المؤلفون: Kai Yue, Yansheng Wu, Beibei Ye, Peng Chen, Qingchuan Lai, Xudong Wang, Chao Jing, Yue Wu, Mengqian Zhou, Yuansheng Duan, Xingchen Li, Xiaofeng Yao, Dandan Liu, Hong Li, Linqi Li, Shengchi Zhang

المصدر: Theranostics

مصطلحات موضوعية: Male, 0301 basic medicine, Esophageal Neoplasms, Carcinogenesis, Medicine (miscellaneous), Snail, medicine.disease_cause, Metastasis, Mice, 0302 clinical medicine, Cell Movement, PSMD14, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, biology, SNAIL, EMT, Esophageal cancer, Pyrrolidinones, Up-Regulation, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Chemosensitivity, Research Paper, medicine.drug, Proteasome Endopeptidase Complex, Epithelial-Mesenchymal Transition, Mice, Nude, Antineoplastic Agents, 03 medical and health sciences, Downregulation and upregulation, Esophageal squamous cell carcinoma, In vivo, Cell Line, Tumor, biology.animal, Biomarkers, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, Cell Proliferation, Cisplatin, business.industry, Ubiquitination, medicine.disease, Thiolutin, 030104 developmental biology, Trans-Activators, Cancer research, Snail Family Transcription Factors, business

الوصف: Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC. Methods: Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using in vitro and in vivo experiments. Immunoprecipitation and in vivo ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14. Results: Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of in vitro and in vivo assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer. Conclusion: Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c47c33d3831d41492d14a4c177dc6b7Test
https://doi.org/10.7150/thno.46109Test

المؤلفون: Xudong Wang, Mengqian Zhou, Wenchao Zhang, Hui Wei, Xiaofeng Yao, Beibei Ye, Chao Jing, Yuansheng Duan, Xingchen Li, Shanshan Zhuo, Kai Yue, Yansheng Wu, Dandan Liu, Linqi Li, Qingchuan Lai

المصدر: Theranostics

مصطلحات موضوعية: 0301 basic medicine, Carcinogenesis, Medicine (miscellaneous), medicine.disease_cause, Deubiquitinating enzyme, Mice, 0302 clinical medicine, PSMD14, E2F1, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, Deubiquitinating Enzymes, Prognosis, Pyrrolidinones, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Chemoresistance, medicine.drug, Research Paper, Proteasome Endopeptidase Complex, Mice, Nude, Biology, 03 medical and health sciences, stomatognathic system, Cell Line, Tumor, medicine, otorhinolaryngologic diseases, Animals, Humans, Protein kinase B, neoplasms, PI3K/AKT/mTOR pathway, Cell Proliferation, Squamous Cell Carcinoma of Head and Neck, SOXB1 Transcription Factors, Ubiquitination, Head and neck squamous cell carcinoma, medicine.disease, Thiolutin, Head and neck squamous-cell carcinoma, stomatognathic diseases, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, biology.protein, Trans-Activators, Chromatin immunoprecipitation, Proto-Oncogene Proteins c-akt, E2F1 Transcription Factor

الوصف: Increasing evidence reveals a close relationship between deubiquitinating enzymes (DUBs) and cancer progression. In this study, we attempted to identify the roles and mechanisms of critical DUBs in head and neck squamous cell carcinoma (HNSCC). Methods: Bioinformatics analysis was performed to screen differentially expressed novel DUBs in HNSCC. Immunohistochemistry assay was used to measure the expression of DUB PSMD14 in HNSCC specimens and adjacent normal tissues. The level of PSMD14 in HNSCC tumorigenesis was investigated using a 4-NQO-induced murine HNSCC model. The function of PSMD14 was determined through loss-of-function assays. Chromatin immunoprecipitation, immunoprecipitation and in vivo ubiquitination assay were conducted to explore the potential mechanism of PSMD14. The anti-tumor activity of PSMD14 inhibitor Thiolutin was assessed by in vitro and in vivo experiments. Results: We identified PSMD14 as one of significantly upregulated DUBs in HNSCC tissues. Aberrant expression of PSMD14 was associated with tumorigenesis and malignant progression of HNSCC and further indicated poor prognosis. The results of in vitro and in vivo experiments demonstrated PSMD14 depletion significantly undermined HNSCC growth, chemoresistance and stemness. Mechanically, PSMD14 inhibited the ubiquitination and degradation of E2F1 to improve the activation of Akt pathway and the transcription of SOX2. Furthermore, PSMD14 inhibitor Thiolutin exhibited a potent anti-tumor effect on HNSCC in vivo and in vitro by impairing DUB activity of PSMD14. Conclusion: Our findings demonstrate the role and mechanism of PSMD14 in HNSCC, and provide a novel and promising target for diagnosis and clinical therapy of HNSCC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41457b31fc40f3f3f83e381a98fab731Test
http://europepmc.org/articles/PMC7806466Test

المؤلفون: Yu Shuang, Xiaofeng Yao, Jing Liu, Juntao Niu, Wenyu Guo, Chao Li

المصدر: Human cell. 35(4)

مصطلحات موضوعية: Cancer Research, Carcinogenesis, Squamous Cell Carcinoma of Head and Neck, Cell Biology, Gene Expression Regulation, Neoplastic, Extracellular Vesicles, MicroRNAs, Head and Neck Neoplasms, Cell Line, Tumor, Carcinoma, Squamous Cell, Humans, Laryngeal Neoplasms, Cell Proliferation, Smad4 Protein

الوصف: Serum-derived extracellular vesicles (EVs) containing non-coding RNAs have been indicated to serve as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC), while their functional role remains to be explored. Here, we summarize the possible mechanism explaining the laryngeal carcinogenesis and the associated changes with the involvement of extracellular microRNA (miR)-27a from serum of LSCC patients. Serum-derived EVs from LSCC patients were found to increase the proliferative activity and decreased the apoptotic activity of LSCC cells. miRNA microarrays revealed that miR-27a expression was elevated after EV treatment. miR-27a expression was elevated in LSCC tissues and predicted a poor prognosis for patients. Downregulation of miR-27a inhibited the effect of EVs to reduce the activity of LSCC cells in vitro and to suppress tumor development in vivo. miR-27a targeted SMAD family member 4 (Smad4) to mediate the Wnt/β-catenin pathway, which was induced under the influence of EVs. Smad4 was downregulated in LSCC tissues, and simultaneous overexpression of miR-27a and Smad4 resulted in reduced cell activity and tumorigenicity. In conclusion, serum-derived EVs support the laryngeal carcinogenesis at least partially via transferring miR-27a. miR-27a targets Smad4 and is a biomarker to predict LSCC prognosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f34c381784aa042a36d7987b03754855Test
https://pubmed.ncbi.nlm.nih.gov/35545731Test

المؤلفون: Rui Jin, Xuan Zhou, Xiaofeng Yao, Qiang Zhang, Ping Li, Chao Jing, Yu Wang, Wenchao Zhang, Yuansheng Duan, Xudong Wang, Yingjie Tao

المصدر: Cancer Letters. 432:38-46

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Adenoid cystic carcinoma, Perineural invasion, Mice, Nude, Motility, Apoptosis, medicine.disease_cause, Metastasis, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Tumor Cells, Cultured, medicine, Animals, Humans, Cell Proliferation, Mice, Inbred BALB C, Mutation, business.industry, Liver Neoplasms, NF-kappa B, Zinc Finger E-box-Binding Homeobox 1, NF-κB, Prognosis, Salivary Gland Neoplasms, medicine.disease, Carcinoma, Adenoid Cystic, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Survival Rate, Insulin-Like Growth Factor Binding Protein 2, 030104 developmental biology, Oncology, chemistry, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, business, Nuclear localization sequence, Signal Transduction

الوصف: Metastasis is a major cause of poor prognosis in patients suffered with salivary adenoid cystic carcinoma (SACC), in which many factors are implicated. In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF-κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC. In addition, IGFBP2 mutation in the nuclear localization signal could impede nuclear translocation of p65, lower ZEB1 expression, and abrogate the EMT process. In xenograft models, IGFBP2 overexpression promoted lung and liver metastases of SACC cells; while if nuclear IGFBP2 was reduced, the formation of metastases in lung and liver was weakened. Together, these results for the first time demonstrate that IGFBP2 plays an important role in invasion and metastasis of SACC through the NF-κB/ZEB1 signaling pathway and IGFBP2 may be a novel biomarker and target for SACC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d4ac1ce9543ace508a445463d56d618Test
https://doi.org/10.1016/j.canlet.2018.06.008Test

المؤلفون: Chengyan Geng, Qiujuan Li, Xiaofeng Yao, Liping Jiang, Zeyun Gao, Yong Liu, Xiaoxia Shi, Xuan Wang, Jun Cao, Zhiguo Li

المصدر: Toxicology in vitro : an international journal published in association with BIBRA. 66

مصطلحات موضوعية: 0301 basic medicine, Cell Survival, ATG5, Autophagy-Related Proteins, Toxicology, Autophagy-Related Protein 5, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Adenosine Triphosphate, Autophagy, Humans, Glycolysis, Lactic Acid, Cell Proliferation, A549 cell, Chemistry, Cell growth, Cell Cycle, General Medicine, Transfection, Cell cycle, Cell biology, Cysteine Endopeptidases, 030104 developmental biology, Glucose, Anaerobic glycolysis, 030220 oncology & carcinogenesis, Cadmium

الوصف: Cadmium (Cd) is a pervasive harmful metal in the environment. It is a well-known inducer of tumorigenesis, but its mechanism is still unclear. We have previously reported that Cd-induced autophagy was apoptosis-dependent and prevents apoptotic cell death to ensure the growth of A549 cells. In this study, the mechanism was further investigated. Cd treatment increased glucose uptake and lactate release significantly. Meanwhile, the protein level of GLUT1，HKII，PKM2 and LDHA increased in a time-dependent manner, indicating that Cd induced aerobic glycolysis in A549 and HELF cells. The inhibitors of autophagy, 3MA, and CQ, repressed Cd-induced glycolysis-related proteins, indicating that autophagy was involved in Cd-induced glycolysis in A549 and HELF cells. Knockdown of ATG4B or ATG5 by siATG4B and siATG5 decreased Cd-induced glycolysis, while overexpression of ATG4B enhanced glycolysis. These results demonstrated that Cd-induced glycolysis was autophagy-dependent. Then, glycolysis inhibitor, 2DG and siPKM2 could inhibit Cd-induced cell viability and cell cycle progression compared to only Cd treatment, indicating that glycolysis played an important role in Cd-induced cell growth. Finally, co-treatment of transfection of ATG4B-DNA plasmids with 2DG or siPKM2 further demonstrated that the autophagy-glycolysis axis played an important role in Cd-induced cell cycle progression. Taken together, our results suggested that Cd-induced glycolysis is autophagy-dependent and the autophagy-glycolysis axis underlies the mechanism of Cd-induced cell growth in A549 and HELF cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbbf1aea4bde2a61bb0478037340cedbTest
https://pubmed.ncbi.nlm.nih.gov/32200033Test

المؤلفون: Yu Qiao, Jingxuan Yang, Shanshan Sun, Chuanqiang Wu, Yu Wang, Minghui Zhao, Xudong Wang, Xuan Zhou, Mingyang Liu, Min Li, Feng Yu, Lun Zhang, Zhaoqing Li, Chao Zhang, Yu Ren, Lingping Kong, Yuqing Zhang, Chao Jing, Xiaofeng Yao, Yansheng Wu, Wenyu Guo

المصدر: Clinical Cancer Research. 24:2665-2677

مصطلحات موضوعية: STAT3 Transcription Factor, 0301 basic medicine, Cancer Research, Antineoplastic Agents, Mice, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Cell Line, Tumor, otorhinolaryngologic diseases, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, RNA, Small Interfering, STAT3, neoplasms, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Cisplatin, Cetuximab, biology, Squamous Cell Carcinoma of Head and Neck, Chemistry, Cell Cycle, EZH2, HOTAIR, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Disease Models, Animal, stomatognathic diseases, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, biology.protein, RNA Interference, RNA, Long Noncoding, HOX Transcript Antisense RNA, Signal Transduction, medicine.drug

الوصف: Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy. Experimental Design: We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation in vitro and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by in vitro assays. Results: HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors in vivo. Conclusions: Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC. Clin Cancer Res; 24(11); 2665–77. ©2018 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89eb7b49550e79381c323aa3511cf71fTest
https://doi.org/10.1158/1078-0432.ccr-16-2248Test

المؤلفون: Liping Jiang, Xiaona Yan, Linlin Sui, Chengyan Geng, Xiaofeng Yao, Ying Kong, Jun Cao, Huaying Xie, Wei Lv, Qiujuan Li

المصدر: Chemico-biological interactions. 279

مصطلحات موضوعية: 0301 basic medicine, Autophagosome, Autophagy-Related Proteins, Adenocarcinoma, Toxicology, 03 medical and health sciences, Downregulation and upregulation, Western blot, Cell Movement, Cell Line, Tumor, medicine, Autophagy, Humans, Neoplasm Invasiveness, Cell Proliferation, A549 cell, chemistry.chemical_classification, Matrigel, Reactive oxygen species, medicine.diagnostic_test, Chemistry, Cell growth, General Medicine, Cell biology, Up-Regulation, Gene Expression Regulation, Neoplastic, Cysteine Endopeptidases, 030104 developmental biology, Reactive Oxygen Species, Cadmium

الوصف: Cadmium (Cd) is a toxic heavy metal that is widely used in industry and agriculture. In this study the role of autophagy in Cd-induced proliferation, migration and invasion was investigated in A549 cells. Exposure to Cd (2 μM) significantly increased reactive oxygen species (ROS) production, induced autophagy and enhanced cell growth, migration and invasion in A549 cells. Western blot analysis showed that the expression of autophagy-related proteins, LC3-II, Beclin-1 and Atg4 and invasion-related protein MMP-9 were upregulated in Cd-treated cells. N-acetyl cysteine (NAC) markedly prevented Cd-induced proliferation of A549 cells and the increasing protein level of LC3-II and Atg4. Blocking Atg4 expression by siRNA strongly reduced Beclin-1 and LC3-II protein expression and the number of autophagosome positive cells induced by Cd. Furthermore, Atg4 siRNA increased the number of cells at G0/G1 phase, reduced the number of S and G2/M phase cells, and inhibited Cd-induced cell growth significantly compared with that of Cd-treated Control siRNA cells. 3-MA pretreatment increased the percentage of G0/G1 phase cells, decreased S phase and G2/M phase percentage, and inhibited Cd-induced cell growth remarkably compared with that of only Cd-treated cells. Knocking down Atg4 reduced the number of cells that migrated and invaded through the Matrigel matrix significantly and led to a significant decrease of MMP-9 expression. In addition, in lung tissues of Cd-treated BALB/c mice, the increased expression of LC3-II, Beclin-1 and Atg4 were observed. Taken together, our results demonstrated that ROS-dependent Atg4-mediated autophagy plays an important role in Cd-induced cell growth, migration and invasion in A549 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a641bce1ba7be39672e0841ba1d38b8Test
https://pubmed.ncbi.nlm.nih.gov/29179951Test

المؤلفون: Zhaoqing Li, Sinan Wang, Na Ye, Jiabin Dong, Xuan Zhou, Minghui Zhao, Yansheng Wu, Yu Wang, Xudong Wang, Yu Ren, Xin Qu, Qiang Shen, Linhgping Kong, Kailiang Zhang, Yu Qiao, Chao Zhang, Shanshan Sun, Xiaofeng Yao, Wenyu Guo, Rui Jin, Lun Zhang, Haiying Chen, Chao Jing, Jia Zhou

مصطلحات موضوعية: 0301 basic medicine, STAT3 Transcription Factor, Cancer Research, medicine.medical_specialty, Beta-catenin, Cell Survival, Cell, Antineoplastic Agents, Salicylanilides, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, STAT3, beta Catenin, Cell Proliferation, biology, Cell growth, Squamous Cell Carcinoma of Head and Neck, Cell cycle, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Oncology, Apoptosis, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Catenin, Cancer research, biology.protein, Carcinoma, Squamous Cell, Niclosamide, Signal transduction, Signal Transduction

الوصف: Signal transducer and activator of transcription 3 (STAT3) is involved in the tumor growth and metastasis of human head and neck squamous cell carcinoma (HNSCC) and is therefore a target with therapeutic potential. In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both in vitro and in vivo via inactivating STAT3 and downstream miR-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0–G1 phase, induced apoptosis, and reduced cell invasion in both SCC25 and CAL27 cell lines. Moreover, HJC0152 inhibited nuclear translocation of phosphorylated STAT3 at Tyr705 and decreased VHL/β-catenin signaling activity via regulation of miR-21. Loss of function of VHL remarkably compromised the antitumor effect of HJC0152 in both cell lines. In our SCC25-derived orthotopic mouse models, HJC0152 treatment significantly abrogated STAT3/β-catenin expression in vivo, leading to a global decrease of tumor growth and invasion. With its favorable aqueous solubility and oral bioavailability, HJC0152 holds the potential to be translated into the clinic as a promising therapeutic strategy for patients with HNSCC. Mol Cancer Ther; 16(4); 578–90. ©2017 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce55a0ac3093153620dc592d3f16ec7fTest
https://europepmc.org/articles/PMC5380531Test/