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Dong XM, Chen L, Xu YX, Wu P, Xie T, Liu ZQ. Exploring metabolic reprogramming in esophageal cancer: the role of key enzymes in glucose, amino acid, and nucleotide pathways and targeted therapies. Cancer Gene Ther 2025; 32:165-183. [PMID: 39794467 DOI: 10.1038/s41417-024-00858-5] [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: 10/18/2024] [Revised: 11/08/2024] [Accepted: 11/14/2024] [Indexed: 01/13/2025]
Abstract
Esophageal cancer (EC) is one of the most common malignancies worldwide with the character of poor prognosis and high mortality. Despite significant advancements have been achieved in elucidating the molecular mechanisms of EC, for example, in the discovery of new biomarkers and metabolic pathways, effective treatment options for patients with advanced EC are still limited. Metabolic heterogeneity in EC is a critical factor contributing to poor clinical outcomes. This heterogeneity arises from the complex interplay between the tumor microenvironment and genetic factors of tumor cells, which drives significant metabolic alterations in EC, a process known as metabolic reprogramming. Understanding the mechanisms of metabolic reprogramming is essential for developing new antitumor therapies and improving treatment outcomes. Targeting the distinct metabolic alterations in EC could enable more precise and effective therapies. In this review, we explore the complex metabolic changes in glucose, amino acid, and nucleotide metabolism during the progression of EC, and how these changes drive unique nutritional demands in cancer cells. We also evaluate potential therapies targeting key metabolic enzymes and their clinical applicability. Our work will contribute to enhancing knowledge of metabolic reprogramming in EC and provide new insights and approaches for the clinical treatment of EC.
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Affiliation(s)
- Xue-Man Dong
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
| | - Lin Chen
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
| | - Yu-Xin Xu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
| | - Pu Wu
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China
| | - Tian Xie
- School of Pharmacy, Hangzhou Normal University, Hangzhou, China.
| | - Zhao-Qian Liu
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
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2
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Wang M, Zhang H, Lu Z, Su W, Tan Y, Wang J, Jia X. PSAT1 mediated EMT of colorectal cancer cells by regulating Pl3K/AKT signaling pathway. J Cancer 2024; 15:3183-3198. [PMID: 38706897 PMCID: PMC11064270 DOI: 10.7150/jca.93789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 03/09/2024] [Indexed: 05/07/2024] Open
Abstract
Background: The metastasis of colorectal cancer (CRC) is one of the significant barriers impeding its treated consequence and bring about high mortality, less surgical resection rate and poor prognosis of CRC patients. PSAT1 is an enzyme involved in serine biosynthesis. The studies showed that PSAT1 plays the part of a crucial character in the regulation of tumor metastasis. And Epithelial-Mesenchymal Transition (EMT) is a process of cell reprogramming in which epithelialcells obtain mesenchymal phenotypes. It is a crucial course in promoting cell metastasis and the progression of malignant tumors. The relationship between PSAT1 and EMT in colorectal cancer, as well as the underlying molecular mechanisms, remains enigmatic and warrants thorough exploration. These findings suggest that PSAT1 may serve as a promising therapeutic target for mitigating colorectal cancer metastasis and holds the potential to emerge as a valuable prognostic biomarker in forthcoming research endeavors. Materials and Methods: Utilizing TCGA dataset in conjunction with clinical CRC specimens, our initial focus was directed towards an in-depth examination of PSAT1 expression within CRC, specifically exploring its potential correlation with the adverse prognostic outcomes experienced by patients. Furthermore, we conducted a comprehensive investigation into the regulatory influence exerted by PSAT1 on CRC through the utilization of siRNA knockdown techniques. In the realm of in vitro experimentation, we meticulously evaluated the impact of PSAT1 on various facets of CRC progression, including cell migration, invasion, proliferation, and colony formation. In order to elucidate the intricate effects in question, we adopted a multifaceted methodology that encompassed a range of assays and analyses. These included wound healing assays, transwell assays, utilization of the Cell Counting Kit-8 (CCK-8) assay, and colony formation assays. By employing this diverse array of investigative techniques, we were able to achieve a comprehensive comprehension of the multifaceted role that PSAT1 plays in the pathogenesis of colorectal cancer. This multifarious analysis greatly contributed to our in-depth understanding of the complex mechanisms at play in colorectal cancer pathogenesis. Using WB and PCR experiments, we found that PSAT1 has a role in regulating EMT development in CRC.In terms of mechanism, we found that PSAT1 affected EMT by Regulating Pl3K/AKT Signaling Pathway. Results: Our investigation revealed a noteworthy down-regulation of PSAT1 expression in CRC specimens. Importantly, this down-regulation exhibited a significant positive correlation with the unfavorable prognosis of patients afflicted with CRC. Functionally, our study showcased that the siRNA-mediated knockdown of PSAT1 markedly enhanced various key aspects of CRC pathogenesis in an in vitro setting. Specifically, this included a substantial promotion of CRC cell migration, invasion, proliferation, and colony formation. Moreover, the silencing of PSAT1 also demonstrated a substantial promotion of the EMT process. Intriguingly, our research unveiled a hitherto unexplored mechanism underlying the regulatory role of PSAT1 in CRC and EMT. We have established, for the first time, that PSAT1 exerts its influence by modulating the activation of the PI3K/AKT Signaling Pathway. This mechanistic insight provides a valuable contribution to the understanding of the molecular underpinnings of CRC progression and EMT induction mediated by PSAT1. Conclusions: In unison, our research findings shed light on the previously uncharted and significant role of the PSAT1/PI3K/AKT axis in the initiation of the EMT process in CRC. Furthermore, our discoveries introduce a novel biomarker with potential implications for the clinical diagnosis and treatment of CRC.
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Affiliation(s)
- Mingjin Wang
- School of Pharmacy, Anhui University of Traditional Chinese Medicine, 230012 Hefei, Anhui, China
- The Key Laboratory of Hepatobiliary Pancreas, Southern District, Anhui Provincial Hospital, The First Affliated Hosnital of USTC, University of Science and Technology of China, 230022 Hefei, Anhui, China
| | - Houshun Zhang
- Department of Pathology, Anhui Provincial Hospital, The First Affliated Hosnital of USTC, University of Science and Technology of China, 230002 Hefei, Anhui, China
| | - Zhiyuan Lu
- School of Pharmacy, Anhui University of Traditional Chinese Medicine, 230012 Hefei, Anhui, China
| | - Wenrui Su
- School of Pharmacy, Anhui University of Traditional Chinese Medicine, 230012 Hefei, Anhui, China
| | - Yanan Tan
- School of Pharmacy, Anhui University of Traditional Chinese Medicine, 230012 Hefei, Anhui, China
| | - Jiayu Wang
- School of Pharmacy, Anhui University of Traditional Chinese Medicine, 230012 Hefei, Anhui, China
| | - Xiaoyi Jia
- School of Pharmacy, Anhui University of Traditional Chinese Medicine, 230012 Hefei, Anhui, China
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3
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Wei QY, Jin F, Wang ZY, Li BJ, Cao WB, Sun ZY, Mo SJ. MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:1497-1523. [PMID: 38617454 PMCID: PMC11008420 DOI: 10.3748/wjg.v30.i11.1497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/12/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.
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Affiliation(s)
- Qi-Ying Wei
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Feng Jin
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhong-Yu Wang
- Department of Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Bing-Jie Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Wen-Bo Cao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhi-Yan Sun
- Division of Special Service, Department of Basic Oncology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sai-Jun Mo
- Department of Basic Science of Oncology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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4
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Doghish AS, El-Husseiny AA, Abdelmaksoud NM, El-Mahdy HA, Elsakka EGE, Abdel Mageed SS, Mahmoud AMA, Raouf AA, Elballal MS, El-Dakroury WA, AbdelRazek MMM, Noshy M, El-Husseiny HM, Abulsoud AI. The interplay of signaling pathways and miRNAs in the pathogenesis and targeted therapy of esophageal cancer. Pathol Res Pract 2023; 246:154529. [PMID: 37196470 DOI: 10.1016/j.prp.2023.154529] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/19/2023]
Abstract
Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-β signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Ahmed A El-Husseiny
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Cairo, Egypt
| | - Nourhan M Abdelmaksoud
- Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Abdulla M A Mahmoud
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Amr Raouf
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohamed M M AbdelRazek
- Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mina Noshy
- Clinical Pharmacy Department, Faculty of Pharmacy, King Salman International University (KSIU), SouthSinai, Ras Sudr 46612, Egypt
| | - Hussein M El-Husseiny
- Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan; Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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5
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Sun W, Liu R, Gao X, Lin Z, Tang H, Cui H, Zhao E. Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers. Biomark Res 2023; 11:48. [PMID: 37147729 PMCID: PMC10161514 DOI: 10.1186/s40364-023-00487-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 04/15/2023] [Indexed: 05/07/2023] Open
Abstract
The serine-glycine-one-carbon (SGOC) metabolic pathway is critical for DNA methylation, histone methylation, and redox homeostasis, in addition to protein, lipid, and nucleotide biosynthesis. The SGOC pathway is a crucial metabolic network in tumorigenesis, wherein the outputs are required for cell survival and proliferation and are particularly likely to be co-opted by aggressive cancers. SGOC metabolism provides an integration point in cell metabolism and is of crucial clinical significance. The mechanism of how this network is regulated is the key to understanding tumor heterogeneity and overcoming the potential mechanism of tumor recurrence. Herein, we review the role of SGOC metabolism in cancer by focusing on key enzymes with tumor-promoting functions and important products with physiological significance in tumorigenesis. In addition, we introduce the ways in which cancer cells acquire and use one-carbon unit, and discuss the recently clarified role of SGOC metabolic enzymes in tumorigenesis and development, as well as their relationship with cancer immunotherapy and ferroptosis. The targeting of SGOC metabolism may be a potential therapeutic strategy to improve clinical outcomes in cancers.
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Affiliation(s)
- Wei Sun
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, No.2 Tiansheng Road, Beibei District, 400716, Chongqing, China
- Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China
- Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400715, China
| | - Ruochen Liu
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, No.2 Tiansheng Road, Beibei District, 400716, Chongqing, China
- Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China
- Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400715, China
- Jinfeng Laboratory, Chongqing, 401329, China
| | - Xinyue Gao
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, No.2 Tiansheng Road, Beibei District, 400716, Chongqing, China
| | - Zini Lin
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, No.2 Tiansheng Road, Beibei District, 400716, Chongqing, China
| | - Hongao Tang
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, No.2 Tiansheng Road, Beibei District, 400716, Chongqing, China
| | - Hongjuan Cui
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, No.2 Tiansheng Road, Beibei District, 400716, Chongqing, China.
- Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China.
- Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400715, China.
- Jinfeng Laboratory, Chongqing, 401329, China.
| | - Erhu Zhao
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, No.2 Tiansheng Road, Beibei District, 400716, Chongqing, China.
- Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China.
- Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400715, China.
- Jinfeng Laboratory, Chongqing, 401329, China.
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6
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Chen J, Ye C, Yang Z, Zhang C, Li P, Xu B, Wu A, Zhang X, Xue X. Erchen decoction to reduce oxidative stress in dyslipidemia phlegm-dampness retention syndrome mice: In vivo mechanism revealed by metabolomics (liquid chromatography-mass spectrometry). PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 115:154808. [PMID: 37087794 DOI: 10.1016/j.phymed.2023.154808] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/25/2023] [Accepted: 04/04/2023] [Indexed: 05/03/2023]
Abstract
OBJECTIVE Erchen decoction, a traditional Chinese medicine formula, can reduce the level of oxidative stress for the treatment of dyslipidemia phlegm-dampness retention syndrome (DPDRS); however, studies have not elucidated the mechanism underlying its metabolic action. Here, liquid chromatography-mass spectrometry (LC-MS)-based metabolomic techniques were utilized to characterize the in vivo effects of Erchen decoction in achieving reduction of oxidative stress levels and understand the potential metabolic mechanisms of action. METHODS We constructed a DPDRS animal model using a multifactorial composite modeling approach, and Erchen decoction was administered by gavage. We employed LC-MS-based metabolomic techniques in combination with serum-associated factors, gene transcription, methylation detection, and hematoxylin and eosin staining. RESULTS In this study, the constructed animal model of DPDRS had satisfactory quality. Erchen decoction treatment reduced the levels of low-density lipoprotein cholesterol, t total cholesterol and riglyceride; it improved the endothelial structure, increased levels of serum β-nicotinamide adenine dinucleotide phosphate and glutathione concentrations, increased aortic phosphoserine aminotransferase and phosphoserine phosphatase gene expression levels, and decreased aortic phosphoglycerate dehydrogenase methylation level. A total of 64 differential metabolites were obtained using LC-MS assay, and 34 differential metabolic pathways were obtained after enrichment. CONCLUSIONS Erchen decoction treatment of DPDRS mice reversed lipid indexes, improved vascular endothelial structure, increased serum and aortic anti-oxidative stress factor concentration and expression levels, and decreased methylation levels, thereby reducing oxidative stress and protecting vascular endothelium. Tricarboxylic acid cycle and metabolic pathways of serum glutamine, serine, tryptophan, pyrimidine, and pyruvate were the most relevant metabolic pathways involved in reducing oxidative stress levels by Erchen decoction during DPDRS treatment; especially, mitochondrial redox homeostasis maintenance in endothelial cells may be crucial. In this work, the therapeutic potential of Erchen decoction for reducing the oxidative stress level in DPDRS was demonstrated; however, its in-depth mechanism is worth further exploration.
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Affiliation(s)
- Jing Chen
- Preventive Treatment of Disease Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chao Ye
- Orthopedics Department, Dongzhimen Hospital, Beijing University of Chinese edicine, Beijing 100700, China
| | - Zheng Yang
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Cixiong Zhang
- State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China
| | - Pengyang Li
- Orthopedics Department, Dongzhimen Hospital, Beijing University of Chinese edicine, Beijing 100700, China
| | - Bing Xu
- Traditional Chinese Medicine Department, Tibetology Research Center of Beijing Tibetan Medicine Hospital, Beijing 100029, China
| | - Aiming Wu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xiaodong Zhang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xiaolin Xue
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100700, China.
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Iacob R, Mandea M, Iacob S, Pietrosanu C, Paul D, Hainarosie R, Gheorghe C. Liquid Biopsy in Squamous Cell Carcinoma of the Esophagus and of the Head and Neck. Front Med (Lausanne) 2022; 9:827297. [PMID: 35572996 PMCID: PMC9098838 DOI: 10.3389/fmed.2022.827297] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/15/2022] [Indexed: 11/13/2022] Open
Abstract
Squamous cell carcinomas of the esophagus (ESCC) and of the head and neck (HNSCC) are two neoplasms that share common risk factors and have the same embryological origin, but a very different prognosis, the 5-year survival of HNSCC being almost double (40–50%) compared to the 5-year survival of ESCC (20%). Current guidelines emphasize the importance of screening for ESCC in patients diagnosed with head and neck cancers. A liquid biopsy is a novel tool for diagnosis, prognostic stratification, and personalized therapy. Liquid biopsy biomarkers for these two malignancies could help both their early detection, facilitate residual disease identification, and provide prognosis information. The present systematic review of the literature was aimed at describing the liquid biopsy biomarkers present in these two malignancies, with an emphasis on potential clinical applications.
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Affiliation(s)
- Razvan Iacob
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Matei Mandea
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
| | - Speranta Iacob
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Catalina Pietrosanu
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Professor Doctor Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania
| | - Doru Paul
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, United States
| | - Razvan Hainarosie
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Professor Doctor Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania
- *Correspondence: Razvan Hainarosie
| | - Cristian Gheorghe
- University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
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8
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Elevation of microRNA-365 impedes malignant behaviors of gastric cancer cells by inhibiting PAX6. Funct Integr Genomics 2022; 22:825-834. [PMID: 35484308 DOI: 10.1007/s10142-022-00858-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 04/02/2022] [Accepted: 04/04/2022] [Indexed: 11/04/2022]
Abstract
MicroRNA-365 (miR-365) has been revealed to be a vital regulator in tumorigenesis of multiple cancers, while there is a large gap in the knowledge about miR-365 expression and gastric cancer (GC). This research focused on the effects of miR-365 and paired box 6 (PAX6) on GC development. Levels of miR-365 and PAX6 in GC tissues and cell lines were determined, followed by the screening of the AGS and NCI-N87 cells. Gain- or loss-of-function assays were used to analyze the effect of miR-365, PAX6 on AGS and NCI-N87 cell behaviors. The effects of altered miR-365 and PAX6 on animal models were observed. Moreover, to assess the interaction between miR-365 and PAX6, we implemented the bioinformatic method and dual luciferase reporter gene assay. MiR-365 was decreased while PAX6 was increased in GC tissues and cell lines. There existed a negative association between miR-365 and PAX6. The promoted miR-365 could repress oncogenicity in vivo and malignant transformation in vitro of GC. PAX6 was the target gene of miR-365. Overexpression of PAX6 reversed the inhibitory effect of up-regulated miR-365 on malignant behavior of gastric cancer cells. Our research displays that the amplification of miR-365 could suppress the malignant behaviors of GC cells via inhibiting PAX6, which may be helpful for GC treatment.
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9
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Weidle UH, Nopora A. MicroRNAs and Corresponding Targets in Esophageal Cancer as Shown In Vitro and In Vivo in Preclinical Models. Cancer Genomics Proteomics 2022; 19:113-129. [PMID: 35181582 DOI: 10.21873/cgp.20308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/17/2022] [Accepted: 01/19/2022] [Indexed: 02/08/2023] Open
Abstract
Squamous cell carcinoma of the esophagus is associated with a dismal prognosis. Therefore, identification of new targets and implementation of new treatment modalities are issues of paramount importance. Based on a survey of the literature, we identified microRNAs conferring antitumoral activity in preclinical in vivo experiments. In the category of miRs targeting secreted factors and transmembrane receptors, four miRs were up-regulated and 10 were down-regulated compared with five out of nine in the category transcription factors, and six miRs were down-regulated in the category enzymes, including metabolic enzymes. The down-regulated miRs have targets which can be inhibited by small molecules or antibody-related entities, or re-expressed by reconstitution therapy. Up-regulated miRs have targets which can be reconstituted with small molecules or inhibited with antagomirs.
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Affiliation(s)
- Ulrich H Weidle
- Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
| | - Adam Nopora
- Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
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10
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Chidamide and Radiotherapy Synergistically Induce Cell Apoptosis and Suppress Tumor Growth and Cancer Stemness by Regulating the MiR-375-EIF4G3 Axis in Lung Squamous Cell Carcinomas. JOURNAL OF ONCOLOGY 2021; 2021:4936207. [PMID: 34194495 PMCID: PMC8214506 DOI: 10.1155/2021/4936207] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 05/16/2021] [Indexed: 11/24/2022]
Abstract
As a selective histone deacetylase (HDAC) inhibitor developed in China, chidamide has been applied for the treatment of refractory peripheral T-cell lymphoma (PTCL) and multiple solid tumors, including lung cancer. However, the underlying mechanisms are not well elucidated. In our present study, we found that chidamide and radiation acted synergistically to suppress cell and xenograft growth of lung squamous cell carcinoma cells by inducing cell apoptosis. Moreover, chidamide alone or a combination of chidamide and radiation treatment inhibited cancer cell stemness. miRNA microarray analysis demonstrated that miR-375 was the highest upregulated microRNA (miRNA) in NCI-2170 and NCI-H226 cells treated with chidamide alone or treated with chidamide plus radiation, compared with normal control. Inhibition of miR-375 attenuated the promoting effect of chidamide alone and chidamide plus radiation-induced NCI-2170 and NCI-H226 cell apoptosis and reverted the suppression of cancer stemness caused by chidamide alone or chidamide plus radiation treatment. Moreover, EIF4G3, a scaffold protein in the translation initiation complex, was found to be a direct target of miR-375 based on the luciferase reporter assay and western blot analysis. Interestingly, both chidamide alone and chidamide plus radiation treatments suppressed the mRNA and protein expression of EIF4G3. Silence of EIF4G3 also induced cell apoptosis and suppressed tumor growth in NCI-2170 and NCI-H226 cells. These data suggest that chidamide shows a synergistic effect with radiation therapy on lung squamous cell carcinomas by modulating the miR-375-EIF4G3 axis, which may afford an effective strategy to overcome the drug resistance of chidamide in clinical cancer therapy.
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Liu Y, Jia J, Song B, Qiu H, Liang G, Zhang B, Wang K. Serum microRNA-365 suppresses non-small-cell lung cancer metastasis and invasion in patients with bone metastasis of lung cancer. J Int Med Res 2021; 48:300060520939718. [PMID: 33121309 PMCID: PMC7604948 DOI: 10.1177/0300060520939718] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Objective In the present investigation, we evaluated the effects of microRNA-365 (miR-365) on non-small-cell lung cancer (NSCLC) cell metastasis and invasion in patients with bone metastasis of lung cancer. Methods Blood samples from patients with NSCLC and healthy controls and the A549 adenocarcinoma cell line were included in this study. Quantitative real-time PCR and microarray were performed on blood samples. The MTT assay, luciferase reporter assay, Transwell assay, ELISA, and western blot were performed to evaluate expression of associated factors. Results Expression of miR-365 was reduced in patients with bone metastasis of NSCLC. Downregulation of miR-365 promoted cell growth, metastasis, and invasion of NSCLC. Upregulation of miR-365 reduced cell growth, metastasis, and invasion of NSCLC. Downregulation of miR-365 induced expression of NKX homeobox-1 (NKX2-1), epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase (PI3K), and p-Akt proteins in an in vitro model of NSCLC. Inhibition of NKX2-1 reduced the effects of miR-365 on cell growth, metastasis, and invasion of NSCLC. Activation of EGFR reduced the effects of miR-365 on cell growth, metastasis, and invasion of NSCLC. Conclusions The study established that the serum miR-365 suppresses NSCLC cell metastasis and invasion in patients with bone metastasis of lung cancer via EGFR/PI3K through NKX2-1.
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Affiliation(s)
- Yanyan Liu
- Department of Oncology, The First Clinical Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Junmei Jia
- Department of Oncology, The First Clinical Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Bin Song
- Department of Oncology, The First Clinical Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Haile Qiu
- Department of Oncology, The First Clinical Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Gang Liang
- Department of Pathology, The First Clinical Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Bo Zhang
- Department of Breast Diseases, Shanxi Cancer Hospital, Taiyuan, Shanxi, China
| | - Kang Wang
- Department of Oncology, The First Clinical Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
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ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4. Biosci Rep 2021; 40:222148. [PMID: 32065218 PMCID: PMC7133517 DOI: 10.1042/bsr20194352] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 02/04/2020] [Accepted: 02/05/2020] [Indexed: 12/13/2022] Open
Abstract
Emerging evidence has confirmed that long noncoding RNAs (lncRNAs) are strongly involved in tumor initiation and development. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) has been identified as a tumor facilitator in some cancers; nevertheless, its functional significance and regulatory mechanism remain greatly unclear in esophageal squamous cell carcinoma (ESCC). Here, we detected ZFPM2-AS1 expression in ESCC cell lines using qRT-PCR. ZFPM2-AS1 knockdown models were established for investigating the biological function of ZFPM2-AS1 in ESCC cells. The association between miR-3612 and ZFPM2-AS1 or TRAF4 was assessed by RNA pull-down and luciferase reporter assays. The present study indicated that ZFPM2-AS1 was significantly up-regulated in ESCC cells. Functional assays manifested that ZFPM2-AS1 knockdown restrained cell proliferation, migration and invasion, and facilitated cell apoptosis in ESCC. Mechanistically, ZFPM2-AS1 promoted ESCC cell growth and up-regulated TRAF4 to trigger NF-κB pathway by sequestering miR-3612. Besides, miR-3612 was confirmed to be a tumor inhibitor in ESCC. Through restoration experiments, we observed that TRAF4 overexpression could recover the suppressive effect of ZFPM2-AS1 on ESCC cell growth. Collectively, all the results suggested that ZFPM2-AS1 was an oncogene in ESCC cell growth by up-regulating TRAF4 and activating NF-κB pathway.
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Metcalf S, Petri BJ, Kruer T, Green B, Dougherty S, Wittliff JL, Klinge CM, Clem BF. Serine synthesis influences tamoxifen response in ER+ human breast carcinoma. Endocr Relat Cancer 2021; 28:27-37. [PMID: 33112838 PMCID: PMC7780089 DOI: 10.1530/erc-19-0510] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 10/20/2020] [Indexed: 12/24/2022]
Abstract
Estrogen receptor-positive breast cancer (ER+ BC) is the most common form of breast carcinoma accounting for approximately 70% of all diagnoses. Although ER-targeted therapies have improved survival outcomes for this BC subtype, a significant proportion of patients will ultimately develop resistance to these clinical interventions, resulting in disease recurrence. Phosphoserine aminotransferase 1 (PSAT1), an enzyme within the serine synthetic pathway (SSP), has been previously implicated in endocrine resistance. Therefore, we determined whether expression of SSP enzymes, PSAT1 or phosphoglycerate dehydrogenase (PHGDH), affects the response of ER+ BC to 4-hydroxytamoxifen (4-OHT) treatment. To investigate a clinical correlation between PSAT1, PHGDH, and endocrine resistance, we examined microarray data from ER+ patients who received tamoxifen as the sole endocrine therapy. We confirmed that higher PSAT1 and PHGDH expression correlates negatively with poorer outcomes in tamoxifen-treated ER+ BC patients. Next, we found that SSP enzyme expression and serine synthesis were elevated in tamoxifen-resistant compared to tamoxifen-sensitive ER+ BC cells in vitro. To determine relevance to endocrine sensitivity, we modified the expression of either PSAT1 or PHGDH in each cell type. Overexpression of PSAT1 in tamoxifen-sensitive MCF-7 cells diminished 4-OHT inhibition on cell proliferation. Conversely, silencing of either PSAT1 or PHGDH resulted in greater sensitivity to 4-OHT treatment in LCC9 tamoxifen-resistant cells. Likewise, the combination of a PHGDH inhibitor with 4-OHT decreased LCC9 cell proliferation. Collectively, these results suggest that overexpression of serine synthetic pathway enzymes contribute to tamoxifen resistance in ER+ BC, which can be targeted as a novel combinatorial treatment option.
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Affiliation(s)
- Stephanie Metcalf
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
| | - Belinda J. Petri
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
| | - Traci Kruer
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
| | - Benjamin Green
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
| | - Susan Dougherty
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
| | - James L. Wittliff
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
| | - Carolyn M. Klinge
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
- James Graham Brown Cancer Center, University of Louisville,
Louisville, KY, USA
| | - Brian F. Clem
- Department of Biochemistry and Molecular Genetics,
University of Louisville, Louisville, KY, USA
- James Graham Brown Cancer Center, University of Louisville,
Louisville, KY, USA
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Li MK, Liu LX, Zhang WY, Zhan HL, Chen RP, Feng JL, Wu LF. Long non‑coding RNA MEG3 suppresses epithelial‑to‑mesenchymal transition by inhibiting the PSAT1‑dependent GSK‑3β/Snail signaling pathway in esophageal squamous cell carcinoma. Oncol Rep 2020; 44:2130-2142. [PMID: 32901893 PMCID: PMC7550985 DOI: 10.3892/or.2020.7754] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 07/29/2020] [Indexed: 02/07/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer in China, and the prognosis of patients remains poor mainly due to the occurrence of lymph node and distant metastasis. The long non‑coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been shown to have tumor‑suppressive properties and to play an important role in epithelial‑to‑mesenchymal transition (EMT) in some solid tumors. However, whether MEG3 is involved in EMT in ESCC remains unclear. In the present study, the MEG3 expression level and its association with tumorigenesis were determined in 43 tumor tissues of patients with ESCC and in ESCC cells using reverse transcription‑quantitative PCR analysis. Gene microarray analysis was performed to detect differentially expressed genes (DEGs). Based on the functional annotation results, the effects of ectopic expression of MEG3 on cell growth, migration, invasion and EMT were assessed. MEG3 expression level was found to be markedly lower in tumor tissues and cells. Statistical analysis revealed that MEG3 expression was significantly negatively associated with lymph node metastasis and TNM stage in ESCC. Fluorescence in situ hybridization assay demonstrated that MEG3 was expressed mainly in the nucleus. Ectopic expression of MEG3 inhibited cell proliferation, migration, invasion and cell cycle progression in EC109 cells. Gene microarray results demonstrated that 177 genes were differentially expressed ≥2.0 fold in MEG3‑overexpressing cells, including 23 upregulated and 154 downregulated genes. Functional annotation revealed that the DEGs were mainly involved in amino acid biosynthetic process, mitogen‑activated protein kinase signaling, and serine and glycine metabolism. Further experiments indicated that the ectopic expression of MEG3 significantly suppressed cell proliferation, migration, invasion and EMT by downregulating phosphoserine aminotransferase 1 (PSAT1). In pathological tissues, PSAT1 and MEG3 were significantly negatively correlated, and high expression of PSAT1 predicted poor survival. Taken together, these results suggest that MEG3 may be a useful prognostic biomarker and may suppress EMT by inhibiting the PSAT1‑dependent glycogen synthase kinase‑3β/Snail signaling pathway in ESCC.
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Affiliation(s)
- Ming-Kai Li
- Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - Li-Xuan Liu
- Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - Wei-Yi Zhang
- Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - Hao-Lian Zhan
- Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - Rui-Pei Chen
- Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - Jia-Lin Feng
- Department of Information, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - Ling-Fei Wu
- Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
- Correspondence to: Professor Ling-Fei Wu, Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, 69 Dongxia Road, Shantou, Guangdong 515041, P.R. China, E-mail:
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Jia Q, Yan S, Huang J, Xu S. Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway. NANOSCALE RESEARCH LETTERS 2020; 15:177. [PMID: 32902711 PMCID: PMC7479668 DOI: 10.1186/s11671-020-03396-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 08/03/2020] [Indexed: 06/11/2023]
Abstract
It is unclear about the functional role of microRNA-133a-3p (miR-133a-3p) in intracranial aneurysm (IA). Hence, the aim of the present study was to investigate the regulatory role of miR-133a-3p on the regulation of vascular endothelial injury-induced IA through phosphoserine aminotransferase 1 (PSAT1)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway. Normal intracranial arteriole tissues and IA tissues were gathered from patients with brain trauma and IA. The expression of miR-133a-3p, PSAT1, GSK3β, and β-catenin in tissues was determined by RT-qPCR and western blot analysis. The endothelial cells (ECs) of the human IA were cultured and treated with miR-133a-3p mimic and si-PSAT1 to determine their functions in endothelial cell migration, apoptosis, and proliferation. The expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, Ki-67, CyclinD1, Bax, and Bcl-2 in ECs were tested by RT-qPCR or western blot analysis. Moreover, IA rat model was established to detect the pathological changes and the expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, VEGF, and MMP-9 in IA tissues in vivo. Expression of miR-133a-3p was related to the number and size of IA. MiR-133a-3p expression was deceased and the PSAT1, GSK3β, and β-catenin expression was raised in IA. Restored miR-133a-3p and depleted PSAT1 alleviated the pathological change; reduced PSAT1, GSK3β, and β-catenin expression in IA; suppressed apoptosis and advanced proliferation and migration of IA ECs, as well as reduced VEGF and MMP-9 expression in IA tissues in vivo. Our study suggests that overexpression of miR-133a-3p or downregulation of PSAT1 restrains endothelial cell damage and advances endothelial cell proliferation via inhibiting the GSK3β/β-catenin pathway in IA. MiR-133a-3p might be a potential candidate marker and therapeutic target for IA.
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Affiliation(s)
- Qiang Jia
- Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300050, Tianjin, China
| | - Shixin Yan
- Department of Radiology, Tianjin Huanhu Hospital, Tianjin, 300050, Tianjin, China
| | - Jie Huang
- Department of Neurology, Cangzhou People's Hospital, 20 North Street, Cangzhou, 061000, Hebei, China.
| | - Shixin Xu
- Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An shan xin Road, Nan Kai District, Tianjin, 300000, Tianjin, China.
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Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2019; 21:ijms21010258. [PMID: 31905958 PMCID: PMC6982002 DOI: 10.3390/ijms21010258] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/04/2019] [Accepted: 12/14/2019] [Indexed: 12/14/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.
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Song H, Song J, Lu L, Li S. SNHG8 is upregulated in esophageal squamous cell carcinoma and directly sponges microRNA-411 to increase oncogenicity by upregulating KPNA2. Onco Targets Ther 2019; 12:6991-7004. [PMID: 31695414 PMCID: PMC6717851 DOI: 10.2147/ott.s214881] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 08/10/2019] [Indexed: 12/22/2022] Open
Abstract
Background The long noncoding RNA, small nucleolar RNA host gene 8 (SNHG8), is upregulated in multiple human cancer types. However, whether SNHG8 is aberrantly expressed in esophageal squamous cell carcinoma (ESCC) and its biological functions have yet to be elucidated. Thus, we aimed to determine the expression status of SNHG8 in ESCC, explore the effects of SNHG8 on the oncogenicity of ESCC, and investigate the potential underlying mechanisms. Methods SNHG8 expression in ESCC tissues and cell lines was determined via reverse-transcription quantitative polymerase chain reaction. The actions of SNHG8 on the malignant characteristics of ESCC were explored using CCK-8 assay, flow-cytometric analysis, Transwell migration and invasion assays, and tumor xenografts in nude mice. Results SNHG8 expression was significantly higher in ESCC tissues and cell lines. High SNHG8 expression was revealed to closely correlate with primary tumor invasion depth, lymph node metastases, TNM stage, and worse overall survival among patients with ESCC. Functional investigation showed that ablation of SNHG8 notably restricted ESCC cell proliferation, migration, and invasion while inducing apoptosis in vitro and hindered tumor growth in vivo. In the meantime, SNHG8 acted as a molecular sponge of microRNA-411 (miR-411) in ESCC. Furthermore, miR-411 exerted a tumor-suppressive effect on ESCC cells, and karyopherin alpha 2 (KPNA2) turned out to be a direct target gene of miR-411. Restoring KPNA2 expression neutralized the inhibitory effects of miR-411 overexpression on the malignant behaviors of ESCC cells. Moreover, silencing of miR-411 abrogated the influence of SNHG8 downregulation in ESCC cells. Conclusion SNHG8 may play oncogenic roles in the malignancy of ESCC by sponging miR-411 to increase KPNA2 expression. The SNHG8–miR-411–KPNA2 pathway may be a novel target for the treatment of patients with ESCC and offer potential biomarkers for the diagnosis and prognosis of ESCC.
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Affiliation(s)
- Huali Song
- Department of Gastroenterology, Sunshine Union Hospital, Weifang, Shandong 261061, People's Republic of China
| | - Jinxia Song
- Department of Oncology, Qingdao Eighth People's Hospital, Qingdao, Shandong 266100, People's Republic of China
| | - Lianwei Lu
- Department of Imaging, Binhai Hospital, Weifang People's Hospital, Weifang, Shandong 262737, People's Republic of China
| | - Shoubo Li
- Department of Thoracic Surgery, People's Hospital of Weifang Binhai Economic and Technological Development Zone, Weifang, Shandong 262737, People's Republic of China
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Yang Y, Li H, He Z, Xie D, Ni J, Lin X. MicroRNA‐488‐3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma. J Cell Biochem 2019; 120:18702-18713. [PMID: 31243806 DOI: 10.1002/jcb.29178] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 05/17/2019] [Accepted: 05/22/2019] [Indexed: 12/28/2022]
Affiliation(s)
- Yi Yang
- Department of Clinical Skills Center, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - He Li
- Department of Otolaryngoloy-Head and Neck Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhifeng He
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Deyao Xie
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jiangwei Ni
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaoming Lin
- Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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MicroRNA Dysregulation in Cutaneous Squamous Cell Carcinoma. Int J Mol Sci 2019; 20:ijms20092181. [PMID: 31052530 PMCID: PMC6540078 DOI: 10.3390/ijms20092181] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 04/15/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023] Open
Abstract
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and it can be locally invasive and metastatic to distant sites. MicroRNAs (miRNAs or miRs) are endogenous, small, non-coding RNAs of 19–25 nucleotides in length, that are involved in regulating gene expression at a post-transcriptional level. MicroRNAs have been implicated in diverse biological functions and diseases. In cancer, miRNAs can proceed either as oncogenic miRNAs (onco-miRs) or as tumor suppressor miRNAs (oncosuppressor-miRs), depending on the pathway in which they are involved. Dysregulation of miRNA expression has been shown in most of the tumors evaluated. MiRNA dysregulation is known to be involved in the development of cutaneous squamous cell carcinoma (CSCC). In this review, we focus on the recent evidence about the role of miRNAs in the development of CSCC and in the prognosis of this form of skin cancer.
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