited that Rh4 markedly restrained cellular proliferation and colony formation by arresting the cell cycle in the G1 phase. Results from a wound healing assay and transwell assays demonstrated that Rh4 is active in the antimigration and anti-invasion of LAC. The analysis of Western blot, immunofluorescence and RT-qPCR confirmed that Rh4 reverses the epithelial–mesenchymal transition (EMT) through upregulating the gene expression of E-cadherin and downregulating that of snail, N-cadherin and vimentin. In vivo results from immunohistochemistry show consistent trends with cellular studies. Furthermore, Rh4 suppresses the Janus kinases2/signal transducer and activator of the transcription3 (JAK2/STAT3) signaling pathway stimulated by TGF-β1. Silencing the STAT3 signal or co-treating with AG490 both enhanced the EMT attenuation caused by Rh4, which revealed that Rh4 suppressed EMT via inhibiting the JAK2/STAT3 signaling pathway. These findings explore the capacity and mechanism of Rh4 on the antimetastasis of LAC, providing evidence for Rh4 to LAC therapy.Keywords:ginsenoside Rh4;lung adenocarcinoma;metastasis;cell cycle;JAK/STAT signaling
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
DNA AND CELL BIOLOGY
·
2022
·Vol. 41
·期 4
·424-436
·
IF 3.55
Feng Chi,Fang Qiu,Xiaoming Jin,Long Chen,Guijin He,Sijia Han
Breast cancer (BC) is one of the most frequently occurring malignant tumors in female adults. The long intergenic nonprotein coding RNA 00982 (LINC00982) has been regarded as a cancer suppressor in several human cancers. However, the function and the underlying mechanisms of LINC00982 have not been studied in BC. The present study found that LINC00982 was significantly downregulated in BC tumor tissues, and the low LINC00982 level predicts a poor prognosis of BC. Through the overexpression and suppression of LINC00982 in two BC cell lines, we found that LINC00982 could inhibit cell proliferation, migration, and invasion by suppressing the activity of the signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF-κB) signal pathway. Furthermore, luciferase reporter assay has been used to verify that LINC00982 functions as a molecular sponge for miR-765, which could target DPF3. The relative expression of miR-765 decreased with LINC00982 overexpressing, and DPF3 increased at the same time.In addition, the suppression of cell malignant phenotype caused by overexpression of LINC00982 can be reversed by inhibition of DPF3. To verify the function of LINC00982 in vivo, the BC cells were implanted in nude mice and the results suggested the tumor growth and malignant phenotype were suppressed by LINC00982. In this study, we prove that LINC00982 regulates the growth and development of BC through STAT3/NF-κB signal pathway, mediated by the miR-765/DPF3 axis. LINC00982 may function as a target molecule to take part in the prognosis and therapy of BC.
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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DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
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2022
·
IF 10.334
Bei Yan,Panpan Liu,Xiaoqin Yi,Jie Li,Nian Liu,Wu Zhu,Yehong Kuang,Xiang Chen,Cong Peng
Background Psoriasis is a chronic inflammatory disease , with lesions mainly manifesting as scaly erythematous plaques. The mild or moderate of psoriasis is the main type of patients in hospital, and topical application remains the preferred treatment option for psoriasis therapy, therefore, the development of novel topical agents has an essential role in psoriasis therapy. Objective To identify potential drugs for psoriasis topical treatment. Methods We performed drug screening by Imiquimod (IMQ)-induced psoriatic like inflammation in mouse model, followed mouse epidermis by RNA-seq to find the key molecules affecting the drug. The qRT-PCR, WB were performed to test mRNA and protein expression, and Chip assay had been conducted to examine Stat3 bound to promoter of FABP5. Results In this study, we identified VX-509, which topical application significantly attenuated IMQ-induced psoriatic like inflammation in mouse model. And then, we verified Epidermal Fatty acid binding protein (E-FABP/FABP5) was significantly decreased in VX-509 treated mouse epidermis by RNA-seq. FABP5 is a key molecule in lipid metabolism, administration of FABP5 inhibitor or knock down of FABP5 expression remarkably abrogated psoriatic inflammation as well as lipid metabolism. Mechanistically, our finding showed that VX-509 blocked IL-22 induced signaling pathway, particular in activation of Stat3. Furthermore, we identified Stat3 is a transcriptional factor associated with FABP5 promoters and VX-509 treatment remarkably attenuated IL-22-induced FABP5 expression through Stat3 in KCs. Conclusions This study demonstrated administration of VX-509 is a potential promising topical drug for treatment of psoriasis, FABP5 is a critical targeted molecule in psoriasis therapy.
研究领域:
皮肤科
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药理学
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分子生物学
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炎症
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DOI
PubMed
高影响因子
Cancer Cell International
·
2020
·Vol. 20
·期 1
·1-16
·
IF 4.175
Tang Ling,Long Jing,Li Keke,Zhang Xu,Chen Xiang,Peng Cong
Background Fyn has been documented to have oncogenic features in multiple tumors, which might be a potential therapeutic target, however, few studies on the function role of Fyn and its specific inhibitors in melanoma. Methods We investigated the impacts of Fyn and its inhibitor Lj-1-60 on melanoma through bioinformatics analysis, western blot, cell viability, cell cycle and apoptosis and xenograft tumor model as well as immunohistochemical staining. Pull-down and in vitro kinase assay were used to demonstrate Lj-1-60 targeting Fyn. Transcriptome sequencing and RT-PCR were adopted to confirm the potential mechanisms of Lj-1-60 in melanoma. Results Our findings showed that Fyn was overexpressed in melanoma cells and knocked down of Fyn suppressed the proliferation of melanoma cells. To identify the potential inhibitors of Fyn, our in-house library including total of 111,277 chemicals was conducted to vitro screening, among those compounds, 83 inhibitors were further detected to explore the effect on melanoma cells growth and discovered a novel chalcone derivative Lj-1-60 that exhibited low cellular toxicity and high anti-tumor efficacy. Lj-1-60 directly was associated with Fyn and inhibited the Fyn kinase activity with Stat3 as substrate. What’s more, Lj-1-60 suppressed the proliferation of melanoma in vitro and in vivo through inducing cell cycle arrest and apoptosis. Moreover, the activation of Stat3 had also been abrogated both in Lj-1-60 treated melanoma cells or Fyn knocked down cells. Conclusion Our study revealed a novel Fyn inhibitor that could significantly suppress melanoma growth, which is a promising potential inhibitor for melanoma treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
·
IF 2.65
Li Li,Ru Liu,Jing He,Jing Li,Juan Guo,Yun Chen,Ke Ji
Objective. Microglial BV-2 cells are activated in the brain following insomnia. Naringin (NAR) is a polymethoxylated flavonoid that is also commonly found in citrus fruits and is known for its antioxidant potential. However, the effect of NAR on microglial cells has rarely been studied in the brain of an organism after insomnia. This study aimed to investigate the effects and potential mechanisms of action of NAR on microglial cell activation and inflammation. Methods. BV-2 cells were obtained from the China Center for Type Culture Collection and randomly divided into five treatment groups: control, model, NAR (10 μM), WP1066 (5 μM), and NAR + WP1066. With the exception of the control group, all groups were stimulated with LPS (1 μg/mL) for 6 h. CCK8 was used to quantify cell viability and a scratch test was performed to detect cell migration. The expression levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), nterleukin 10 (IL-10), and insulin like growth factor (1IGF-1) were measured by ELISA. Western blotting was performed to determine the levels of p-STAT3 and p-JAK. The Focalcheck™ Thin-Ring Fluorescent Microspheres kit was used to detect cell phagocytosis. Immunofluorescence was used to observe the expression of iNOS and arginase1 in BV-2 cells. Results. Compared with the control group, cell migration, cell viability, and the expression of IL-1β, IL-6, TNF-α, and iNOS were significantly increased in the model group, whereas the expression levels of IL-10, IGF-1, and arginase 1, as well as cell phagocytosis were reduced. With the increase in NAR concentration, cell migration, cell viability, the expression levels of IL-1β, IL-6, TNF-α, and iNOS decreased, while the expression of IL-10, IGF-1, and arginase 1 increased. Compared with the control group, p-STAT3, and p-JAK expression in the model group were significantly increased (P<0.05). Compared with the model group, the expression of p-STAT3 and p-JAK in the NAR, NAR + WP1066, and WP1066 groups was significantly decreased (). Conclusion. NAR treatment inhibited the proliferation, migration, and inflammation of BV-2 cells as well as the activation of microglia to the M1 phenotype. Conversely, NAR treatment promoted the activation of microglia to the M2 phenotype and enhanced the phagocytic function of BV-2 cells by regulating the activity of the JAK/STAT3 pathway.
研究领域:
神经科学
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免疫学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR PROBES
·
2019
·
IF 2.511
Danning Lou,Jun Wang,Xiaohang Wang
Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide and a major public health concern that is associated with grave consequences. Systemic complexity and feedback processes among diverse drivers of the depression disorder contribute to the considerable variation in responses to the treatment of depression . Dysfunctional microRNA (miRNA) is involved in MDD. miR-124 is enriched in the brain and may be critical in neuronal differentiation . Previous studies have shown the value of miRNA-124 as a putative therapeutic target and a biomarker for major depression. However, the detailed mechanism of action of miR-124 in depression remains poorly understood. Here, we observed that miR-124 was downregulated in the hippocampus of mice with chronic unpredictable mild stress (CUMS). Restoration of miR-124 expression significantly attenuated depressive-like behavior and inhibited microglial activation induced by CUMS. Mechanistically, miR-124 directly targeted signal transducer and activator of transcription 3 (STAT3) in BV2 cells; in addition, upregulation of miR-124 inhibited the increase of inducible nitric oxide synthetase and proinflammatory cytokines , including IL-6, IL-1β, TNF-α, and MCP-1, in LPS-stimulated BV2 cells. The collective data suggest that dysfunction of miR-124 may be a foundation for the development of depression by promoting microglial activation.
研究领域:
神经科学
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分子生物学
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精神病学
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DOI
PubMed
高影响因子
American Journal of Translational Research
·
2019
·
IF 3.266
Hua Liu,Xiao-De Feng,Beng Yang,Rong-Liang Tong,Yue-Jie Lu,Di-Yu Chen,Lin Zhou,Hai-Yang Xie,Shu-Sen Zheng,Jian Wu
Dimethyl fumarate (DMF) is generally used to treat psoriasis and multiple sclerosis. In the present study, we aimed to investigate the effects of DMF on hepatocellular carcinoma progression and its mechanism of action. In vitro , cell viability was examined using CCK-8 assay; cell cycle was analyzed by flow cytometry; angiogenesis was detected using tube formation assay; and autophagic flux assay results were examined using fluorescence microscopy. We also used western blotting to explore the potential mechanisms. In vivo , tumor xenograft experiment was performed with nude mice, and liver function, renal function, and routine blood counts were assessed using biochemical tests. Dimethyl fumarate inhibited tumor growth and angiogenesis in hepatocellular carcinoma, both in vitro and in vivo . Dimethyl fumarate decreased autophagy in hepatocellular carcinoma cells. Treatment with DMF activated SOCS3, which led to repression of JAK1 and STAT3 phosphorylation. DMF inhibited cell proliferation, angiogenesis, and autophagy via activation of the SOCS3/JAK1/STAT3 signaling pathway. This finding may provide a novel approach for the treatment of hepatocellular carcinoma.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2026
·
IF 4.5
Jing Chen,HongYinLong Cui,MingKui Zhao,XiaoHan Du,Wen Chen
Alpk1 overexpressed in microglia of SE models. • Knockdown of Alpk1 alleviated the symptoms in epileptic rats. • Knockdown of Alpk1 represses M1-microglial activation. • Effects of Alpk1 knockdown are via suppressing JAK2/STAT3 signaling. Background Epilepsy is a chronic brain disorder characterized by recurrent, highly synchronous abnormal neuronal discharges leading to cerebral dysfunction. This study investigates the role of alpha kinase 1 (ALPK1), a pattern recognition receptor, in epilepsy. Methods ALPK1 expression and distribution were analyzed using the GSE190452 dataset and a pilocarpine-induced rat model. An adeno-associated virus delivering Alpk1 shRNA was injected intra-hippocampally into model rats, followed by seizure monitoring. Pathological changes were assessed via hematoxylin and eosin and Nissl staining. Primary microglia and BV2 cells transfected with Alpk1 siRNA were stimulated with kainic acid. Immunofluorescence, quantitative real-time polymerase chain reaction, and Western blot were used to evaluate M1 microglial marker and pro-inflammatory cytokines. Gene Set Enrichment Analysis (GSEA) was performed to identify potential signaling associated with Alpk1 function. Results ALPK1 was widely distributed and highly expressed in epileptic microglia. Alpk1 knockdown alleviated seizure symptoms in rats, including hippocampal damage, Nissl body loss, reduced Racine scores, and decreased daily seizure frequency and duration. Both in vivo and in vitro , Alpk1 knockdown downregulated the M1 marker inducible nitric oxide synthase and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6). GSEA indicated Alpk1 activates Janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) signaling. Stat3 overexpression reversed the inhibitory effects of Alpk1 knockdown on M1 activation and inflammation. Conclusion ALPK1 is highly expressed in epileptic microglia. Silencing Alpk1 alleviates M1-microglial activation and inflammation in epilepsy by inhibiting the JAK2/STAT3 signaling.
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高影响因子
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