JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2018
·Vol. 37
·期 1
·1-11
·
IF 6.217
Dai Xuanxuan,Yin Changtian,Zhang Yi,Guo Guilong,Zhao Chengguang,Wang Ouchen,Xiang Youqun,Zhang Xiaohua,Liang Guang
Background Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer. Patients with TNBC have poor clinical outcome as they are non-responsive to current targeted therapies. There is an urgent need to identify new therapeutic targets and develop more effective treatment options for TNBC patients. Osthole, a natural product from C. monnieri, has been shown to inhibit certain cancer cells. However, the mechanisms of action as well as its effect on TNBC cells are not currently known.Methods We investigated the effect of osthole in cultured TNBC cells as well as in a xenograft model of TNBC growth. We also used a high-throughput proteomics platform to identify the direct binding protein of osthole.Results We found that osthole inhibited the growth of a panel of TNBC cells and induced apoptosis in both cultured cells and TNBC xenografts. We used a high-throughput proteomics platform and identified signal transducer and activator of transcription 3 (STAT3) as a potential binding protein of osthole. We further show that osthole suppressed STAT3 in TNBC cells to inhibit growth and induce apoptosis. Overexpressing STAT3 in TNBC reduced the effectiveness of osthole treatment.Conclusion sThese results provide support for osthole as a potential new therapeutic agent for the management of TNBC. Moreover, our results indicate that STAT3 may be targeted for the development of novel anti-TNBC drugs.
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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PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2025
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IF 4.2
Shibo Zhu,Sunwei Tang,Zijie Ye,Wei Jia
One of the most prevalent male urogenital anomalies is hypospadias. The general etiology of hypospadias is still not completely clear, despite the fact that the number of patients with the hypospadias is rising. HNF-1α was predicted as the most activated upstream regulator of severe hypospadias in our previous research. Our study aims to investigate the mechanism by which HNF-1α regulates hypospadias. We found that HNF-1α was highly expressed in hypospadias tissues, and was positively associated with fibrinogen related genes FGA and FGB, respectively. In animal experiments, silencing of HNF-1α resulted in a more narrow urethral groove, and a decreased periurethral pathologic fibrosis. Meanwhile, the inflammation cytokines and oxidative stress related factors were significantly reduced after inhibition of HNF-1α expression. In addition, the protein levels of STAT3, FGA and FGB were also depressed after HNF-1α knockdown. Mechanistically, we showed that the HNF-1α transcriptionally activated STAT3, and subsequently increased the expressions of FGA and FGB. Additionally, suppression of HNF-1α improved the murine hypospadias via inactivating the STAT3. Therefore, our findings confirmed that HNF-1α promoted hypospadias and periurethral fibrosis by activating STAT3. Targeting HNF-1α might the future direction for hypospadias treatment.
研究领域:
医学
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分子生物学
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PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2022
·
IF 8.101
Jin Li,Zi-Hui Wang,Ya-Min Dang,Dan-Ni Li,Zhen Liu,Da-Peng Dai,Jian-Ping Cai
MTH1 protein can sanitize the damaged (d)NTP pool and MTH1 inhibitors have been developed to impede the growth of rapidly proliferating tumor cells; however, the effect of MTH1 inhibition on breast cancer stemness has not been reported yet. Here, we constructed breast cancer cell lines with the stable depletion of MTH1. MTH1 suppression clearly increased the ratio of CD44 + CD24 −/low subpopulations and promoted the formation of tumorspheres in MCF7 and T47D cells. RNA expression profiling, RT–qPCR and Western blotting showed the upregulation of master stem cell transcription factors Sox2 , Oct4 and Nanog in MTH1 knockdown cells. GSEA suggested and Western blotting verified that MTH1 knockdown increased the expression of phosphorylated STAT3 (Tyr705). Furthermore, we indirectly demonstrated that the increased concentration of 8-oxo-dGTP and 8-oxo-GTP in MTH1 -knockdown cells and exogenous 8-oxoGTP, rather than 8-oxo-dGTP, could significantly increase the phosphorylation of STAT3. In conclusion, this work indicates that MTH1 inhibition increased the proportion of breast cancer stem cells (BCSCs) and promoted stemness properties in MCF7 cells.
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
ACTA PHARMACOLOGICA SINICA
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2024
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IF 6.9
Zhang Chen-chun,Li Yuan,Jiang Chang-you,Le Qiu-min,Liu Xing,Ma Lan,Wang Fei-fei
The O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) is a critical post-translational modification that couples the external stimuli to intracellular signal transduction networks. However, the critical protein targets of O-GlcNAcylation in oxidative stress-induced apoptosis remain to be elucidated. Here, we show that treatment with H 2 O 2 inhibited O-GlcNAcylation, impaired cell viability, increased the cleaved caspase 3 and accelerated apoptosis of neuroblastoma N2a cells. The O-GlcNAc transferase (OGT) inhibitor OSMI-1 or the O-GlcNAcase (OGA) inhibitor Thiamet-G enhanced or inhibited H 2 O 2 -induced apoptosis, respectively. The total and phosphorylated protein levels, as well as the promoter activities of signal transducer and activator of transcription factor 3 (STAT3) and Forkhead box protein O 1 (FOXO1) were suppressed by OSMI-1. In contrast, overexpressing OGT or treating with Thiamet-G increased the total protein levels of STAT3 and FOXO1. Overexpression of STAT3 or FOXO1 abolished OSMI-1-induced apoptosis. Whereas the anti-apoptotic effect of OGT and Thiamet-G in H 2 O 2 -treated cells was abolished by either downregulating the expression or activity of endogenous STAT3 or FOXO1. These results suggest that STAT3 or FOXO1 are the potential targets of O-GlcNAcylation involved in the H 2 O 2 -induced apoptosis of N2a cells.
研究领域:
细胞生物学
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分子生物学
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神经科学
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PubMed
高影响因子
IMMUNOBIOLOGY
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2025
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IF 2.3
Yu-yao Qin,Zi-yi Qin,Tao Liang,Dong-er Qin,Sheng-yi Hua,Ming-hui Tan,Shun Guo,Fan Yang,Le Shi,Yun Yu,Guang-ji Zhang
Background Phellodendrine, a primary bioactive constituent of Phellodendron chinense Schneid (PCS), is crucial in its pharmacological profile. Phellodendrine exhibits potent anti-nephritic properties and demonstrates a marked inhibitory effect on the cellular immune response. However, the effects of phellodendrine on proteoglycan depletion and cartilage degeneration in gouty arthritis remain insufficiently understood. Therefore, the objective of this study is to elucidate the therapeutic potential and underlying mechanisms of phellodendrine chloride (PC) in the treatment of gouty arthritis. Methods A monosodium urate (MSU)-induced arthritis model in rats, along with a peritonitis model in mice, was developed, in combination with a chondrocyte model. Neutrophil proportions were quantified using flow cytometry. The expression levels of MMP-3, STAT3, and phosphorylated STAT3 (p-STAT3) in chondrocytes were determined by Western blot analysis. Proteoglycan levels in chondrocytes were assessed using toluidine blue staining and quantitative reverse transcription PCR (qRT-PCR). Joint swelling rates were monitored at 0–24 h in rats, and histopathological changes in joint tissues were subsequently analyzed. Results Phellodendrine chloride mitigated the rise in neutrophil proportions within MSU-induced peritoneal lavage fluid in mice and decreased inflammatory cell infiltration in rat ankle tissues. Treatment with phellodendrine chloride led to a downregulation of MMP-3 protein levels and inhibited IL-1β-induced proteoglycan degradation in chondrocytes. Additionally, results from experiments combining IL-1β with AG490 or IL-6 demonstrated that phellodendrine chloride attenuated IL-1β-induced MMP-3 expression and proteoglycan degradation. Conclusion Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway.
研究领域:
药理学
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免疫学
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风湿病学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Liangrong Wu,Chenchen Qian,Weiqi Zhang,Mengyun Shi,Xiuxiu Chen,Yi Wang,Feng Lin
Background Ginkgo biloba L., a kind of traditional Chinese medicine, is always used to treat various diseases. Ginkgetin is an active biflavonoid isolated from leaves of Ginkgo biloba L., which exhibits diverse biological activities, including anti-tumor, anti-microbial, anti-cardiovascular and cerebrovascular diseases, and anti-inflammatory effects. However, there are few reports on the effects of ginkgetin on ovarian cancer (OC). Hypothesis/Purpose OC is one of the most common cancers with high mortality in women. The purpose of this study was to find out how ginkgetin inhibited OC and which signal transduction pathways was involved to suppress OC. Methods The OC cell lines, A2780, SK-OV-3 and CP70, were used for in vitro experiments. MTT assay, colony formation, apoptosis assay, scratch wound assay and cell invasion assay were used to determine the inhibitory effect of ginkgetin. BALB/c nude female mice were injected with A2780 cells subcutaneously, then treated with ginkgetin by intragastric administration. Western blot experiment was used to verify the inhibitory mechanism of OC in vitro and in vivo . Results We found that ginkgetin inhibited the proliferation and induced apoptosis in OC cells. In addition, ginkgetin reduced migration and invasion of OC cells. In vivo study showed that ginkgetin significantly reduced tumor volume in the xenograft mouse model. Furthermore, the anti-tumor effects of ginkgetin were associated with a down regulation of p-STAT3, p-ERK and SIRT1 both in vitro and in vivo . Conclusion Our results suggest that ginkgetin exhibits anti-tumor activity in OC cells via inhibiting the JAK2/STAT3 and MAPK pathways and SIRT1 protein. Ginkgetin could be a potential candidate for the treatment of OC.
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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中药学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Chen Mingjun,Feng Yang,Luo Dan,Zhang Chen,Zhou Jing,Dai Hengheng,Lin Mingxiong,Tong ZhanQi
Purpose: Wuwei Kushen Changrong capsule (Composite Sophora Colon-soluble Capsule, CSCC) is a Chinese patent medicine developed to treat ulcerative colitis. Studies highlight CSCC potential efficacy for ulcerative colitis (UC) but unclear mechanism limits its widely treatment for patients. We aimed to investigate the anti-colitis efficacy of CSCC and explore the mechanism by which GPR43 inhibits the NLRP3/STAT3 signaling pathway, thereby mediating the protective effects of CSCC on the intestinal barrier.Methods: The protective effects of CSCC were evaluated in a murine ulcerative colitis model induced by 3% DSS. Assessments included body weight, Disease Activity Index (DAI) score, colon length, and histopathological score. Colon tissue, cell function, and immune-inflammatory status were evaluated using immunohistochemistry, immunofluorescence, ELISA, and real-time fluorescence quantitative PCR (RT-PCR). Protein expression levels of relevant pathways and receptors were measured using Western blot. All experiments were repeated.Results: CSCC protected mice from DSS-induced colitis by upregulating Gpr43, promoting the expression of ZO-1 and Occludin tight junction proteins. Mechanistically, CSCC inhibits the MEK4/JNK1/STAT3 activation pathway, consequently suppressing the STAT3/NLRP3/IL-1β pathway and inhibiting the production of inflammatory factors such as IL-17A.Conclusion: The mechanisms through which CSCC protects against DSS-induced colitis may include upregulating Gpr43, inhibiting the STAT3/NLRP3 pathway, and suppressing inflammation factors like IL-17A. These findings highlight the mechanisms underlying CSCC’s anti-colitis effects and suggest its potential as a therapeutic candidate for managing the progression of UC.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
Cancer Management and Research
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2019
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IF 2.243
Lehe Yang,Jifa Li,Lingyuan Xu,Shichong Lin,Youqun Xiang,Xuanxuan Dai,Guang Liang,Xiaoying Huang,Jiandong Zhu,Chengguang Zhao
Background Non-small-cell lung cancer (NSCLC) comprises about 85% of all lung cancers and is usually diagnosed at an advanced stage with poor prognosis. The IL-6/STAT3 signaling pathway plays a pivotal role in NSCLC biology. Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that Rhein has significant antitumor effects, supporting the potential uses of Rhein as an antitumor agent.Methods Cell viability and colony formation were performed to examine Rhein’s potent anti-proliferative effect in human NSCLC cell lines PC-9, H460 and A549. Flow cytometry-based assay was employed to study whether Rhein could affect cell apoptosis and cycle. The expression level of P-STAT3, apoptosis and cycle-related proteins Bcl-2, Bax, MDM2, CDC2, P53 and CyclinB1 were detected by Western blotting. The xenograft models were used to evaluate the in vivo effect of Rhein.Results We found that Rhein could significantly reduce the viability and stimulate apoptosis in human NSCLC cells in a dose-dependent manner. Western blot analysis results suggested that the antitumor effect of Rhein might be mediated via STAT3 inhibition. Rhein upregulated the expression of the proapoptotic protein Bax and downregulated the expression of the antiapoptotic protein Bcl-2. In addition, Rhein induced the arrest of NSCLC cells in the G2/M phase of the cell cycle and dose dependently inhibited the expression of cycle-related proteins. The Rhein also inhibited tumor growth in H460 xenograft models.Conclusion Rhein shows potent efficacy against NSCLC through inhibiting the STAT3 pathway. Our results also suggest that Rhein has a promising potential to be used as a novel antitumor agent for the treatment of NSCLC.
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
Iranian Journal of Basic Medical Sciences
·
2021
·
IF 2.699
Chuang Zhang,Suolin Li,Chi Sun,Lin Liu,Yanbin Fang,Xiaofeng Yang,Xingxin Pan,Ben Zhang
Objective(s): Vitexin, a natural flavonoid, is commonly found in many foods and traditional herbal medicines and has clear health benefits. However, the role of vitexin in cholestasis is presently unclear. This study investigated whether vitexin mitigated glycochenodeoxycholate (GCDC)-induced hepatocyte injury and further elucidated the underlying mechanisms. Materials and Methods: A cell counting kit-8 (CCK-8) assay was conducted to evaluate cell viability. The mitochondrial membrane potential (MMP, Δψm), reactive oxygen species (ROS) levels, and apoptosis rate of hepatocytes exposed to GCDC were detected by flow cytometry (FCM). We then measured the cytoprotective effects of vitexin against oxidative stress. The molecular signaling pathway was further investigated by using Western blotting and signaling pathway inhibitors. Results: Here, we showed that vitexin increased cell viability and reduced cell apoptosis, necroptosis, and oxidative stress in a dose-dependent manner in GCDC-treated hepatocytes. In addition, by using selective inhibitors, we further confirmed that inhibition of the JAK2/STAT3 pathway by vitexin was mediated by prolonged activation of Sirtuin 6 (SIRT6). Conclusion: Vitexin attenuated GCDC-induced hepatocyte injury via SIRT6 and the JAK2/STAT3 pathways.
研究领域:
药理学
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肝病学
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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
PHYTOTHERAPY RESEARCH
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2025
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IF 6.3
Qing Ning,Yingxue Yue,Xinlian Liu,Wenbo Ji,Qin Zhao,Jing Wang,Zhenhai Zhang
S afe and effective treatments for psoriasis are limited. Anisole is an active ingredient in citrus and basil volatile oils; however, its potential for psoriasis treatment remains unexplored. To investigate the effects and mechanism of anisole transdermal administration as a treatment for psoriasis. Imiquimod (IMQ) was used to establish a C57 mouse psoriasis model. The severity of psoriasis lesions in each group was assessed by evaluating the thickness of skin lesions, erythema, and scales. Pathological changes within the epidermis organization were evaluated via hematoxylin and eosin (H&E) staining using light microscopy. Serum inflammatory factor levels were measured by enzyme-linked immunosorbent assays. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were performed to analyze the mRNA levels of relevant inflammatory factors and the expression of key proteins at the skin lesion sites in psoriatic mice. In model mice, applying anisole hydrogels significantly reduced the serum levels of pro-inflammatory factors interleukin (IL)-17A, (IL)-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. H&E staining revealed significantly attenuated stratum spinosum thickening and lymphocyte infiltration in the treatment group. RT-qPCR results further demonstrated that the skin tissues from the treatment group exhibited significantly reduced Il1b , Il17a , Il22 , and Tnfa mRNA expression. Western blotting revealed inhibition of the JAK1/STAT3 signaling pathway within anisole-treated psoriatic tissues. Anisole potentially reduces psoriatic-associated inflammation through the JAK1/STAT3 signaling pathway, alleviating IMQ-induced psoriasis.
研究领域:
皮肤病学
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免疫学
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药理学
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DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
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2020
·Vol. 42
·期 10
·2049-2058
·
IF 1.977
Song Lingyu,Wang Yan,Zhen Yunhuan,Li Dengke,He Xidong,Yang Hong,Zhang Huayang,Liu Qi
Cancer metastasis is the primary cause of death in patients diagnosed with colorectal cancer. Piperine, an active nontoxic ingredient in pepper, has potent anti-inflammatory and anti-cancer properties. However, little is known about the anti-migratory and anti-invasive effects of piperine on colorectal cancer. We demonstrated piperine inhibited the migration and invasion of colorectal cancer cells. Then, we found piperine reversed the biomarker expression of epithelial-to-mesenchymal transition (EMT), and suppressed the EMT regulator Snail. Furthermore, signal transducers and activators of transcription 3 (STAT3) was downregulated by piperine. Finally, STAT3 inhibitors were applied to observe the role of STAT3 in colorectal cancer migration, invasion and EMT. Collectively, piperine inhibits colorectal cancer migratory and invasive capacities through STAT3/Snail mediated EMT. Therefore, piperine could be applied as a possible therapeutic regimen for the prevention of colorectal cancer metastasis.
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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产品关联
DOI
PubMed
高影响因子
American Journal of Cancer Research
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2024
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IF 3.6
Xiao-Li Zheng,Zhi-Di Li,Kai-Zhi Luo,Yang-Ling Li,Ye-Han Liu,Shu-Ying Shen,Fei-Yan Shen,Wan-Yan Li,Guo-Qing Chen,Chong Zhang,Ling-Hui Zeng
Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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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）