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1
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Wang J, Zhang Z, Song L, Liu X, He X. Inhibition of esophageal squamous cell carcinoma progression by MIR210HG and activation of the P53 signaling pathway to promote apoptosis and autophagy. Eur J Med Res 2025; 30:269. [PMID: 40211342 PMCID: PMC11987309 DOI: 10.1186/s40001-025-02512-8] [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: 10/27/2024] [Accepted: 03/26/2025] [Indexed: 04/13/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) stands among the frequently occurring malignancies. The lack of efficient early detection methods and therapeutic approaches leads to a high mortality rate for ESCC. The long noncoding RNA MIR210HG is strongly related to various malignant tumors. However, its involvement in ESCC remains unexplored. Thus, this investigation aimed to assess the involvement of MIR210HG in ESCC development. METHODS The MIR210HG expression was analyzed in numerous tumor types through pan-cancer analysis of The Cancer Genome Atlas(TCGA) database. This research investigated the MIR210HG role in the survival and prognosis of individuals with ESCC. The biological functions of MIR210HG were examined by enrichment analyses, including GO, GSEA, and KEGG. Moreover, immune cell infiltration, tumor microenvironment (TME) characteristics, and immune checkpoint expression levels associated with MIR210HG were explored. To get more insight into the connection between MIR210HG and ESCC, we assessed related gene and protein expression using Western blotting and qRT-PCR. To evaluate the proliferation, invasion, migration, apoptosis, and autophagy of ESCC cells, various techniques were employed, including EdU proliferation tests, monodansylcadaverine (MDC) staining, wound healing assays, cell colony formation, transwell assays, flow cytometry, and an established xenograft mouse model. RESULTS MIR210HG exhibited low expression levels in ESCC. High expression of MIR210HG correlated with a higher survival rate among patients. The elevated expression of MIR210HG hindered the ESCC cell's ability to proliferate, invade, and migrate, both in vivo and in vitro settings. Furthermore, a positive correlation between MIR210HG and the P53 signaling pathway was observed, which could affect autophagy and apoptosis in ESCC cells. CONCLUSIONS MIR210HG emerges as a pivotal gene in ESCC, influencing both the immunity and prognosis of patients. Moreover, it may affect autophagy and apoptosis via the P53 signaling pathway. Overall, these outcomes present novel ideas for ESCC treatment.
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Affiliation(s)
- Jianyu Wang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
- Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China
| | - Zhenhu Zhang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
| | - Liang Song
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
| | - Xiangyan Liu
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
| | - Xiaopeng He
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China.
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2
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Lin PI, Lee YC, Chen IH, Chung HH. Pharmacological Modulation of Mutant TP53 with Oncotargets Against Esophageal Cancer and Therapy Resistance. Biomedicines 2025; 13:450. [PMID: 40002862 PMCID: PMC11852872 DOI: 10.3390/biomedicines13020450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 01/25/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025] Open
Abstract
The prevalence and deaths from esophageal cancer (EC) have recently increased. Although therapeutic strategies depend on the EC stage and recurrence, such as surgical intervention, chemotherapy, radiation therapy, chemoradiation therapy, targeted therapy, and immunotherapy, a more effective and novel treatment for EC is still required. This review briefly describes and summarizes some insightful oncotargets involved in the metabolic modulation of EC, including (1) cancer stem cells (CSCs) for EC progression, poor prognosis, tumor recurrence, and therapy resistance; (2) retinoic acid receptors (RARs) for esophageal carcinogenesis and regeneration; (3) phosphofructokinase (PFK) for EC-reprogrammed glycolysis; (4) lactate dehydrogenase (LDH) as an EC peripheral blood biomarker; and (5) hypoxia-inducible factor-1 alpha (HIF-1α) for the tumor microenvironment under hypoxic conditions. Moreover, the aforementioned oncotargets can be modulated by mutant TP53 and have their own features in the carcinogenesis, differentiation, proliferation, and metastasis of EC. Thus, the clarification of pharmacological mechanisms regarding the interaction between mutant TP53 and the abovementioned oncotargets could provide precise and perspective opinions for minimizing prediction errors, reducing therapy resistance, and developing novel drugs against EC.
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Affiliation(s)
- Pei-I Lin
- Department of Nursing, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 833401, Taiwan;
| | - Yu-Cheng Lee
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei City 110301, Taiwan;
| | - I-Hung Chen
- Division of Urology, Department of Surgery, National Cheng Kung University Hospital Douliu Branch, Yunlin County 640003, Taiwan;
| | - Hsien-Hui Chung
- Department of Pharmacy & Clinical Trial Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung City 813414, Taiwan
- St. Edmund Hall, University of Oxford, Oxford OX1 4AR, UK
- Preventive Medicine Program, Center for General Education, Chung Yuan Christian University, Taoyuan City 320314, Taiwan
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung County 907101, Taiwan
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3
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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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4
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Wang Y, Sun Z, Zhao Z, Pang J, Chen J. Recent Progress in the Development of Glucose Transporter (GLUT) Inhibitors. J Med Chem 2025; 68:1033-1050. [PMID: 39746141 DOI: 10.1021/acs.jmedchem.4c02717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Cancer cells exhibit an accelerated glucose uptake and glycolysis. The transmembrane uptake of glucose requires specific carrier proteins, such as glucose transporters (GLUTs) and sodium-coupled glucose cotransporters (SGLTs). GLUTs transport glucose independently of the energy supply and have become promising targets for cancer therapy. This Perspective mainly focuses on the current research progress and design strategy of GLUT inhibitors, particularly those targeting class I (GLUT1-4). To the best of our knowledge, this is the first systematic interpretation of the research progress, opportunities, and challenges faced in the development of GLUT inhibitors from a medicinal chemistry perspective. We hope that this Perspective will provide insights into the development of GLUT inhibitors, offering a feasible approach to cancer therapy.
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Affiliation(s)
- Yuxuan Wang
- Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510280, China
| | - Zhiqiang Sun
- Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Zean Zhao
- Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jianxin Pang
- Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jianjun Chen
- Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
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5
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He M, Qi Y, Zheng ZM, Sha M, Zhao X, Chen YR, Chen ZH, Qian RY, Yao J, Yang ZD. Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma. World J Gastrointest Oncol 2024; 16:4194-4208. [DOI: 10.4251/wjgo.v16.i10.4194] [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: 01/08/2024] [Revised: 06/09/2024] [Accepted: 06/28/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND The clinical effects and detailed roles of long non-coding RNA (LncRNA) steroid receptor RNA activator 1 (SRA1) in esophageal squamous cell carcinoma (ESCC) remain ambiguous. In the present study, the complementary sites between lncRNA SRA1, miRNA-363-5p, and phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.
AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.
METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired. SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction. Cell counting Kit-8 assay, transwell invasion assay, glycolysis assay, and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1. The t-test and the χ2 test were used for comparison between groups. Survival curve analysis was performed using the Kaplan-Meier method.
RESULTS SRA1 downregulation was identified in ESCC. ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression. The introduction of SRA1 inhibited cell proliferation, glucose uptake, and lactate production in ESCC. In vivo, the growth of ESCC was hindered by SRA1 overexpression. Then, SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p. Lastly, the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.
CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis. The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.
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Affiliation(s)
- Ming He
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Ye Qi
- Department of Nursing, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Ze-Mao Zheng
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Min Sha
- Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou 225300, Zhejiang Province, China
| | - Xiang Zhao
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Yu-Rao Chen
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Zheng-Hai Chen
- Department of Thoracic Surgery, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Rong-Yu Qian
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Juan Yao
- Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
| | - Zheng-Dong Yang
- Department of Thoracic Surgery, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
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6
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Li Q, Lin G, Zhang K, Liu X, Li Z, Bing X, Nie Z, Jin S, Guo J, Min X. Hypoxia exposure induces lactylation of Axin1 protein to promote glycolysis of esophageal carcinoma cells. Biochem Pharmacol 2024; 226:116415. [PMID: 38972426 DOI: 10.1016/j.bcp.2024.116415] [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: 04/02/2024] [Revised: 07/01/2024] [Accepted: 07/04/2024] [Indexed: 07/09/2024]
Abstract
The hypoxic microenvironment in esophageal carcinoma is an important factor promoting the rapid progression of malignant tumor. This study was to investigate the lactylation of Axin1 on glycolysis in esophageal carcinoma cells under hypoxia exposure. Hypoxia treatment increases pan lysine lactylation (pan-kla) levels of both TE1 and EC109 cells. Meanwhile, ECAR, glucose consumption and lactate production were also upregulated in both TE1 and EC109 cells. The expression of embryonic stem cell transcription factors NANOG and SOX2 were enhanced in the hypoxia-treated cells. Axin1 overexpression partly reverses the induction effects of hypoxia treatment in TE1 and EC109 cells. Moreover, lactylation of Axin1 protein at K147 induced by hypoxia treatment promotes ubiquitination modification of Axin1 protein to promote glycolysis and cell stemness of TE1 and EC109 cells. Mutant Axin1 can inhibit ECAR, glucose uptake, lactate secretion, and cell stemness in TE1 and EC109 cells under normal or hypoxia conditions. Meanwhile, mutant Axin1 further enhanced the effects of 2-DG on inhibiting glycolysis and cell stemness. Overexpression of Axin1 also inhibited tumor growth in vivo, and was related to suppressing glycolysis. In conclusion, hypoxia treatment promoted the glycolysis and cell stemness of esophageal carcinoma cells, and increased the lactylation of Axin1 protein. Overexpression of Axin1 functioned as a glycolysis inhibitor, and suppressed the effects of hypoxia exposure in vitro and inhibited tumor growth in vivo. Mechanically, hypoxia induces the lactylation of Axin1 protein and promotes the ubiquitination of Axin1 to degrade the protein, thereby exercising its anti-glycolytic function.
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Affiliation(s)
- Qian Li
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China; Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Guihu Lin
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China
| | - Kaihua Zhang
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China
| | - Xinbo Liu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhantao Li
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China
| | - Xiaohan Bing
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China
| | - Zhenkai Nie
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China
| | - Shan Jin
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China
| | - Jin Guo
- School of Medical Technology, Beijing Institute of Technology, Beijing, China.
| | - Xianjun Min
- Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China.
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Zang Y, Wang A, Zhang J, Xia M, Jiang Z, Jia B, Lu C, Chen C, Wang S, Zhang Y, Wang C, Cao X, Niu Z, He C, Bai X, Tian S, Zhai G, Cao H, Chen Y, Zhang K. Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma. iScience 2024; 27:110188. [PMID: 38989468 PMCID: PMC11233973 DOI: 10.1016/j.isci.2024.110188] [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: 02/22/2024] [Revised: 05/07/2024] [Accepted: 06/03/2024] [Indexed: 07/12/2024] Open
Abstract
Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.
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Affiliation(s)
- Yong Zang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Aiyuan Wang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Jianji Zhang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Mingxin Xia
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Zixin Jiang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Bona Jia
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Congcong Lu
- Frontier Center for Cell Response, College of Life Sciences, Nankai University, Tianjin 300071, China
| | - Chen Chen
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Siyu Wang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Yingao Zhang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Chen Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Xinyi Cao
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Ziping Niu
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Chaoran He
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Xue Bai
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Shanshan Tian
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Guijin Zhai
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Yupeng Chen
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
- Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China
| | - Kai Zhang
- The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin Medical University, Tianjin 300070, China
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8
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Wang Z, Sun X, Li Z, Yu H, Li W, Xu Y. Metabolic reprogramming in esophageal squamous cell carcinoma. Front Pharmacol 2024; 15:1423629. [PMID: 38989149 PMCID: PMC11233760 DOI: 10.3389/fphar.2024.1423629] [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: 04/26/2024] [Accepted: 06/06/2024] [Indexed: 07/12/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignancy with high incidence in China. Due to the lack of effective molecular targets, the prognosis of ESCC patients is poor. It is urgent to explore the pathogenesis of ESCC to identify promising therapeutic targets. Metabolic reprogramming is an emerging hallmark of ESCC, providing a novel perspective for revealing the biological features of ESCC. In the hypoxic and nutrient-limited tumor microenvironment, ESCC cells have to reprogram their metabolic phenotypes to fulfill the demands of bioenergetics, biosynthesis and redox homostasis of ESCC cells. In this review, we summarized the metabolic reprogramming of ESCC cells that involves glucose metabolism, lipid metabolism, and amino acid metabolism and explore how reprogrammed metabolism provokes novel opportunities for biomarkers and potential therapeutic targets of ESCC.
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Affiliation(s)
- Ziyi Wang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiangyu Sun
- Department of Breast Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zehui Li
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Huidong Yu
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wenya Li
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yan Xu
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, Liaoning, China
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9
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Zhang L, Wang Y, Gao J, Zhou X, Huang M, Wang X, He Z. Non‑coding RNA: A promising diagnostic biomarker and therapeutic target for esophageal squamous cell carcinoma (Review). Oncol Lett 2024; 27:255. [PMID: 38646493 PMCID: PMC11027111 DOI: 10.3892/ol.2024.14388] [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: 11/04/2023] [Accepted: 03/22/2024] [Indexed: 04/23/2024] Open
Abstract
Esophageal cancer (EC) is a common form of malignant tumor in the digestive system that is classified into two types: Esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinoma. ESCC is known for its early onset of symptoms, which can be difficult to identify, as well as its rapid progression and tendency to develop drug resistance to chemotherapy and radiotherapy. These factors contribute to the high incidence of disease and low cure rate. Therefore, a diagnostic biomarker and therapeutic target need to be identified for ESCC. Non-coding RNAs (ncRNAs) are a class of molecules that are transcribed from DNA but do not encode proteins. Initially, ncRNAs were considered to be non-functional segments generated during transcription. However, with advancements in high-throughput sequencing technologies in recent years, ncRNAs have been associated with poor prognosis, drug resistance and progression of ESCC. The present study provides a comprehensive overview of the biogenesis, characteristics and functions of ncRNAs, particularly focusing on microRNA, long ncRNAs and circular RNAs. Furthermore, the ncRNAs that could potentially be used as diagnostic biomarkers and therapeutic targets for ESCC are summarized to highlight their application value and prospects in ESCC.
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Affiliation(s)
- Longze Zhang
- Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Yanyang Wang
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
- Department of Cell Engineering Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Jianmei Gao
- School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Xue Zhou
- Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Minglei Huang
- Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Xianyao Wang
- Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Zhixu He
- Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
- Department of Cell Engineering Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
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10
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Tan Z, Luan S, Wang X, Jiao W, Jiang P. Mechanism study of lncRNA RMRP regulating esophageal squamous cell carcinoma through miR-580-3p/ATP13A3 axis. Discov Oncol 2024; 15:150. [PMID: 38722543 PMCID: PMC11082096 DOI: 10.1007/s12672-024-00990-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 04/19/2024] [Indexed: 05/12/2024] Open
Abstract
OBJECTIVE It is well-known that lncRNAs regulate energy metabolism in tumors. This study focused on the action of RMRP on esophageal squamous cell carcinoma (ESCC) cell proliferation, apoptosis, and glycolysis. METHODS In the resected ESCC tissues and adjacent tissues from patients, RMRP/miR-580-3p/ATP13A3 expressions were evaluated. ESCC cell proliferation rates and apoptotic rates were measured by CCK-8 and flow cytometry, respectively. Apoptosis related markers were examined by Western blot. Moreover, glucose uptake, lactic acid, and ATP were measured by commercial kits, whereas HK2 and PKM2 were evaluated by Western blot to study ESCC cell glycolysis. Finally, the editing program of RMRP/miR-580-3p/ATP13A3 was translated by luciferase reporter assay and RIP analysis. RESULTS RMRP and ATP13A3 were induced, while miR-580-3p was reduced in their expression in ESCC tissues. Silencing RMRP reduced proliferation, glycolysis, and anti-apoptosis ability of ESCC cells. RMRP sequestered miR-580-3p to target ATP13A3. Silenced ATP13A3 or overexpressed miR-580-3p rescued overexpressed RMRP-mediated promotion of proliferation, glycolysis, and anti-apoptosis of ESCC cells. CONCLUSION RMRP accelerates ESCC progression through the miR-580-3p/ATP13A3 axis, renewing a reference for lncRNA-based therapies for tumors.
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Affiliation(s)
- ZiRui Tan
- The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Chang'an District, Shijiazhuang City, 050000, Hebei Province, China
| | - ShengJie Luan
- Department of Tumor Chemoradiotherapy, Central Hospital of Qinghe County, Xingtai City, 054800, Hebei Province, China
| | - XiaoPeng Wang
- Department of Tumor Chemoradiotherapy, Central Hospital of Qinghe County, Xingtai City, 054800, Hebei Province, China
| | - WenPeng Jiao
- The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Chang'an District, Shijiazhuang City, 050000, Hebei Province, China
| | - Pu Jiang
- The Fourth Hospital of Hebei Medical University, No. 12, Jiankang Road, Chang'an District, Shijiazhuang City, 050000, Hebei Province, China.
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11
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Wang K, Lu Y, Li H, Zhang J, Ju Y, Ouyang M. Role of long non-coding RNAs in metabolic reprogramming of gastrointestinal cancer cells. Cancer Cell Int 2024; 24:15. [PMID: 38184562 PMCID: PMC10770979 DOI: 10.1186/s12935-023-03194-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/26/2023] [Indexed: 01/08/2024] Open
Abstract
Metabolic reprogramming, which is recognized as a hallmark of cancer, refers to the phenomenon by which cancer cells change their metabolism to support their increased biosynthetic demands. Tumor cells undergo substantial alterations in metabolic pathways, such as glycolysis, oxidative phosphorylation, pentose phosphate pathway, tricarboxylic acid cycle, fatty acid metabolism, and amino acid metabolism. Latest studies have revealed that long non-coding RNAs (lncRNAs), a group of non-coding RNAs over 200 nucleotides long, mediate metabolic reprogramming in tumor cells by regulating the transcription, translation and post-translational modification of metabolic-related signaling pathways and metabolism-related enzymes through transcriptional, translational, and post-translational modifications of genes. In addition, lncRNAs are closely related to the tumor microenvironment, and they directly or indirectly affect the proliferation and migration of tumor cells, drug resistance and other processes. Here, we review the mechanisms of lncRNA-mediated regulation of glucose, lipid, amino acid metabolism and tumor immunity in gastrointestinal tumors, aiming to provide more information on effective therapeutic targets and drug molecules for gastrointestinal tumors.
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Affiliation(s)
- Kang Wang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, 528300, Guangdong, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510080, Guangdong, China
| | - Yan Lu
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, 528300, Guangdong, China
| | - Haibin Li
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, 528300, Guangdong, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510080, Guangdong, China
| | - Jun Zhang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, 528300, Guangdong, China
- Guangdong Medical University, Dongguan, 523808, China
| | - Yongle Ju
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, 528300, Guangdong, China.
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510080, Guangdong, China.
| | - Manzhao Ouyang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan), Shunde, Foshan, 528300, Guangdong, China.
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510080, Guangdong, China.
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