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Huang Z, Liao Y, Zheng Y, Ye S, Zhang Q, Yu X, Liu X, Li N. Zinc Deficiency Causes Glomerulosclerosis and Renal Interstitial Fibrosis Through Oxidative Stress and Increased Lactate Metabolism in Rats. Biol Trace Elem Res 2025; 203:2084-2098. [PMID: 39028478 PMCID: PMC11919932 DOI: 10.1007/s12011-024-04306-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 07/07/2024] [Indexed: 07/20/2024]
Abstract
Chronic kidney disease (CKD) is a highly prevalent condition characterized by renal fibrosis as its ultimate manifestation. Zinc deficiency is closely associated with CKD, evidenced by its link to renal fibrosis. Recently, local lactic acidosis has been demonstrated to promote renal fibrosis. Under zinc-deficient conditions, mitochondrial function is compromised and abnormal lactate metabolism might be induced potentially. However, it remains unclear whether zinc deficiency leads to renal fibrosis through local lactic acidosis. Zinc deficiency rat models were successfully established by feeding zinc-deficient diet. Western blot, qPCR, IHC, and other experiments were employed to investigate the key markers and molecular mechanisms of glomerulosclerosis and renal interstitial fibrosis. Our results indicate that zinc deficiency reduces specific markers of podocytes (podocalyxin, WT1, and nephrin) and activates the Wnt3a/β-catenin pathway, a key pathway in podocyte injury. Concurrently, glomerulosclerosis is indicated by increased urinary microalbumin and serum creatinine levels along with histological alteration observed through PAS and Masson staining in zinc-deficient rats. Furthermore, various degrees of upregulation for several markers of interstitial fibrosis including α-SMA, FN1 and collagen III are also revealed. These findings were further confirmed by Masson staining and IHC. Additionally, alterations in four markers in the EMT process, N-cadherin, E-cadherin, Vimentin, and snail, were consistent with expectations. We then confirmed the activation of the non-canonical TGF-β1 pathway known as the PI3K/AKT/mTOR pathway. An elevation in renal ROS levels accompanied by increased mitochondrial marker cytochrome C expression as well as an elevated NADH/NAD + ratio is also observed within the kidneys. Furthermore, the activity of both MMP/TIMP system and fibrinolytic system was abnormally enhanced under zinc deficiency conditions. Finally, we find zinc supplementation could significantly ameliorate relevant pathological alterations induced by zinc deficiency. These results collectively point that zinc deficiency causes podocyte damage ultimately resulting in glomerulosclerosis via accumulation of ROS and induces interstitial fibrosis via lactic acidosis.
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Affiliation(s)
- Zixuan Huang
- Department of Nephrology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Queen Mary University of London, London, E1 4NS, UK
| | - Yajie Liao
- Queen Mary University of London, London, E1 4NS, UK
| | - Yunxi Zheng
- Queen Mary University of London, London, E1 4NS, UK
| | - Shang Ye
- Queen Mary University of London, London, E1 4NS, UK
| | - Qianyu Zhang
- Queen Mary University of London, London, E1 4NS, UK
| | - Xiaohong Yu
- Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
| | - Xiaoxin Liu
- Department of Nephrology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Ningxu Li
- Department of Nephrology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Wang Y, Ding L, Feng J, Lin Z, Yao H, You X, Zhang X, Sun W, Liu Y, Wang P. Mesoporous cerium oxide nanoenzyme for Efficacious impeding tumor and metastasis via Conferring resistance to anoikis. Biomaterials 2025; 314:122876. [PMID: 39383776 DOI: 10.1016/j.biomaterials.2024.122876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/20/2024] [Accepted: 10/03/2024] [Indexed: 10/11/2024]
Abstract
Tumor cells can survive when detached from the extracellular matrix or lose cell-to-cell connections, leading to a phenomenon known as anoikis resistance (AR). AR is closely associated with the metastasis and proliferation of tumor cells, enabling them to disseminate, migrate, and invade after detachment. Here, we have investigated a novel composite nanoenzyme comprising mesoporous silica/nano-cerium oxide (MSN-Ce@SP/PEG). This nanoenzyme exhibited satisfactory catalase (CAT) activity, efficiently converting high levels of H2O2 within tumor cells into O2, effectively alleviating tumor hypoxia. Furthermore, MSN-Ce@SP/PEG nanoenzyme demonstrated high peroxidase (POD) activity, elevating reactive oxygen species (ROS) levels and attenuating AR in hepatocellular carcinoma (HCC) cells. The MSN-Ce@SP/PEG nanoenzyme exhibited satisfactory dual bioactivity in CAT and POD and was significantly enhanced under favorable photothermal conditions. Through the synergistic effects of these capabilities, the nanoenzyme disrupted the epithelial-mesenchymal transition (EMT) process in detached HCC cells, ultimately inhibiting the recurrence and metastasis potential of anoikis-resistant HCC cells. This study represents the first report of a novel nanoenzyme based on mesoporous silica/nano-cerium oxide for treating AR in HCC cells, thereby suppressing HCC recurrence and metastasis. The findings of this work offer a pioneering perspective for the development of innovative strategies to prevent the recurrence and metastasis of HCC.
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Affiliation(s)
- Yunhao Wang
- Zhongnan Hospital of Wuhan University, Wuhan, Hubei, PR China
| | - Lei Ding
- Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, PR China; School of Rare Earths, University of Science and Technology of China, Hefei, 230026, PR China
| | - Juan Feng
- Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, 361003, PR China
| | - Ziguo Lin
- Zhongnan Hospital of Wuhan University, Wuhan, Hubei, PR China
| | - Hanlin Yao
- Zhongnan Hospital of Wuhan University, Wuhan, Hubei, PR China
| | - Xinyu You
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei, PR China
| | - Xiaolong Zhang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
| | - Wen Sun
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, PR China.
| | - Yang Liu
- Zhongnan Hospital of Wuhan University, Wuhan, Hubei, PR China.
| | - Peiyuan Wang
- Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, PR China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China.
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Zhao B, Ye DM, Li S, Zhang Y, Zheng Y, Kang J, Wang L, Zhao N, Ahmad B, Sun J, Yu T, Wu H. FMNL3 Promotes Migration and Invasion of Breast Cancer Cells via Inhibiting Rad23B-Induced Ubiquitination of Twist1. J Cell Physiol 2025; 240:e31481. [PMID: 39582466 DOI: 10.1002/jcp.31481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 10/18/2024] [Accepted: 10/24/2024] [Indexed: 11/26/2024]
Abstract
Breast cancer is a heterogeneous malignant tumor, and its high metastasis rate depends on the abnormal activation of cell dynamics. Formin-like protein 3 (FMNL3) plays an important role in the formation of various cytoskeletons that participate in cell movement. The objective of this study was to explore the function of FMNL3 in breast cancer progression and endeavor to reveal the molecular mechanism of this phenomenon. We found that FMNL3 was abnormally highly expressed in aggressive breast cancer cells and tissues, and it significantly inhibited E-cadherin expression. FMNL3 could specifically interact with Twist1 rather than other epithelial-mesenchymal transition transcription factors (EMT-TFs). We also found that FMNL3 enhanced the repressive effect of Twist1 on CDH1 transcription in breast cancer cells. Further mechanism studies showed that FMNL3 suppressed the ubiquitin degradation of Twist1 by inhibiting the interaction between Twist1 and Rad23B, the ubiquitin transfer protein of Twist1. In vitro functional experiments, it was confirmed that FMNL3 promoted the migration and invasion of breast cancer cells by regulating Twist1. Furthermore, Twist1 could directly bind to the fmnl3 promoter to facilitate FMNL3 transcription. To conclude, this study indicated that FMNL3 acted as a pro-metastasis factor in breast cancer by promoting Twist1 stability to suppress CDH1 transcription.
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Affiliation(s)
- Binggong Zhao
- School of Bioengineering and Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning, China
| | - Dong-Man Ye
- Department of Medical Imaging, Cancer Hospital of Dalian University of Technology, Shenyang, Liaoning, China
| | - Shujing Li
- School of Bioengineering and Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning, China
| | - Yong Zhang
- Department of Medical Imaging, Cancer Hospital of Dalian University of Technology, Shenyang, Liaoning, China
| | - Yang Zheng
- Department of Medical Imaging, Cancer Hospital of Dalian University of Technology, Shenyang, Liaoning, China
| | - Jie Kang
- School of Bioengineering and Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning, China
| | - Luhong Wang
- School of Bioengineering and Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning, China
| | - Nannan Zhao
- Department of Medical Imaging, Cancer Hospital of Dalian University of Technology, Shenyang, Liaoning, China
| | - Bashir Ahmad
- School of Bioengineering and Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning, China
| | - Jing Sun
- Department of Medical Imaging, Cancer Hospital of Dalian University of Technology, Shenyang, Liaoning, China
| | - Tao Yu
- Department of Medical Imaging, Cancer Hospital of Dalian University of Technology, Shenyang, Liaoning, China
| | - Huijian Wu
- School of Bioengineering and Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning, China
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Chen T, Karedla N, Enderlein J. Observation of E-cadherin adherens junction dynamics with metal-induced energy transfer imaging and spectroscopy. Commun Biol 2024; 7:1596. [PMID: 39613901 DOI: 10.1038/s42003-024-07281-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 11/15/2024] [Indexed: 12/01/2024] Open
Abstract
Epithelial cadherin (E-cad) mediated cell-cell junctions play a crucial role in the establishment and maintenance of tissues and organs. In this study, we employed metal-induced energy transfer imaging and spectroscopy to investigate variations in intermembrane distance during adhesion between two model membranes adorned with E-cad. By correlating the measured intermembrane distances with the distinct E-cad junction states, we probed the dynamic behavior and diversity of E-cad junctions across different binding pathways. Our observations led to the identification of a transient intermediate state referred to as the X-dimeric state and enabled a detailed analysis of its kinetics. We discovered that the formation of the X-dimer leads to significant membrane displacement, subsequently impacting the formation of other X-dimers. These direct experimental insights into the subtle dynamics of E-cad-modified membranes and the resultant changes in intermembrane distance provide perspectives on the assembly of E-cad junctions between cells. This knowledge enhances our comprehension of tissue and organ development and may serve as a foundation for the development of innovative therapeutic strategies for diseases linked to cell-cell adhesion abnormalities.
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Affiliation(s)
- Tao Chen
- Third Institute of Physics-Biophysics, Georg August University, Göttingen, Germany.
| | - Narain Karedla
- The Rosalind Franklin Institute, Didcot, UK
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
| | - Jörg Enderlein
- Third Institute of Physics-Biophysics, Georg August University, Göttingen, Germany.
- Cluster of Excellence 'Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells' (MBExC), Universitätsmedizin Göttingen, Göttingen, Germany.
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Karetnikova ES, Livanova AA, Fedorova AA, Markov AG. Early Radiation-Induced Changes in Lung Tissue and Intercellular Junctions: Implications for Tissue Repair and Fibrosis. PATHOPHYSIOLOGY 2024; 31:531-544. [PMID: 39449521 PMCID: PMC11503413 DOI: 10.3390/pathophysiology31040039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 09/13/2024] [Accepted: 09/21/2024] [Indexed: 10/26/2024] Open
Abstract
Early changes in lung tissue following ionizing radiation (IR) initiate processes that may lead to either regeneration or fibrosis. Intercellular junction proteins play a crucial role in the organization and function of epithelial tissues, both under normal conditions and after injuries. Alterations in the expression and localization of these proteins can influence the fate of epithelial cells. This study aims to investigate the effects of IR on lung tissue structure, as well as on the levels and distribution of intercellular junction proteins. Wistar rats were subjected to total X-ray irradiation at doses of 2 and 10 Gy. Lung tissue samples were collected for Western blot and histological analysis 72 h post-IR. IR at doses of 2 and 10 Gy led to structural changes in lung tissue and elevated levels of E-cadherin. The 10 Gy IR resulted in increased claudin-4 and occludin in lung parenchyma, decreased claudin-8 and claudin-12 in bronchial epithelium and endothelium, and suppression of apoptosis. Data evaluation indicated that alterations in the protein composition of intercellular junctions are essential processes in lung tissue at early stages after IR, and at least some of these alterations are associated with adaptation.
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Affiliation(s)
- Ekaterina S. Karetnikova
- Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia
- Interoception Laboratory, Pavlov Institute of Physiology RAS, 199034 St. Petersburg, Russia
| | - Alexandra A. Livanova
- Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia
| | - Arina A. Fedorova
- Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia
| | - Alexander G. Markov
- Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia
- Interoception Laboratory, Pavlov Institute of Physiology RAS, 199034 St. Petersburg, Russia
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Jiwa H, Xie Z, Qu X, Xu J, Huang Y, Huang X, Zhang J, Wang N, Li N, Luo J, Luo X. Casticin induces ferroptosis in human osteosarcoma cells through Fe 2+ overload and ROS production mediated by HMOX1 and LC3-NCOA4. Biochem Pharmacol 2024; 226:116346. [PMID: 38852641 DOI: 10.1016/j.bcp.2024.116346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 05/18/2024] [Accepted: 06/06/2024] [Indexed: 06/11/2024]
Abstract
Osteosarcoma is a primary solid bone malignancy, and surgery + chemotherapy is the most commonly used treatment. However, chemotherapeutic drugs can cause a range of side effects. Casticin, a polymethoxyflavonoid, has anti-tumor therapeutic effects. This study is aim to investigate the anti-osteosarcoma activity of casticin and explore the mechanism. Crystal violet staining, MTT assay, colony formation assay, wound healing assay, transwell assay, hoechst 33,258 staining, and flow cytometry analysis were used to investigate the effects of casticin on proliferation, migration, invasion, and apoptosis of osteosarcoma cells in vitro. The intracellular Fe2+, ROS, MDA, GSH/GSSG content changes were detected using the corresponding assay kits. The mRNA sequencing + bioinformatics analysis and western blot were used to detect the possible mechanism. We found that casticin caused G2/M phase cell cycle arrest in human osteosarcoma cells, inhibited the migration and invasion, and induced cell apoptosis and ferroptosis. Mechanistic studies showed the ferroptosis pathway was enriched stronger than apoptosis. Casticin up-regulated the expression of HMOX1, LC3 and NCOA4, meanwhile it activated MAPK signaling pathways. Animal experiments proved that casticin also inhibited the growth and metastasis of osteosarcoma cell xenograft tumor in vivo. In conclusion, casticin can induce ferroptosis in osteosarcoma cells through Fe2+ overload and ROS production mediated by HMOX1 and LC3-NCOA4. This provides a new strategy for osteosarcoma treatment.
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Affiliation(s)
- Habu Jiwa
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Zhou Xie
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Xiao Qu
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jingtao Xu
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yanran Huang
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Xiongjie Huang
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jun Zhang
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Nan Wang
- Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ningdao Li
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
| | - Jinyong Luo
- Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
| | - Xiaoji Luo
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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Chen H, Wang S, Cao Y, Lei H. Molecular Force Sensors for Biological Application. Int J Mol Sci 2024; 25:6198. [PMID: 38892386 PMCID: PMC11173168 DOI: 10.3390/ijms25116198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/29/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
The mechanical forces exerted by cells on their surrounding microenvironment are known as cellular traction forces. These forces play crucial roles in various biological processes, such as tissue development, wound healing and cell functions. However, it is hard for traditional techniques to measure cellular traction forces accurately because their magnitude (from pN to nN) and the length scales over which they occur (from nm to μm) are extremely small. In order to fully understand mechanotransduction, highly sensitive tools for measuring cellular forces are needed. Current powerful techniques for measuring traction forces include traction force microscopy (TFM) and fluorescent molecular force sensors (FMFS). In this review, we elucidate the force imaging principles of TFM and FMFS. Then we highlight the application of FMFS in a variety of biological processes and offer our perspectives and insights into the potential applications of FMFS.
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Affiliation(s)
- Huiyan Chen
- National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, China; (H.C.); (S.W.)
| | - Shouhan Wang
- National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, China; (H.C.); (S.W.)
| | - Yi Cao
- National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, China; (H.C.); (S.W.)
| | - Hai Lei
- School of Physics, Zhejiang University, Hangzhou 310027, China
- Institute for Advanced Study in Physics, Zhejiang University, Hangzhou 310027, China
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8
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Liu C, Wang J, Tan Y, Liu C, Qu X, Liu H, Tan M, Deng C, Qin X, Xiang Y. CTNNAL1 promotes the structural integrity of bronchial epithelial cells through the RhoA/ROCK1 pathway. Acta Biochim Biophys Sin (Shanghai) 2024; 56:753-762. [PMID: 38602002 PMCID: PMC11177105 DOI: 10.3724/abbs.2024026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 01/04/2024] [Indexed: 04/12/2024] Open
Abstract
Adhesion molecules play critical roles in maintaining the structural integrity of the airway epithelium in airways under stress. Previously, we reported that catenin alpha-like 1 (CTNNAL1) is downregulated in an asthma animal model and upregulated at the edge of human bronchial epithelial cells (HBECs) after ozone stress. In this work, we explore the potential role of CTNNAL1 in the structural adhesion of HBECs and its possible mechanism. We construct a CTNNAL1 ‒/‒ mouse model with CTNNAL1-RNAi recombinant adeno-associated virus (AAV) in the lung and a CTNNAL1-silencing cell line stably transfected with CTNNAL1-siRNA recombinant plasmids. Hematoxylin and eosin (HE) staining reveals that CTNNAL1 ‒/‒ mice have denuded epithelial cells and structural damage to the airway. Silencing of CTNNAL1 in HBECs inhibits cell proliferation and weakens extracellular matrix adhesion and intercellular adhesion, possibly through the action of the cytoskeleton. We also find that the expressions of the structural adhesion-related molecules E-cadherin, integrin β1, and integrin β4 are significantly decreased in ozone-treated cells than in vector control cells. In addition, our results show that the expression levels of RhoA/ROCK1 are decreased after CTNNAL1 silencing. Treatment with Y27632, a ROCK inhibitor, abolished the expressions of adhesion molecules induced by ozone in CTNNAL1-overexpressing HBECs. Overall, the findings of the present study suggest that CTNNAL1 plays a critical role in maintaining the structural integrity of the airway epithelium under ozone challenge, and is associated with epithelial cytoskeleton dynamics and the expressions of adhesion-related molecules via the RhoA/ROCK1 pathway.
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Affiliation(s)
- Caixia Liu
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral DiseasesHunan University of Chinese MedicineChangsha410208China
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Jinmei Wang
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Yurong Tan
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Chi Liu
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Xiangping Qu
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Huijun Liu
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Meiling Tan
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Changqing Deng
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral DiseasesHunan University of Chinese MedicineChangsha410208China
| | - Xiaoqun Qin
- School of Basic MedicineCentral South UniversityChangsha410078China
| | - Yang Xiang
- School of Basic MedicineCentral South UniversityChangsha410078China
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9
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Rabiet L, Arakelian L, Jeger-Madiot N, García DR, Larghero J, Aider JL. Acoustic levitation as a tool for cell-driven self-organization of human cell spheroids during long-term 3D culture. Biotechnol Bioeng 2024; 121:1422-1434. [PMID: 38225905 DOI: 10.1002/bit.28651] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 12/14/2023] [Accepted: 12/20/2023] [Indexed: 01/17/2024]
Abstract
Acoustic levitation, which allows contactless manipulation of micro-objects with ultrasounds, is a promising technique for spheroids formation and culture. This acoustofluidic technique favors cell-cell interactions, away from the walls of the chip, which leads to the spontaneous self-organization of cells. Using this approach, we generated spheroids of mesenchymal stromal cells, hepatic and endothelial cells, and showed that long-term culture of cells in acoustic levitation is feasible. We also demonstrated that this self-organization and its dynamics depended weakly on the acoustic parameters but were strongly dependent on the levitated cell type. Moreover, spheroid organization was modified by actin cytoskeleton inhibitors or calcium-mediated interaction inhibitors. Our results confirmed that acoustic levitation is a rising technique for fundamental research and biotechnological industrial application in the rapidly growing field of microphysiological systems. It allowed easily obtaining spheroids of specific and predictable shape and size, which could be cultivated over several days, without requiring hydrogels or extracellular matrix.
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Affiliation(s)
- Lucile Rabiet
- Laboratoire Physique et mécanique des milieux Hétérogènes (PMMH), CNRS, ESPCI, Paris, France
- Inserm U976, CIC-BT CBT501, AP-HP, Université Paris-Cité, Hôpital Saint-Louis, Paris, France
| | - Lousineh Arakelian
- Inserm U976, CIC-BT CBT501, AP-HP, Université Paris-Cité, Hôpital Saint-Louis, Paris, France
| | - Nathan Jeger-Madiot
- Laboratoire Physique et mécanique des milieux Hétérogènes (PMMH), CNRS, ESPCI, Paris, France
| | - Duván Rojas García
- Laboratoire Physique et mécanique des milieux Hétérogènes (PMMH), CNRS, ESPCI, Paris, France
| | - Jérôme Larghero
- Inserm U976, CIC-BT CBT501, AP-HP, Université Paris-Cité, Hôpital Saint-Louis, Paris, France
| | - Jean-Luc Aider
- Laboratoire Physique et mécanique des milieux Hétérogènes (PMMH), CNRS, ESPCI, Paris, France
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Guo H, Zhou C, Zheng M, Zhang J, Wu H, He Q, Ding L, Yang B. Insights into the role of derailed endocytic trafficking pathway in cancer: From the perspective of cancer hallmarks. Pharmacol Res 2024; 201:107084. [PMID: 38295915 DOI: 10.1016/j.phrs.2024.107084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 01/12/2024] [Accepted: 01/25/2024] [Indexed: 02/06/2024]
Abstract
The endocytic trafficking pathway is a highly organized cellular program responsible for the regulation of membrane components and uptake of extracellular substances. Molecules internalized into the cell through endocytosis will be sorted for degradation or recycled back to membrane, which is determined by a series of sorting events. Many receptors, enzymes, and transporters on the membrane are strictly regulated by endocytic trafficking process, and thus the endocytic pathway has a profound effect on cellular homeostasis. However, the endocytic trafficking process is typically dysregulated in cancers, which leads to the aberrant retention of receptor tyrosine kinases and immunosuppressive molecules on cell membrane, the loss of adhesion protein, as well as excessive uptake of nutrients. Therefore, hijacking endocytic trafficking pathway is an important approach for tumor cells to obtain advantages of proliferation and invasion, and to evade immune attack. Here, we summarize how dysregulated endocytic trafficking process triggers tumorigenesis and progression from the perspective of several typical cancer hallmarks. The impact of endocytic trafficking pathway to cancer therapy efficacy is also discussed.
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Affiliation(s)
- Hongjie Guo
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Chen Zhou
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Mingming Zheng
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jie Zhang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Honghai Wu
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Qiaojun He
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; The Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou 310018, China; Cancer Center of Zhejiang University, Hangzhou 310058, China
| | - Ling Ding
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Nanhu Brain-computer Interface Institute, Hangzhou 311100, China.
| | - Bo Yang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; School of Medicine, Hangzhou City University, Hangzhou 310015, China; The Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou 310018, China.
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11
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Cai HQ, Zhang LY, Fu LM, Xu B, Jiao Y. Mutational landscape of TP53 and CDH1 in gastric cancer. World J Gastrointest Surg 2024; 16:276-283. [PMID: 38463349 PMCID: PMC10921187 DOI: 10.4240/wjgs.v16.i2.276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 12/26/2023] [Accepted: 01/30/2024] [Indexed: 02/25/2024] Open
Abstract
In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg. A common gene mutation in gastric cancer (GC) is the TP53 mutation. As a tumor suppressor gene, TP53 is implicated in more than half of all tumor occurrences. TP53 gene mutations in GC tissue may be related with clinical pathological aspects. The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy. CDH1 encodes E-cadherin, which is involved in cell-to-cell adhesion, epithelial structure maintenance, cell polarity, differentiation, and intracellular signaling pathway modulation. CDH1 mutations and functional loss can result in diffuse GC, and CDH1 mutations can serve as independent prognostic indicators for poor prognosis. GC patients can benefit from genetic counseling and testing for CDH1 mutations. Demethylation therapy may assist to postpone the onset and progression of GC. The investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations, as well as providing some basis for evaluating the prognosis of GC patients.
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Affiliation(s)
- Hong-Qiao Cai
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Li-Yue Zhang
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Li-Ming Fu
- Department of Traditional Chinese Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Bin Xu
- Department of Traditional Chinese Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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12
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de Ponthaud C, Abdalla S, Belot MP, Shao X, Penna C, Brouquet A, Bougnères P. Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease. Clin Epigenetics 2024; 16:28. [PMID: 38355645 PMCID: PMC10865720 DOI: 10.1186/s13148-024-01631-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 01/18/2024] [Indexed: 02/16/2024] Open
Abstract
BACKGROUND E-cadherin, a major actor of cell adhesion in the intestinal barrier, is encoded by the CDH1 gene associated with susceptibility to Crohn Disease (CD) and colorectal cancer. Since epigenetic mechanisms are suspected to contribute to the multifactorial pathogenesis of CD, we studied CpG methylation at the CDH1 locus. The methylation of the CpG island (CGI) and of the 1st enhancer, two critical regulatory positions, was quantified in surgical specimens of inflamed ileal mucosa and in peripheral blood mononuclear cells (PBMC) of 21 CD patients. Sixteen patients operated on for a non-inflammatory bowel disease, although not normal controls, provided a macroscopically normal ileal mucosa and PBMC for comparison. RESULTS In ileal mucosa, 19/21 (90%) CD patients vs 8/16 control patients (50%) (p < 0.01) had a methylated CDH1 promoter CGI. In PBMC, CD patients with methylated CGI were 11/21 (52%) vs 7/16 controls (44%), respectively. Methylation in the 1st enhancer of CDH1 was also higher in the CD group for each of the studied CpGs and for their average value (45 ± 17% in CD patients vs 36 ± 17% in controls; p < 0.001). Again, methylation was comparable in PBMC. Methylation of CGI and 1st enhancer were not correlated in mucosa or PBMC. CONCLUSIONS Methylation of several CpGs at the CDH1 locus was increased in the inflamed ileal mucosa, not in the PBMC, of CD patients, suggesting the association of CDH1 methylation with ileal inflammation. Longitudinal studies will explore if this increased methylation is a risk marker for colorectal cancer.
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Affiliation(s)
- Charles de Ponthaud
- Department of Visceral and Digestive Surgery, Hôpital Bicêtre AP-HP, Paris Saclay University, 94276, Le Kremlin-Bicêtre Cedex, France
- UMR INSERM 1169 and Université Paris Saclay, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France
| | - Solafah Abdalla
- Department of Visceral and Digestive Surgery, Hôpital Bicêtre AP-HP, Paris Saclay University, 94276, Le Kremlin-Bicêtre Cedex, France
- UMR INSERM 1169 and Université Paris Saclay, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France
| | - Marie-Pierre Belot
- Groupe d'Études sur le Diabète, l'Obésité, la Croissance, GETDOC, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France
| | - Xiaojian Shao
- Digital Technologies Research Center, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada
| | - Christophe Penna
- Department of Visceral and Digestive Surgery, Hôpital Bicêtre AP-HP, Paris Saclay University, 94276, Le Kremlin-Bicêtre Cedex, France
| | - Antoine Brouquet
- Department of Visceral and Digestive Surgery, Hôpital Bicêtre AP-HP, Paris Saclay University, 94276, Le Kremlin-Bicêtre Cedex, France
| | - Pierre Bougnères
- UMR INSERM 1169 and Université Paris Saclay, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France.
- Groupe d'Études sur le Diabète, l'Obésité, la Croissance, GETDOC, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre Cedex, France.
- MIRCEN Institute, CEA Paris-Saclay/site de Fontenay-aux-Roses, Bâtiment 56 PC 103, 18 route du Panorama, BP6 92265, Fontenay-aux-Roses Cedex, France.
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13
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Yang F, Hu Y, Shi Z, Liu M, Hu K, Ye G, Pang Q, Hou R, Tang K, Zhu Y. The occurrence and development mechanisms of esophageal stricture: state of the art review. J Transl Med 2024; 22:123. [PMID: 38297325 PMCID: PMC10832115 DOI: 10.1186/s12967-024-04932-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 01/26/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention. METHODS A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles. RESULTS Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures. CONCLUSION The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.
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Affiliation(s)
- Fang Yang
- Health Science Center, Ningbo University, Ningbo, 315211, People's Republic of China
| | - Yiwei Hu
- Health Science Center, Ningbo University, Ningbo, 315211, People's Republic of China
| | - Zewen Shi
- Health Science Center, Ningbo University, Ningbo, 315211, People's Republic of China
- Ningbo No.2 Hospital, Ningbo, 315001, People's Republic of China
| | - Mujie Liu
- Health Science Center, Ningbo University, Ningbo, 315211, People's Republic of China
| | - Kefeng Hu
- The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China
| | - Guoliang Ye
- The First Affiliated Hospital of Ningbo University, Ningbo, 315000, People's Republic of China
| | - Qian Pang
- Health Science Center, Ningbo University, Ningbo, 315211, People's Republic of China
| | - Ruixia Hou
- Health Science Center, Ningbo University, Ningbo, 315211, People's Republic of China
| | - Keqi Tang
- Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, 315211, People's Republic of China.
| | - Yabin Zhu
- Health Science Center, Ningbo University, Ningbo, 315211, People's Republic of China.
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14
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Abak N, Azad M, Ali FM, Saberian M, Turkaman S, Alizadeh S. DNA Methylation Pattern and mRNA Expression Level of E-Cadherin and P16 Genes in Thrombotic Disorders. Clin Appl Thromb Hemost 2024; 30:10760296241300490. [PMID: 39711001 DOI: 10.1177/10760296241300490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2024] Open
Abstract
OBJECTIVE DNA methylation, as an epigenetic alteration, plays an essential role in the development of atherosclerosis and venous thrombosis. E-cadherin, a tumor suppressor gene and adhesion molecule, has a crucial function in platelet aggregation and hemostasis. P16, a cell cycle regulator, is involved in venous thrombosis. The aim of this study is to evaluate the DNA methylation patterns and expression levels of the E-cadherin and P16 genes in venous thromboembolism (VTE). METHOD Peripheral blood samples were collected from 32 patients, including those with deep vein thrombosis (DVT, n = 15), pulmonary embolism (PE, n = 8), DVT with PE (n = 4), intestinal thrombosis (IT, n = 3), and cerebral venous sinus thrombosis (CVST, n = 2), as well as from 10 healthy individuals. The DNA methylation patterns and gene expression levels of E-cadherin and P16 were analyzed using methylation-specific PCR (MSP) and Real-Time PCR, respectively. RESULTS The promoter of the CDH1 gene was partially methylated in 84.4% of thrombotic patients and unmethylated in 15.6% (P = 0.183). A significantly higher expression level of CDH1 was observed in the patients compared to the controls (P = 0.001). The P16 gene promoter were unmethylated in all control and patient specimens. Compared to normal subjects, the expression level of the P16 was significantly increased in patients (P = 0.000). CONCLUSION Our results indicated that DNA methylation is not the main gene expression regulatory mechanism for E-cadherin and P16 genes in thrombosis. Higher transcription levels of CDH1 and P16 in thrombotic patients may show their crucial roles in the pathogenesis of VTE.
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Affiliation(s)
- Niloofar Abak
- Department of Hematology and Transfusion sciences, School of Allied Medical Sciences, Tehran University of Medical sciences, Tehran, Iran
| | - Mehdi Azad
- Department of Medical laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Fatemeh Mohammad Ali
- Iranian Blood Transfusion Research Center, Hight Institute for Education and Research in Transfusion Medicine, Tehran, Iran
| | - Mostafa Saberian
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Turkaman
- Mashhad University of Medical Sciences, School of Allied Medical Sciences, Mashhad, Iran
| | - Shaban Alizadeh
- Department of Hematology and Transfusion sciences, School of Allied Medical Sciences, Tehran University of Medical sciences, Tehran, Iran
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15
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Negrutskii BS, Porubleva LV, Malinowska A, Novosylna OV, Dadlez M, Knudsen CR. Understanding functions of eEF1 translation elongation factors beyond translation. A proteomic approach. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 138:67-99. [PMID: 38220433 DOI: 10.1016/bs.apcsb.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2024]
Abstract
Mammalian translation elongation factors eEF1A1 and eEF1A2 are 92% homologous isoforms whose mutually exclusive tissue-specific expression is regulated during development. The isoforms have similar translation functionality, but show differences in spatial organization and participation in various processes, such as oncogenesis and virus reproduction. The differences may be due to their ability to interact with isoform-specific partner proteins. We used the identified sets of eEF1A1 or eEF1A2 partner proteins to identify cell complexes and/or processes specific to one particular isoform. As a result, we found isoform-specific interactions reflecting the involvement of different eEF1A isoforms in different cellular processes, including actin-related, chromatin-remodeling, ribonuclease H2, adenylyl cyclase, and Cul3-RING ubiquitin ligase complexes as well as initiation of mitochondrial transcription. An essential by-product of our analysis is the elucidation of a number of cellular processes beyond protein biosynthesis, where both isoforms appear to participate such as large ribosomal subunit biogenesis, mRNA splicing, DNA mismatch repair, 26S proteasome activity, P-body and exosomes formation, protein targeting to the membrane. This information suggests that a relatively high content of eEF1A in the cell may be necessary not only to maintain efficient translation, but also to ensure its participation in various cellular processes, where some roles of eEF1A have not yet been described. We believe that the data presented here will be useful for deciphering new auxiliary functions of eEF1A and its isoforms, and provide a new look at the known non-canonical functions of this main component of the human translation-elongation machinery.
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Affiliation(s)
- Boris S Negrutskii
- Institute of Molecular Biology and Genetics, Kyiv, Ukraine; Aarhus Institute of Advanced Sciences, Høegh-Guldbergs, Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen, Aarhus C, Denmark.
| | | | - Agata Malinowska
- Institute of Biochemistry and Biophysics, PAN, Pawinskiego, Warsaw, Poland
| | | | - Michal Dadlez
- Institute of Biochemistry and Biophysics, PAN, Pawinskiego, Warsaw, Poland
| | - Charlotte R Knudsen
- Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen, Aarhus C, Denmark
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16
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Sun S, Xu Z, Hu H, Zheng M, Zhang L, Xie W, Sun L, Liu P, Li T, Zhang L, Chen M, Zhu X, Liu M, Yang Y, Zhou J. The Bacillus cereus toxin alveolysin disrupts the intestinal epithelial barrier by inducing microtubule disorganization through CFAP100. Sci Signal 2023; 16:eade8111. [PMID: 37192300 DOI: 10.1126/scisignal.ade8111] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 04/18/2023] [Indexed: 05/18/2023]
Abstract
Bacillus cereus is a Gram-positive bacterium that mainly causes self-limiting emetic or diarrheal illness but can also cause skin infections and bacteremia. Symptoms of B. cereus ingestion depend on the production of various toxins that target the gastric and intestinal epithelia. From a screen of bacterial isolates from human stool samples that compromised intestinal barrier function in mice, we identified a strain of B. cereus that disrupted tight and adherens junctions in the intestinal epithelium. This activity was mediated by the pore-forming exotoxin alveolysin, which increased the production of the membrane-anchored protein CD59 and of cilia- and flagella-associated protein 100 (CFAP100) in intestinal epithelial cells. In vitro, CFAP100 interacted with microtubules and promoted microtubule polymerization. CFAP100 overexpression stabilized microtubules in intestinal epithelial cells, leading to disorganization of the microtubule network and perturbation of tight and adherens junctions. The disruption of cell junctions by alveolysin depended on the increase in CFAP100, which in turn depended on CD59 and the activation of PI3K-AKT signaling. These findings demonstrate that, in addition to forming membrane pores, B. cereus alveolysin can permeabilize the intestinal epithelium by disrupting epithelial cell junctions in a manner that is consistent with intestinal symptoms and may allow the bacteria to escape the intestine and cause systemic infections. Our results suggest the potential value of targeting alveolysin or CFAP100 to prevent B. cereus-associated intestinal diseases and systemic infections.
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Affiliation(s)
- Shuang Sun
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Zhaoyang Xu
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Haijie Hu
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Manxi Zheng
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Liang Zhang
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Wei Xie
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Lei Sun
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Peiwei Liu
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Tianliang Li
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Liangran Zhang
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Min Chen
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
| | - Xueliang Zhu
- State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
| | - Min Liu
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Yunfan Yang
- Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Jun Zhou
- Center for Cell Structure and Function, Haihe Laboratory of Cell Ecosystem, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan 250014, China
- State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China
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Niu ZS, Wang WH, Niu XJ. Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma. World J Gastroenterol 2022; 28:6433-6477. [PMID: 36569275 PMCID: PMC9782839 DOI: 10.3748/wjg.v28.i46.6433] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 10/31/2022] [Accepted: 11/21/2022] [Indexed: 12/08/2022] Open
Abstract
Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.
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Affiliation(s)
- Zhao-Shan Niu
- Laboratory of Micromorphology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Wen-Hong Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Xiao-Jun Niu
- Department of Internal Medicine, Qingdao Shibei District People's Hospital, Qingdao 266033, Shandong Province, China
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Takeichi M. Cell sorting in vitro and in vivo: How are cadherins involved? Semin Cell Dev Biol 2022; 147:2-11. [PMID: 36376196 DOI: 10.1016/j.semcdb.2022.11.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/07/2022] [Accepted: 11/07/2022] [Indexed: 11/13/2022]
Abstract
Animal tissues are composed of heterogenous cells, and their sorting into different compartments of the tissue is a pivotal process for organogenesis. Cells accomplish sorting by themselves-it is well known that singly dispersed cells can self-organize into tissue-like structures in vitro. Cell sorting is regulated by both biochemical and physical mechanisms. Adhesive proteins connect cells together, selecting particular partners through their specific binding properties, while physical forces, such as cell-cortical tension, control the cohesiveness between cells and in turn cell assembly patterns in mechanical ways. These processes cooperate in determining the overall cell sorting behavior. This article focuses on the 'cadherin' family of adhesion molecules as a biochemical component of cell-cell interactions, addressing how they regulate cell sorting by themselves or by cooperating with other factors. New ideas beyond the classical models of cell sorting are also discussed.
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Chang L, Wang D, Kan S, Hao M, Liu H, Yang Z, Xia Q, Liu W. Ginsenoside Rd inhibits migration and invasion of tongue cancer cells through H19/miR-675-5p/CDH1 axis. J Appl Oral Sci 2022; 30:e20220144. [PMID: 36074434 PMCID: PMC9444189 DOI: 10.1590/1678-7757-2022-0144] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 07/18/2022] [Indexed: 11/27/2022] Open
Abstract
Objective Tongue squamous cell carcinoma (TSCC) is an oral cancer, with high malignancy and frequent early migration and invasion. Only a few drugs can treat tongue cancer. Ginsenoside Rd is a ginseng extract with anti-cancer effects. Many noncoding RNAs are abnormally expressed in tongue cancer, thus influencing its occurrence and development. H19 and miR-675-5p can promote cancer cell growth. This study aimed to analyze the regulation effect of ginsenoside Rd on H19 and miR-675-5p in tongue cancer. Methodology We used CCK8 and flow cytometry to study the growth and apoptosis. Transwell assay was used to assess invasion; wound-healing assay to assess migration; and colony formation assays to test the ability of cells to form colonies. H19, miR-675-5p, and CDH1 expressions were analyzed by qPCR. E-cadherin expression was detected using western blot. CRISPR/cas9 system was used for CDH1 knockout. Results Ginsenoside Rd inhibited the growth and increased the apoptosis of SCC9 cells. Ginsenoside Rd also inhibited the migration and invasion of SCC9 cells. H19 and miR-675-5p were highly expressed, while CDH1 and E-cadherin expressions were low. H19 and miR-675-5p promoted SCC9 metastasis. In contrast, CDH1 and E-cadherin inhibited the metastasis of SCC9 cells. Bioinformatics analysis showed that miR-675-5p was associated with CDH1. H19 and miR-675-5p expressions decreased after ginsenoside Rd treatment, while CDH1 and E-cadherin expressions increased. Conclusions Ginsenoside Rd inhibits tongue cancer cell migration and invasion via the H19/miR-675-5p/CDH1 axis.
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Affiliation(s)
- Lu Chang
- Jilin University, Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Changchun, China.,Jilin University, College of Animal Science, Laboratory Animal Center, Changchun, China.,Jilin University, Hospital of Stomatology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun, China
| | - Dongxu Wang
- Jilin University, College of Animal Science, Laboratory Animal Center, Changchun, China
| | - Shaoning Kan
- Jilin University, Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Changchun, China
| | - Ming Hao
- Jilin University, Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Changchun, China
| | - Huimin Liu
- Jilin University, Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Changchun, China
| | - Zhijing Yang
- Jilin University, Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Changchun, China
| | - Qianyun Xia
- Jilin University, College of Animal Science, Laboratory Animal Center, Changchun, China
| | - Weiwei Liu
- Jilin University, Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Changchun, China
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Hereditary Diffuse Gastric Cancer: Molecular Genetics, Biological Mechanisms and Current Therapeutic Approaches. Int J Mol Sci 2022; 23:ijms23147821. [PMID: 35887173 PMCID: PMC9319245 DOI: 10.3390/ijms23147821] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/01/2022] [Accepted: 07/06/2022] [Indexed: 12/14/2022] Open
Abstract
Hereditary diffuse gastric cancer is an autosomal dominant syndrome characterized by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is caused by inactivating mutations in the tumor suppressor gene CDH1. Genetic testing technologies have become more efficient over the years, also enabling the discovery of other susceptibility genes for gastric cancer, such as CTNNA1 among the most important genes. The diagnosis of pathogenic variant carriers with an increased risk of developing gastric cancer is a selection process involving a multidisciplinary team. To achieve optimal long-term results, it requires shared decision-making in risk management. In this review, we present a synopsis of the molecular changes and current therapeutic approaches in HDGC based on the current literature.
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Kaurin D, Bal PK, Arroyo M. Peeling dynamics of fluid membranes bridged by molecular bonds: moving or breaking. J R Soc Interface 2022; 19:20220183. [PMID: 35765808 PMCID: PMC9240675 DOI: 10.1098/rsif.2022.0183] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 06/01/2022] [Indexed: 11/28/2022] Open
Abstract
Biological adhesion is a critical mechanical function of complex organisms. At the scale of cell-cell contacts, adhesion is remarkably tunable to enable both cohesion and malleability during development, homeostasis and disease. It is physically supported by transient and laterally mobile molecular bonds embedded in fluid membranes. Thus, unlike specific adhesion at solid-solid or solid-fluid interfaces, peeling at fluid-fluid interfaces can proceed by breaking bonds, by moving bonds or by a combination of both. How the additional degree of freedom provided by bond mobility changes the mechanics of peeling is not understood. To address this, we develop a theoretical model coupling diffusion, reactions and mechanics. Mobility and reaction rates determine distinct peeling regimes. In a diffusion-dominated Stefan-like regime, bond motion establishes self-stabilizing dynamics that increase the effective fracture energy. In a reaction-dominated regime, peeling proceeds by travelling fronts where marginal diffusion and unbinding control peeling speed. In a mixed reaction-diffusion regime, strengthening by bond motion competes with weakening by bond breaking in a force-dependent manner, defining the strength of the adhesion patch. In turn, patch strength depends on molecular properties such as bond stiffness, force sensitivity or crowding. We thus establish the physical rules enabling tunable cohesion in cellular tissues and in engineered biomimetic systems.
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Affiliation(s)
- Dimitri Kaurin
- Universitat Politècnica de Catalunya-BarcelonaTech, 08034 Barcelona, Spain
| | - Pradeep K. Bal
- Universitat Politècnica de Catalunya-BarcelonaTech, 08034 Barcelona, Spain
| | - Marino Arroyo
- Universitat Politècnica de Catalunya-BarcelonaTech, 08034 Barcelona, Spain
- Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, 08034 Barcelona, Spain
- CIMNE, 08034 Barcelona, Spain
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Yang J, Lu F, Ma G, Pang Y, Zhao Y, Sun T, Ma D, Ye J, Ji C. Role of CDH23 as a prognostic biomarker and its relationship with immune infiltration in acute myeloid leukemia. BMC Cancer 2022; 22:568. [PMID: 35597916 PMCID: PMC9123811 DOI: 10.1186/s12885-022-09532-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 04/12/2022] [Indexed: 11/10/2022] Open
Abstract
Background Cadherin-23 (CDH23) plays an important role in intercellular adhesion and is involved in the progression of several types of cancer. However, the biological functions and effect of CDH23 expression on the prognosis of patients with acute myeloid leukemia (AML) are unexplored. Herein, we aim to characterize the role and molecular functions of CDH23 in AML. Methods We downloaded the transcriptomic profiles and clinical data from the Cancer Genome Atlas and Beat AML trial. The expression level of CDH23 was assessed using Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier survival analysis was used to assess prognostic value of CDH23. Correlation and biological function analyses were performed using LinkedOmics and GeneMANIA. Relationship of CDH23 with immune infiltration level was determined using Tumor Immune Estimation Resource (TIMER). Results We found that the CDH23 expression was aberrantly upregulated in patients with AML and could be used as an independent risk factor of overall survival using Cox multivariate analysis. Notably, we observed a negative correlation between CDH23 expression and immune cell infiltration abundance by calculating the immune and stromal scores. In addition, functional enrichment analysis established that CDH23 plays a crucial role in tumor immunity. Conclusions Our findings indicate that upregulated CDH23 expression corresponds to decreased overall survival of patients with AML. CDH23 may be involved in mediating tumor immune environment, and this highlights the potential of CDH23 as a therapeutic target in AML. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09532-1.
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Affiliation(s)
- Jiao Yang
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Fei Lu
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Guangxin Ma
- Hematology and Oncology Unit, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Yihua Pang
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Yanan Zhao
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Tao Sun
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Daoxin Ma
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Jingjing Ye
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China
| | - Chunyan Ji
- Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
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Qiu P, Lin X, Deng G. [Talin1 is highly expressed in the fallopian tube and chorionic villi to promote trophoblast invasion in tubal pregnancy]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2022; 42:610-617. [PMID: 35527499 DOI: 10.12122/j.issn.1673-4254.2022.04.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the expression of Talin1 in the fallopian tube and chorionic villi in patients with tubal pregnancy and its role in regulating invasion and migration of trophoblasts. METHODS Immunohistochemistry and Western blotting were used to detect the localization and expression level of Talin1 in the fallopian tube and chorionic villi in patients with tubal pregnancy and in women with normal pregnancy. In the cell experiment, HTR-8/SVneo cells was transfected with Talin1 siRNA and the changes in cell invasion and migration were assessed using scratch assay and Transwell assay. The expressions of MMP-2, MMP-9, N-cadherin and Snail in the transfected cells were detected by qRT-PCR and Western blotting. RESULTS Positive expression of Talin1 was detected in both normal fallopian tube tissues and tissues from women tubal pregnancy, and its expression was localized mainly in the cytoplasm of cilia cells. The expression level of Talin1 was significantly higher in both the fallopian tube and chorionic villi in women with tubal pregnancy than in normal fallopian tube and chorionic villi samples (P < 0.01). In HTR-8/SVneo cells, transfection with Talin1 siRNA significantly inhibited cell invasion (P < 0.01) and migration (P < 0.05), down-regulated the expression of N-cadherin, MMP-2 and Snail (P < 0.05), and up-regulated the expression of MMP-9 in the cells (P < 0.05). CONCLUSION The expression of Talin1 in the fallopian tube and chorionic villi is significantly increased in women with tubal pregnancy, suggesting the association of Talin1-regulated trophoblast cell invasion with the occurrence of tubal pregnancy.
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Affiliation(s)
- P Qiu
- Department of Gynecology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - X Lin
- First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - G Deng
- Department of Gynecology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China
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Peng F, Wang L, Xiong L, Tang H, Du J, Peng C. Maackiain Modulates miR-374a/GADD45A Axis to Inhibit Triple-Negative Breast Cancer Initiation and Progression. Front Pharmacol 2022; 13:806869. [PMID: 35308218 PMCID: PMC8930825 DOI: 10.3389/fphar.2022.806869] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/24/2022] [Indexed: 12/20/2022] Open
Abstract
Breast cancer ranks as the leading cause of death in lethal malignancies among women worldwide, with a sharp increase of incidence since 2008. Triple negative breast cancer (TNBC) gives rise to the largest proportion in breast cancer-related deaths because of its aggressive growth and rapid metastasis. Hence, searching for promising targets and innovative approaches is indispensable for the TNBC treatment. Maackiain (MA), a natural compound with multiple biological activities, could be isolated from different Chinese herbs, such as Spatholobus suberectus and Sophora flavescens. It was the first time to report the anti-cancer effect of MA in TNBC. MA could suppress TNBC cell proliferation, foci formation, migration, and invasion. MA also exerted a significant inhibitory effect on tumor growth of TNBC. Furthermore, MA could induce apoptosis with an increase of GADD45α and a decrease of miR-374a. In contrast, overexpressing miR-374a would result in at least partly affecting the proapoptotic effect of MA and suppressing GADD45α stimulated by MA. These results reveal the anti-TNBC effect of MA in vitro and in vivo, providing evidence for its potential as a drug candidate utilized in TNBC therapy.
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Affiliation(s)
- Fu Peng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Li Wang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Liang Xiong
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hailin Tang
- Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Junrong Du
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
- *Correspondence: Cheng Peng, ; Junrong Du,
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Cheng Peng, ; Junrong Du,
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Xie SZ, Zhai XY, Xi SY, Qiu YK, Zhang YM, Kong XJ, Li YH, Zhu L, Wang Z, Zhang SG, Huang SQ, Lu DW, Wang Z. The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice. Front Pharmacol 2021; 12:764282. [PMID: 34899319 PMCID: PMC8651617 DOI: 10.3389/fphar.2021.764282] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 11/10/2021] [Indexed: 12/31/2022] Open
Abstract
Background:Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI). Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms. Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined. Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1β, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI. Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.
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Affiliation(s)
- Su-Zhi Xie
- Department of Pharmacy, Xiamen Haicang Hospital, Xiamen, China
| | - Xiang-Yang Zhai
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Sheng-Yan Xi
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China.,Department of Traditional Chinese Medicine, Xiang'an Hospital of Xiamen University, Xiamen, China
| | - Ying-Kun Qiu
- School of Pharmaceutical Sciences, Xiamen University, Xiamen, China
| | - Yu-Mei Zhang
- Department of Traditional Chinese Medicine, Xiang'an Hospital of Xiamen University, Xiamen, China
| | - Xiang-Jun Kong
- Department of Pharmacy, Xiang'an Hospital of Xiamen University, Xiamen, China
| | - Yun-Hong Li
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Lin Zhu
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Zheng Wang
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Shan-Gang Zhang
- Department of Traditional Chinese Medicine, Xiang'an Hospital of Xiamen University, Xiamen, China
| | - Shu-Qiong Huang
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Da-Wei Lu
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Zheng Wang
- Department of Pharmacy, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
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Wang J, Liu S, Pan T, Wang M, Li L, Weng X, Jia P, Li Q, Zhou X. Long non-coding RNA ZNF674-AS1 regulates miR-23a/E-cadherin axis to suppress the migration and invasion of non-small cell lung cancer cells. Transl Cancer Res 2021; 10:4116-4124. [PMID: 35116709 PMCID: PMC8798196 DOI: 10.21037/tcr-21-1499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/30/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. The prognosis of patients with advanced NSCLC is poor due to metastasis. In recent years, the role of long non-coding RNAs (lncRNAs), a class of non-coding RNA molecules, in NSCLC has become an increasingly popular focus of studies. This study aimed to investigate the effects of ZNF674-AS1 and microRNA (miR)-23a on the migration and invasion abilities of NSCLC cells in vitro and explore the underpinning molecular mechanisms. METHODS The expression levels of ZNF674-AS1 and miR-23a in NSCLC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Scratch test and transwell test were used to detect the effects of ZNF674-AS1 and miR-23a on the migration and invasion of NSCLC cells. The luciferase reporter gene experiment was used to verify miRNA targets. Western blot experiments were used to analyze protein expression. RESULTS ZNF674-AS1 was downregulated in NSCLC tissues and cells, and inhibited the migration and invasion of NSCLC cells in vitro. In contrast, the expression of miR-23a, a downstream target of ZNF674-AS1, was increased in NSCLC tissues and cells. We found that miR-23a could antagonize the role of ZNF674-AS1 in NSCLC. E-cadherin was identified as a downstream target gene of miR-23a, and miR-23a could directly inhibit its expression. CONCLUSIONS ZNF674-AS1 inhibits the migration and invasion of NSCLC cells by regulating a miR-23a/E-cadherin axis. ZNF674-AS1 and miR-23a could become potential therapeutic targets for NSCLC.
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Affiliation(s)
- Jie Wang
- Nanjing Medical University, Nanjing, China
- Department of Respiratory Diseases, the First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Sha Liu
- Department of Radiotherapy, the First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Tao Pan
- Department of Radiotherapy, the First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Mingkun Wang
- Department of Radiotherapy, the First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Liang Li
- Department of Respiratory Diseases, the First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Xiangqian Weng
- Department of Radiotherapy, the First Affiliated Hospital of Hainan Medical University, Haikou, China
| | | | - Qi Li
- Department of Respiratory Diseases, the First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Xiangdong Zhou
- Nanjing Medical University, Nanjing, China
- Department of Respiratory Diseases, the First Affiliated Hospital of Hainan Medical University, Haikou, China
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Zhao H, Hu H, Chen B, Xu W, Zhao J, Huang C, Xing Y, Lv H, Nie C, Wang J, He Y, Wang SQ, Chen XB. Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications. Front Mol Biosci 2021; 8:689139. [PMID: 34422902 PMCID: PMC8371966 DOI: 10.3389/fmolb.2021.689139] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 07/19/2021] [Indexed: 01/04/2023] Open
Abstract
Gastric cancer is the fifth most common cancer and the third most common cause of cancer death all over the world. E-cadherin encoded by human CDH1 gene plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. Full-length E-cadhrin tethered on the cell membrane mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. After proteolysis, the extracellular fragment of the full-length E-cadhein is released into the extracellular environment and the blood, which is called soluble E-cadherin (sE-cadherin). sE-cadherin promots invasion and metastasis as a paracrine/autocrine signaling molecule in the progression of various types of cancer including gastric cancer. This review mainly summarizes the dysregulation of E-cadherin and the regulatory roles in the progression, invasion, metastasis, and drug-resistance, as well as its clinical applications in diagnosis, prognosis, and therapeutics of gastric cancer.
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Affiliation(s)
- Huichen Zhao
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Huihui Hu
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Beibei Chen
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
| | - Weifeng Xu
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Jing Zhao
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Chen Huang
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Yishu Xing
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Huifang Lv
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Caiyun Nie
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Jianzheng Wang
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Yunduan He
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Sai-Qi Wang
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
| | - Xiao-Bing Chen
- Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China
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Chen Z, Oh D, Biswas KH, Zaidel-Bar R, Groves JT. Probing the effect of clustering on EphA2 receptor signaling efficiency by subcellular control of ligand-receptor mobility. eLife 2021; 10:67379. [PMID: 34414885 PMCID: PMC8397371 DOI: 10.7554/elife.67379] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 08/19/2021] [Indexed: 11/29/2022] Open
Abstract
Clustering of ligand:receptor complexes on the cell membrane is widely presumed to have functional consequences for subsequent signal transduction. However, it is experimentally challenging to selectively manipulate receptor clustering without altering other biochemical aspects of the cellular system. Here, we develop a microfabrication strategy to produce substrates displaying mobile and immobile ligands that are separated by roughly 1 µm, and thus experience an identical cytoplasmic signaling state, enabling precision comparison of downstream signaling reactions. Applying this approach to characterize the ephrinA1:EphA2 signaling system reveals that EphA2 clustering enhances both receptor phosphorylation and downstream signaling activity. Single-molecule imaging clearly resolves increased molecular binding dwell times at EphA2 clusters for both Grb2:SOS and NCK:N-WASP signaling modules. This type of intracellular comparison enables a substantially higher degree of quantitative analysis than is possible when comparisons must be made between different cells and essentially eliminates the effects of cellular response to ligand manipulation.
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Affiliation(s)
- Zhongwen Chen
- Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, China.,Department of Chemistry, University of California, Berkeley, Berkeley, United States
| | - Dongmyung Oh
- Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Galveston, United States.,Mechanobiology Institute, National University of Singapore, Singapore, Singapore
| | - Kabir Hassan Biswas
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
| | - Ronen Zaidel-Bar
- Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Jay T Groves
- Department of Chemistry, University of California, Berkeley, Berkeley, United States
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29
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Kandilogiannakis L, Filidou E, Drygiannakis I, Tarapatzi G, Didaskalou S, Koffa M, Arvanitidis K, Bamias G, Valatas V, Paspaliaris V, Kolios G. Development of a Human Intestinal Organoid Model for In Vitro Studies on Gut Inflammation and Fibrosis. Stem Cells Int 2021; 2021:9929461. [PMID: 34354753 PMCID: PMC8331310 DOI: 10.1155/2021/9929461] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 06/08/2021] [Accepted: 07/01/2021] [Indexed: 12/13/2022] Open
Abstract
Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal inflammation and fibrosis, the latter being the predominant denominator for long-term complications. Epithelial and mesenchymal 2D cultures are highly utilized in vitro models for the preclinical evaluation of anti-inflammatory and antifibrotic therapies. More recently, human intestinal organoids (HIOs), a new 3D in vitro model derived from pluripotent stem cells, have the advantage to closely resemble the architecture of the intestinal mucosa. However, the appropriate timing for the study of inflammatory and fibrotic responses, during HIO development, has not been adequately investigated. We developed HIOs from the human embryonic stem cell line, H1, and examined the expression of mesenchymal markers during their maturation process. We also investigated the effect of inflammatory stimuli on the expression of fibrotic and immunological mediators. Serial evaluation of the expression of mesenchymal and extracellular matrix (ECM) markers revealed that HIOs have an adequately developed mesenchymal component, which gradually declines through culture passages. Specifically, CD90, collagen type I, collagen type III, and fibronectin were highly expressed in early passages but gradually diminished in late passages. The proinflammatory cytokines IL-1α and TNF-α induced the mRNA expression of fibronectin, collagen types I and III, tissue factor (TF), and alpha-smooth muscle actin (α-SMA) primarily in early passages. Similarly, HIOs elicited strong mRNA and protein mesenchymal (CXCL10) and epithelial (CXCL1, CCL2, CXCL8, and CCL20) chemokine responses in early but not late passages. In contrast, the epithelial tight junction components, CLDN1 and JAMA, responded to inflammatory stimulation independently of the culture passage. Our findings indicate that this HIO model contains a functional mesenchymal component, during early passages, and underline the significance of the mesenchymal cells' fitness in inflammatory and fibrotic responses. Therefore, we propose that this model is suitable for the study of epithelial-mesenchymal interactions in early passages when the mesenchymal component is active.
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Affiliation(s)
- Leonidas Kandilogiannakis
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Eirini Filidou
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Ioannis Drygiannakis
- Gastroenterology and Hepatology Research Laboratory, Medical School, University of Crete, Heraklion, Greece
| | - Gesthimani Tarapatzi
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Stylianos Didaskalou
- Laboratory of Molecular Cell Biology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
| | - Maria Koffa
- Laboratory of Molecular Cell Biology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
| | - Konstantinos Arvanitidis
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Giorgos Bamias
- GI-Unit, Third Department of Internal Medicine, National & Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Vassilis Valatas
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
- Gastroenterology and Hepatology Research Laboratory, Medical School, University of Crete, Heraklion, Greece
| | | | - George Kolios
- Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
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30
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MicroRNAs in Epithelial-Mesenchymal Transition Process of Cancer: Potential Targets for Chemotherapy. Int J Mol Sci 2021; 22:ijms22147526. [PMID: 34299149 PMCID: PMC8305963 DOI: 10.3390/ijms22147526] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/07/2021] [Accepted: 07/10/2021] [Indexed: 12/12/2022] Open
Abstract
In the last decades, a kind of small non-coding RNA molecules, called as microRNAs, has been applied as negative regulators in various types of cancer treatment through down-regulation of their targets. More recent studies exert that microRNAs play a critical role in the EMT process of cancer, promoting or inhibiting EMT progression. Interestingly, accumulating evidence suggests that pure compounds from natural plants could modulate deregulated microRNAs to inhibit EMT, resulting in the inhibition of cancer development. This small essay is on the purpose of demonstrating the significance and function of microRNAs in the EMT process as oncogenes and tumor suppressor genes according to studies mainly conducted in the last four years, providing evidence of efficient target therapy. The review also summarizes the drug candidates with the ability to restrain EMT in cancer through microRNA regulation.
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31
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Liu M, Xu Y, Zhou Y, Lang R, Shi Z, Zhao J, Meng Y, Bao L. Integrated Analyses Reveal the Multi-Omics and Prognostic Characteristics of ATP5B in Breast Cancer. Front Genet 2021; 12:652474. [PMID: 34122507 PMCID: PMC8194306 DOI: 10.3389/fgene.2021.652474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 04/19/2021] [Indexed: 11/13/2022] Open
Abstract
The beta subunit of F1Fo-ATP synthase (ATP5B) has been demonstrated to play an essential role in tumor progression and metastasis. However, there has been no comprehensive pan-cancer multi-omics analysis of ATP5B, while the clinical relevance of ATP5B and its potential mechanism in regulating breast cancer are still poorly understood. In this study, we demonstrated that ATP5B has a higher frequency of amplification than deletion in most cancer types, and the copy number variation (CNV) of ATP5B was significantly positively correlated with its mRNA expression level. DNA methylation analysis across pan-cancer also revealed a strong correlation between ATP5B expression and epigenetic changes. We identified 6 significant methylation sites involved in the regulation of ATP5B expression. Tissue microarrays (TMA) from 129 breast cancer samples, integrated with multiple additional breast cancer dataset, were used to evaluate the ATP5B expression and its correlation with prognosis. Higher levels of ATP5B expression were consistently associated with a worse OS in all datasets, and Cox regression analysis suggested that ATP5B expression was an independent prognostic factor. Gene enrichment analysis indicated that the gene signatures of DNA damage recognition, the E-cadherin nascent pathway and the PLK1 pathway were enriched in ATP5B-high patients. Moreover, somatic mutation analysis showed that a significant different mutation frequency of CDH1 and ADAMTSL3 could be observed between the ATP5B-high and ATP5B-low groups. In conclusion, this study reveals novel significance regarding the genetic characteristics and clinical value of ATP5B highlighted in predicting the outcome of breast cancer patients.
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Affiliation(s)
- Min Liu
- Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.,The Graduate School, Tianjin Medical University, Tianjin, China
| | - Yuxuan Xu
- Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.,The Graduate School, Tianjin Medical University, Tianjin, China
| | - Yaoyao Zhou
- Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.,The Graduate School, Tianjin Medical University, Tianjin, China
| | - Ronggang Lang
- Department of Breast Cancer Pathology and Research Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Zhenyu Shi
- Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Jing Zhao
- Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Yuanyuan Meng
- Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.,The Graduate School, Tianjin Medical University, Tianjin, China
| | - Li Bao
- Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
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32
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Yang J, Zhang Y, Qin M, Cheng W, Wang W, Cao Y. Understanding and Regulating Cell-Matrix Interactions Using Hydrogels of Designable Mechanical Properties. J Biomed Nanotechnol 2021; 17:149-168. [PMID: 33785089 DOI: 10.1166/jbn.2021.3026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Similar to natural tissues, hydrogels contain abundant water, so they are considered as promising biomaterials for studying the influence of the mechanical properties of extracellular matrices (ECM) on various cell functions. In recent years, the growing research on cellular mechanical response has revealed that many cell functions, including cell spreading, migration, tumorigenesis and differentiation, are related to the mechanical properties of ECM. Therefore, how cells sense and respond to the extracellular mechanical environment has gained considerable attention. In these studies, hydrogels are widely used as the in vitro model system. Hydrogels of tunable stiffness, viscoelasticity, degradability, plasticity, and dynamical properties have been engineered to reveal how cells respond to specific mechanical features. In this review, we summarize recent process in this research direction and specifically focus on the influence of the mechanical properties of the ECM on cell functions, how cells sense and respond to the extracellular mechanical environment, and approaches to adjusting the stiffness of hydrogels.
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Affiliation(s)
- Jiapeng Yang
- Key Laboratory of Intelligent Optical Sensing and Integration, National Laboratory of Solid State Microstructure, and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China
| | - Yu Zhang
- Key Laboratory of Intelligent Optical Sensing and Integration, National Laboratory of Solid State Microstructure, and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China
| | - Meng Qin
- Key Laboratory of Intelligent Optical Sensing and Integration, National Laboratory of Solid State Microstructure, and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China
| | - Wei Cheng
- Department of Oral Implantology Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China
| | - Wei Wang
- Key Laboratory of Intelligent Optical Sensing and Integration, National Laboratory of Solid State Microstructure, and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China
| | - Yi Cao
- Key Laboratory of Intelligent Optical Sensing and Integration, National Laboratory of Solid State Microstructure, and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China
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33
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Peng F, Tang H, Du J, Chen J, Peng C. Isoliquiritigenin Suppresses EMT-Induced Metastasis in Triple-Negative Breast Cancer through miR-200c/C-JUN/
β
-Catenin. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2021; 49:505-523. [PMID: 33641651 DOI: 10.1142/s0192415x21500233] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Triple-negative breast cancer (TNBC) is the subtype of breast cancer with more aggressive growth and metastasis and without efficient therapies. Hence, it is worthwhile to search for potential effective drug candidates. According to our previous study, isoliquiritigenin (ISL) exerted a potent anticancer effect on breast cancer proliferation. Its effect on TNBC growth, metastasis and mechanism deserves further investigation. In this study, PCR array screened a significant increase of miR-200c in BT-549 and MDA-MB-231 cells after ISL treatment, and ISH exerted that miR-200c was expressed at a low level in breast cancer tissue of patients. We also found that ISL could up-regulate miR-200c, resulting in the inhibition of epithelial-mesenchymal transition. Meanwhile, ISL could inhibit metastasis and tumor growth in nude mice models through the increase of miR-200c. Further study displayed that ISL decreased c-Jun expression through the increase of miR-200c. Interestingly, we also detected that ISL might increase miR-200c expression through the demethylation of miR-200c promoter region. These findings indicated that ISL could be potentially developed as a novel drug candidate for TNBC in microRNA-based cancer therapies.
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Affiliation(s)
- Fu Peng
- School of Chinese Medicine, The University of Hong Kong, Hong Kong
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional, Chinese Medicine, Chengdu, P. R. China
- West China School of Pharmacy, Sichuan University, Chengdu, P. R. China
| | - Hailin Tang
- School of Chinese Medicine, The University of Hong Kong, Hong Kong
- Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China
| | - Junrong Du
- West China School of Pharmacy, Sichuan University, Chengdu, P. R. China
| | - Jianping Chen
- School of Chinese Medicine, The University of Hong Kong, Hong Kong
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional, Chinese Medicine, Chengdu, P. R. China
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34
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Role of Actin Cytoskeleton in E-cadherin-Based Cell–Cell Adhesion Assembly and Maintenance. J Indian Inst Sci 2021. [DOI: 10.1007/s41745-020-00214-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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35
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Lippert AH, Dimov IB, Winkel AK, Humphrey J, McColl J, Chen KY, Santos AM, Jenkins E, Franze K, Davis SJ, Klenerman D. Soft Polydimethylsiloxane-Supported Lipid Bilayers for Studying T Cell Interactions. Biophys J 2021; 120:35-45. [PMID: 33248128 PMCID: PMC7820804 DOI: 10.1016/j.bpj.2020.11.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 09/22/2020] [Accepted: 11/17/2020] [Indexed: 12/23/2022] Open
Abstract
Much of what we know about the early stages of T cell activation has been obtained from studies of T cells interacting with glass-supported lipid bilayers that favor imaging but are orders of magnitude stiffer than typical cells. We developed a method for attaching lipid bilayers to polydimethylsiloxane polymer supports, producing "soft bilayers" with physiological levels of mechanical resistance (Young's modulus of 4 kPa). Comparisons of T cell behavior on soft and glass-supported bilayers revealed that whereas late stages of T cell activation are thought to be substrate-stiffness dependent, early calcium signaling was unaffected by substrate rigidity, implying that early steps in T cell receptor triggering are not mechanosensitive. The exclusion of large receptor-type phosphatases was observed on the soft bilayers, however, even though it is yet to be demonstrated at authentic cell-cell contacts. This work sets the stage for an imaging-based exploration of receptor signaling under conditions closely mimicking physiological cell-cell contact.
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Affiliation(s)
- Anna H Lippert
- Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
| | - Ivan B Dimov
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
| | - Alexander K Winkel
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
| | - Jane Humphrey
- Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
| | - James McColl
- Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
| | - Kevin Y Chen
- Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
| | - Ana M Santos
- Radcliffe Department of Medicine and MRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Edward Jenkins
- Radcliffe Department of Medicine and MRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Kristian Franze
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
| | - Simon J Davis
- Radcliffe Department of Medicine and MRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - David Klenerman
- Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
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36
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Beauséjour M, Boutin A, Vachon PH. Anoikis and the Human Gut Epithelium in Health and Disease. ANOIKIS 2021:95-126. [DOI: 10.1007/978-3-030-73856-3_5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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37
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Zhang J, Zhang Y, Cheng S, Mu Y, Liu Y, Yi X, Jiang D, Ding Y, Zhuang R. LAIR-1 overexpression inhibits epithelial-mesenchymal transition in osteosarcoma via GLUT1-related energy metabolism. World J Surg Oncol 2020; 18:136. [PMID: 32563267 PMCID: PMC7345510 DOI: 10.1186/s12957-020-01896-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 05/28/2020] [Indexed: 02/07/2023] Open
Abstract
Background Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor belonging to the immunoglobulin superfamily. Although previous studies have evaluated the biological role of LAIR in solid tumors, the precise mechanisms underlying the functions of LAIR-1 as a regulator of tumor biological functions remain unclear. Methods LAIR-1 expression was evaluated by immunohistochemical analysis using an osteosarcoma (OS) tissue microarray. Wound healing and transwell migration assays were performed to evaluate tumor cell migration. Quantitative real-time polymerase chain reaction (qPCR) and western blotting were conducted to detect the expression of epithelial–mesenchymal transition (EMT)-related molecules. RNA-sequencing (RNA-seq) was conducted to evaluate the mRNA expression profiles after overexpressing LAIR-1 in OS cells. Glucose transporter (Glut)1 expression in OS cells was evaluated by western blotting. Results LAIR-1 expression was significantly different between the T1 and T2 stages of OS tumors, and it inhibited OS cell migration. LAIR-1 expression was inversely correlated with the expression of Twist1, an EMT-associated transcription factor, via the Forkhead box O1 signal transduction pathway. Furthermore, RNA-seq and qPCR demonstrated that the expression of EMT energy metabolism-related molecules was significantly reduced after LAIR-1 overexpression. Conclusions LAIR-1 overexpression decreased the expression of Glut1 and inhibited the expression of EMT-related molecules in OS cells. These findings provide new insights into the molecular mechanism underlying OS progression.
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Affiliation(s)
- Jinxue Zhang
- Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, #1 Xinsi Road, Xi'an, 710032, China.,Department of Immunology, Fourth Military Medical University, #129 West Changle Road, Xi'an, 710032, China
| | - Yuan Zhang
- Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, 710072, Shaanxi, China
| | - Shiyang Cheng
- Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, #1 Xinsi Road, Xi'an, 710032, China
| | - Yang Mu
- Department of Immunology, Fourth Military Medical University, #129 West Changle Road, Xi'an, 710032, China
| | - Yongming Liu
- Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, #1 Xinsi Road, Xi'an, 710032, China
| | - Xin Yi
- Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, #1 Xinsi Road, Xi'an, 710032, China
| | - Dongxu Jiang
- Department of Immunology, Fourth Military Medical University, #129 West Changle Road, Xi'an, 710032, China
| | - Yong Ding
- Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, #1 Xinsi Road, Xi'an, 710032, China.
| | - Ran Zhuang
- Department of Immunology, Fourth Military Medical University, #129 West Changle Road, Xi'an, 710032, China.
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