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Temaj G, Saha S, Chichiarelli S, Telkoparan-Akillilar P, Nuhii N, Hadziselimovic R, Saso L. Polyploid giant cancer cells: Underlying mechanisms, signaling pathways, and therapeutic strategies. Crit Rev Oncol Hematol 2025; 213:104802. [PMID: 40484156 DOI: 10.1016/j.critrevonc.2025.104802] [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: 04/12/2025] [Revised: 05/26/2025] [Accepted: 06/04/2025] [Indexed: 06/19/2025] Open
Abstract
Polyploid giant cancer cells (PGCCs) are characterized by enlarged nuclei, association with tumors, and resistance to treatment, contributing significantly to cellular heterogeneity. These cells arise from endoreplication and cell fusion, often triggered by stressors such as radiation and chemotherapy. PGCCs exhibit chromosomal instability and aneuploidy, leading to poor prognosis in various cancers. Key features include the ability to produce progeny cells via amitotic division and the expression of cancer stem cell markers. PGCC formation and function involve signaling pathways like cell fusion (GCM1/syncytin-1), cell cycle control, stress response, and EMT. Understanding these pathways is crucial for identifying therapeutic targets. Current therapeutic strategies targeting PGCCs involve drugs like azacitidine, decitabine, and zoledronic acid, as well as DNMT inhibitors in combination therapies. These approaches aim to reverse drug resistance and enhance antitumor efficacy. Furthermore, microRNAs (miRNAs) are pivotal in regulating gene expression and influencing the cell cycle, proliferation, and apoptosis. Cataloging miRNAs and understanding their function is critical for developing potential cancer treatments. Researchers are exploring miRNA-based modulation of signaling pathways to block tumor growth. This review highlights the complex biology of PGCCs and emphasizes the need for targeted therapies to improve cancer treatment outcomes.
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Affiliation(s)
- Gazmend Temaj
- Faculty of Pharmacy, College UBT, Prishtina 10000, Kosovo
| | - Sarmistha Saha
- Department of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura, Uttar Pradesh 00185, India.
| | - Silvia Chichiarelli
- Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of Rome, Rome 00185, Italy
| | | | - Nexhibe Nuhii
- Department of Pharmacy, Faculty of Medical Sciences, State University of Tetovo, Tetovo 1200, North Macedonia
| | - Rifat Hadziselimovic
- Faculty of Science, University of Sarajevo, Sarajevo 71000, Bosnia and Herzegovina
| | - Luciano Saso
- Department of Physiology and Pharmacology "Vittorio Erspamer", La Sapienza University, Rome 00185, Italy
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2
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Shen C, Chen Z, Jiang J, Zhang Y, Chen X, Xu W, Peng R, Zuo W, Jiang Q, Fan Y, Fang X, Zheng B. Identification and validation of fatty acid metabolism-related lncRNA signatures as a novel prognostic model for clear cell renal cell carcinoma. Sci Rep 2023; 13:7043. [PMID: 37120692 PMCID: PMC10148808 DOI: 10.1038/s41598-023-34027-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 04/22/2023] [Indexed: 05/01/2023] Open
Abstract
Clear cell renal cell carcinoma (ccRCC) is a main subtype of renal cancer, and advanced ccRCC frequently has poor prognosis. Many studies have found that lipid metabolism influences tumor development and treatment. This study was to examine the prognostic and functional significance of genes associated with lipid metabolism in individuals with ccRCC. Using the database TCGA, differentially expressed genes (DEGs) associated with fatty acid metabolism (FAM) were identified. Prognostic risk score models for genes related to FAM were created using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Our findings demonstrate that the prognosis of patients with ccRCC correlate highly with the profiles of FAM-related lncRNAs (AC009166.1, LINC00605, LINC01615, HOXA-AS2, AC103706.1, AC009686.2, AL590094.1, AC093278.2). The prognostic signature can serve as an independent predictive predictor for patients with ccRCC. The predictive signature's diagnostic effectiveness was superior to individual clinicopathological factors. Between the low- and high-risk groups, immunity research revealed a startling difference in terms of cells, function, and checkpoint scores. Chemotherapeutic medications such lapatinib, AZD8055, and WIKI4 had better outcomes for patients in the high-risk group. Overall, the predictive signature can help with clinical selection of immunotherapeutic regimens and chemotherapeutic drugs, improving prognosis prediction for ccRCC patients.
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Affiliation(s)
- Cheng Shen
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China
- Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Zhan Chen
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China
- Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Jie Jiang
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China
- Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Yong Zhang
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China
- Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Xinfeng Chen
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Wei Xu
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China
- Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Rui Peng
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China
- Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Wenjing Zuo
- Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong, China
| | - Qian Jiang
- Department of Paediatric, Chinese Medicine Hospital of Rudong, Nantong, China
| | - Yihui Fan
- Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong, China
| | - Xingxing Fang
- Department of Nephrology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China.
| | - Bing Zheng
- Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, China.
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Ghafouri-Fard S, Askari A, Behzad Moghadam K, Hussen BM, Taheri M, Samadian M. A review on the role of ZEB1-AS1 in human disorders. Pathol Res Pract 2023; 245:154486. [PMID: 37120907 DOI: 10.1016/j.prp.2023.154486] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 04/19/2023] [Accepted: 04/24/2023] [Indexed: 05/02/2023]
Abstract
ZEB1 Antisense RNA 1 (ZEB1-AS1) is a type of RNA characterized as long non-coding RNA (lncRNA). This lncRNA has important regulatory roles on its related gene, Zinc Finger E-Box Binding Homeobox 1 (ZEB1). In addition, role of ZEB1-AS1 has been approved in diverse malignancies such as colorectal cancer, breast cancer, glioma, hepatocellular carcinoma and gastric cancer. ZEB1-AS1 serves as a sponge for a number of microRNAs, namely miR-577, miR-335-5p, miR-101, miR-505-3p, miR-455-3p, miR-205, miR-23a, miR-365a-3p, miR-302b, miR-299-3p, miR-133a-3p, miR-200a, miR-200c, miR-342-3p, miR-214, miR-149-3p and miR-1224-5p. In addition to malignant conditions, ZEB1-AS1 has functional role in non-malignant conditions like diabetic nephropathy, diabetic lung, arthrosclerosis, Chlamydia trachomatis infection, pulmonary fibrosis and ischemic stroke. This review outlines different molecular mechanisms of ZEB1-AS1 in a variety of disorders and highlights its importance in their pathogenesis.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arian Askari
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Mohammad Taheri
- Institue of Human Genetics, Jena University Hospital, Jena, Germany; Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Samadian
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Dey Ghosh R, Guha Majumder S. Circulating Long Non-Coding RNAs Could Be the Potential Prognostic Biomarker for Liquid Biopsy for the Clinical Management of Oral Squamous Cell Carcinoma. Cancers (Basel) 2022; 14:5590. [PMID: 36428681 PMCID: PMC9688117 DOI: 10.3390/cancers14225590] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/29/2022] [Accepted: 08/30/2022] [Indexed: 11/16/2022] Open
Abstract
Long non-coding RNA (lncRNA) have little or no coding potential. These transcripts are longer than 200 nucleotides. Since lncRNAs are master regulators of almost all biological processes, recent evidence proves that aberrantly expressed lncRNAs are pathogenic for oral squamous cell carcinoma (OSCC) and other diseases. LncRNAs influence chromatin modifications, transcriptional modifications, post-transcriptional modifications, genomic imprinting, cell proliferation, invasion, metastasis, and apoptosis. Consequently, they have an impact on the disease transformation, progression, and morbidity in OSCC. Therefore, circulating lncRNAs could be the potential cancer biomarker for the better clinical management (diagnosis, prognosis, and monitoring) of OSCC to provide advanced treatment strategies and clinical decisions. In this review, we report and discuss the recent understandings and perceptions of dysregulated lncRNAs with a focus on their clinical significance in OSCC-disease monitoring and treatment. Evidence clearly indicates that a specific lncRNA expression signature could act as an indicator for the early prediction of diagnosis and prognosis for the initiation, progression, recurrence, metastasis and other clinical prognostic-factors (overall survival, disease-free survival, etc.) in OSCC. The present review demonstrates the current knowledge that all potential lncRNA expression signatures are molecular biomarkers for the early prediction of prognosis in OSCC. Finally, the review provides information about the clinical significance, challenges and limitations of the clinical usage of circulating lncRNAs in a liquid biopsy method in early, pre-symptomatic, sub-clinical, accurate OSCC prognostication. More studies on lncRNA are required to unveil the biology of the inherent mechanisms involved in the process of the development of differential prognostic outcomes in OSCC.
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Affiliation(s)
- Ruma Dey Ghosh
- Molecular Biology Department, Netaji Subhas Chandra Bose Cancer Research Institute, 3081 Nayabad, Kolkata 700094, India
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Identification of fatty acid metabolism-related lncRNAs in the prognosis and immune microenvironment of colon adenocarcinoma. Biol Direct 2022; 17:19. [PMID: 35902970 PMCID: PMC9331591 DOI: 10.1186/s13062-022-00332-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/23/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Cancer metabolism is largely altered compared to normal cells. This study aims to explore critical metabolism pathways in colon adenocarcinoma (COAD), and reveal the possible mechanism of their role in cancer progression. METHODS Expression data and sequencing data of COAD samples were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The expression profiles between tumor and normal samples were compared to identify differential metabolism pathways through single sample gene set enrichment analysis. RESULTS Fatty acid synthesis was identified as a key metabolism pathway in COAD. Based on fatty acid-related lncRNAs, two molecular subtypes (C1 and C2) were defined. C2 subtype with worse prognosis had higher immune infiltration and higher expression of immune checkpoints. Five transcription factors (TFs) including FOS, JUN, HIF1A, STAT3 and STAT2 were highly expressed in C2 subtype. Five fatty acid-related lncRNAs were identified to be biomarkers for predicting COAD prognosis. Finally, further experients showed that knockdown of lncRNA PAXIP1-AS1 decreased the triglyceride content and the fatty acid synthase and acetyl-CoA carboxylase 1 expressions, which suggested that lncRNA PAXIP1-AS1 plays an important role in fatty acid metabolism of COAD. CONCLUSIONS This study demonstrated that fatty acid synthesis was greatly altered in COAD. Fatty acid-related lncRNAs were speculated to be involved in cancer progression through associating with TFs. The five screened TFs may serve as new drug targets for treating COAD.
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6
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Ghafouri-Fard S, Khoshbakht T, Hussen BM, Baniahmad A, Branicki W, Taheri M, Eghbali A. Emerging Role of Non-Coding RNAs in Senescence. Front Cell Dev Biol 2022; 10:869011. [PMID: 35865636 PMCID: PMC9294638 DOI: 10.3389/fcell.2022.869011] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
Senescence is defined as a gradual weakening of functional features of a living organism. Cellular senescence is a process that is principally aimed to remove undesirable cells by prompting tissue remodeling. This process is also regarded as a defense mechanism induced by cellular damage. In the course of oncogenesis, senescence can limit tumor progression. However, senescence participates in the pathoetiology of several disorders such as fibrotic disorders, vascular disorders, diabetes, renal disorders and sarcopenia. Recent studies have revealed contribution of different classes of non-coding RNAs in the cellular senescence. Long non-coding RNAs, microRNAs and circular RNAs are three classes of these transcripts whose contributions in this process have been more investigated. In the current review, we summarize the available literature on the impact of these transcripts in the cellular senescence.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tayyebeh Khoshbakht
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq
- Center of Research and Strategic Studies, Lebanese French University, Erbil, Iraq
| | - Aria Baniahmad
- Institute of Human Genetics, Jena University Hospitals, Jena, Germany
- *Correspondence: Aria Baniahmad, ; Mohammad Taheri, ; Ahmad Eghbali,
| | - Wojciech Branicki
- Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospitals, Jena, Germany
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- *Correspondence: Aria Baniahmad, ; Mohammad Taheri, ; Ahmad Eghbali,
| | - Ahmad Eghbali
- Anesthesiology Research Center, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- *Correspondence: Aria Baniahmad, ; Mohammad Taheri, ; Ahmad Eghbali,
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7
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Dong P, Wang F, Taheri M, Xiong Y, Ihira K, Kobayashi N, Konno Y, Yue J, Watari H. Long Non-Coding RNA TMPO-AS1 Promotes GLUT1-Mediated Glycolysis and Paclitaxel Resistance in Endometrial Cancer Cells by Interacting With miR-140 and miR-143. Front Oncol 2022; 12:912935. [PMID: 35712514 PMCID: PMC9195630 DOI: 10.3389/fonc.2022.912935] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 04/29/2022] [Indexed: 01/05/2023] Open
Abstract
Increased glycolysis in tumor cells is frequently associated with drug resistance. Overexpression of glucose transporter-1 (GLUT1) promotes the Warburg effect and mediates chemoresistance in various cancers. Aberrant GLUT1 expression is considered as an essential early step in the development of endometrial cancer (EC). However, its role in EC glycolysis and chemoresistance and the upstream mechanisms underlying GLUT1 overexpression, remain undefined. Here, we demonstrated that GLUT1 was highly expressed in EC tissues and cell lines and that high GLUT1 expression was associated with poor prognosis in EC patients. Both gain-of-function and loss-of-function studies showed that GLUT1 increased EC cell proliferation, invasion, and glycolysis, while also making them resistant to paclitaxel. The long non-coding RNA TMPO-AS1 was found to be overexpressed in EC tissues and to be negatively associated with EC patient outcomes. RNA-immunoprecipitation and luciferase reporter assays confirmed that TMPO-AS1 elevated GLUT1 expression by directly binding to two critical tumor suppressor microRNAs (miR-140 and miR-143). Downregulation of TMPO-AS1 remarkably reduced EC cell proliferation, invasion, glycolysis, and paclitaxel resistance in EC cells. This study established that dysregulation of the TMPO-AS1-miR-140/miR-143 axis contributes to glycolysis and drug resistance in EC cells by up-regulating GLUT1 expression. Thus, inhibiting TMPO-AS1 and GLUT1 may prove beneficial in overcoming glycolysis-induced paclitaxel resistance in patients with EC.
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Affiliation(s)
- Peixin Dong
- Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan
| | - Feng Wang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Jiangsu, China
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Institute of Human Genetics, Jena University Hospital, Jena, Germany
| | - Ying Xiong
- Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Kei Ihira
- Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan
| | - Noriko Kobayashi
- Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan
| | - Yosuke Konno
- Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan
| | - Junming Yue
- Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, United States.,Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Hidemichi Watari
- Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan
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He N, Xiang L, Chen L, Tong H, Wang K, Zhao J, Song F, Yang H, Wei X, Jiao Z. The role of long non-coding RNA FGD5-AS1 in cancer. Bioengineered 2022; 13:11026-11041. [PMID: 35475392 PMCID: PMC9208527 DOI: 10.1080/21655979.2022.2067292] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) refers to a class of RNAs that have at least 200 nucleotides and do not encode proteins, and the relationship between lncRNA and cancer has recently attracted considerable research attention. The lncRNA FGD5-AS1 is a newly discovered lncRNA with a length of 3772 nucleotides. Studies have found that FGD5-AS1 is abnormally highly expressed in many cancer tissues and was closely related to the lymph node metastasis, tumor invasion, survival time, and recurrence rate of various cancers. Mechanistic analyses show that FGD5-AS1 can stabilize mRNA expression by sponging miRNA, which not only induces cancer cell proliferation, metastasis, invasion, and chemoresistance in vitro, but also promotes tumor growth and metastasis in vivo. In addition, FGD5-AS1 can serve as a diagnostic or prognostic marker for a variety of cancers. This review demonstrates the clinical significance of FGD5-AS1 in human cancer and its role in tumorigenesis and tumor progression.
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Affiliation(s)
- Na He
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Linbiao Xiang
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Lei Chen
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Haobin Tong
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Keshen Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Jie Zhao
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Feixue Song
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Hanteng Yang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Xinyuan Wei
- Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Zuoyi Jiao
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
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Zhang Z, Wang F, Zhang J, Zhan W, Zhang G, Li C, Zhang T, Yuan Q, Chen J, Guo M, Xu H, Yu F, Wang H, Wang X, Kong W. An m6A-Related lncRNA Signature Predicts the Prognosis of Hepatocellular Carcinoma. Front Pharmacol 2022; 13:854851. [PMID: 35431958 PMCID: PMC9006777 DOI: 10.3389/fphar.2022.854851] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 03/07/2022] [Indexed: 12/24/2022] Open
Abstract
Objective: The purpose of this study was to establish an N6-methylandenosine (m6A)-related long non-coding RNA (lncRNA) signature to predict the prognosis of hepatocellular carcinoma (HCC). Methods: Pearson correlation analysis was used to identify m6A-related lncRNAs. We then performed univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct an m6A-related lncRNA signature. Based on the cutoff value of the risk score determined by the X-title software, we divided the HCC patients into high -and low-risk groups. A time-dependent ROC curve was used to evaluate the predictive value of the model. Finally, we constructed a nomogram based on the m6A-related lncRNA signature. Results: ZEB1-AS1, MIR210HG, BACE1-AS, and SNHG3 were identified to comprise an m6A-related lncRNA signature. These four lncRNAs were upregulated in HCC tissues compared to normal tissues. The prognosis of patients with HCC in the low-risk group was significantly longer than that in the high-risk group. The M6A-related lncRNA signature was significantly associated with clinicopathological features and was established as a risk factor for the prognosis of patients with HCC. The nomogram based on the m6A-related lncRNA signature had a good distinguishing ability and consistency. Conclusion: We identified an m6A-related lncRNA signature and constructed a nomogram model to evaluate the prognosis of patients with HCC.
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Affiliation(s)
- Zhenyu Zhang
- Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei, China
| | - Fangkai Wang
- Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jianlin Zhang
- Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wenjing Zhan
- Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei, China
| | - Gaosong Zhang
- Department Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chong Li
- Department Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Tongyuan Zhang
- Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qianqian Yuan
- Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei, China
| | - Jia Chen
- Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Manyu Guo
- Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei, China
| | - Honghai Xu
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Feng Yu
- Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hengyi Wang
- Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xingyu Wang
- Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Weihao Kong
- Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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10
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Ge J, Wang B, Zhao S, Xu J. Inhibition of lncRNA NEAT1 sensitizes medulloblastoma cells to cisplatin through modulating the miR-23a-3p-glutaminase (GLS) axis. Bioengineered 2022; 13:7670-7682. [PMID: 35313796 PMCID: PMC9208477 DOI: 10.1080/21655979.2021.2008695] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Medulloblastoma (MB) is a commonly occurring brain malignancy in adolescence. Currently, the combination of chemotherapy with subsequent irradiation is a regular therapeutic strategy. However, high dosage of chemotherapy is associated with drug resistance and side effects. The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), which is frequently overexpressed in diverse human tumors, is correlated with worse survival rate in cancer patients. Currently, the precise roles of NEAT1 in MB and chemoresistance remain unclear. Our study aimed to investigate the biological functions of NEAT1 in cisplatin-resistant medulloblastoma. We report that NEAT1 was significantly upregulated in medulloblastoma patient specimens. Silencing NEAT1 significantly suppressed MB cell proliferation and sensitized MB cells to cisplatin. In cisplatin-resistant MB cell line, DAOY Cis R, NEAT1 expression, and glutamine metabolism were remarkably upregulated in cisplatin-resistant cells. Under low glutamine supply, cisplatin-resistant cells displayed increased cisplatin sensitivity. Bioinformatical analysis and luciferase assay uncovered that NEAT1 functions as a ceRNA of miR-23a-3p to downregulate its expressions in MB cells. Moreover, miR-23a-3p was apparently downregulated in MB patient tissues and cisplatin resistant MB cells. We identified GLS (glutaminase), a glutamine metabolism enzyme, was directly targeted by miR-23a-3p in MB cells. Rescue experiments demonstrated restoration of miR-23a-3p in NEAT1-overexpressing DAOY cisplatin resistant cells successfully overcame the NEAT1-promoted cisplatin resistance by targeting GLS. In general, our results revealed new molecular mechanisms for the lncRNA-NEAT1-mediated cisplatin sensitivity of MB.
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Affiliation(s)
- Jingjing Ge
- Department of Pediatrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Baohong Wang
- Department of Pediatrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Shuai Zhao
- Department of Pediatrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Jiaju Xu
- Department of Pediatrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
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11
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Adhikari S, Guha D, Mohan C, Mukherjee S, Tyler JK, Das C. Reprogramming Carbohydrate Metabolism in Cancer and Its Role in Regulating the Tumor Microenvironment. Subcell Biochem 2022; 100:3-65. [PMID: 36301490 PMCID: PMC10760510 DOI: 10.1007/978-3-031-07634-3_1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Altered metabolism has become an emerging feature of cancer cells impacting their proliferation and metastatic potential in myriad ways. Proliferating heterogeneous tumor cells are surrounded by other resident or infiltrating cells, along with extracellular matrix proteins, and other secretory factors constituting the tumor microenvironment. The diverse cell types of the tumor microenvironment exhibit different molecular signatures that are regulated at their genetic and epigenetic levels. The cancer cells elicit intricate crosstalks with these supporting cells, exchanging essential metabolites which support their anabolic processes and can promote their survival, proliferation, EMT, angiogenesis, metastasis and even therapeutic resistance. In this context, carbohydrate metabolism ensures constant energy supply being a central axis from which other metabolic and biosynthetic pathways including amino acid and lipid metabolism and pentose phosphate pathway are diverged. In contrast to normal cells, increased glycolytic flux is a distinguishing feature of the highly proliferative cancer cells, which supports them to adapt to a hypoxic environment and also protects them from oxidative stress. Such rewired metabolic properties are often a result of epigenetic alterations in the cancer cells, which are mediated by several factors including, DNA, histone and non-histone protein modifications and non-coding RNAs. Conversely, epigenetic landscapes of the cancer cells are also dictated by their diverse metabolomes. Altogether, this metabolic and epigenetic interplay has immense potential for the development of efficient anti-cancer therapeutic strategies. In this book chapter we emphasize upon the significance of reprogrammed carbohydrate metabolism in regulating the tumor microenvironment and cancer progression, with an aim to explore the different metabolic and epigenetic targets for better cancer treatment.
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Affiliation(s)
- Swagata Adhikari
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India
- Homi Bhaba National Institute, Mumbai, India
| | - Deblina Guha
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India
| | - Chitra Mohan
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Shravanti Mukherjee
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India
| | - Jessica K Tyler
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Chandrima Das
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India.
- Homi Bhaba National Institute, Mumbai, India.
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12
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Fang Y, Yang Y, Li N, Zhang XL, Huang HF. Emerging role of long noncoding RNAs in recurrent hepatocellular carcinoma. World J Clin Cases 2021; 9:9699-9710. [PMID: 34877309 PMCID: PMC8610931 DOI: 10.12998/wjcc.v9.i32.9699] [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: 04/18/2021] [Revised: 06/08/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains one of the most frequent types of liver cancer and is characterized by a high recurrence rate. Recent studies have proposed that long non-coding RNAs (lncRNAs) are potential biomarkers in several recurrent tumor types. It is now well understood that invasion, migration, and metastasis are important factors for tumor recurrence. Moreover, some of the known risk factors for HCC may affect the expression levels of several types of lncRNAs and thus affect the recurrence of liver cancer through lncRNA regulation. In this paper, we review the biological functions, molecular mechanisms, and roles of lncRNAs in HCC and summarize current knowledge about lncRNAs as potential biomarkers in recurrent HCC.
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Affiliation(s)
- Yuan Fang
- Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Yang Yang
- Department of Otorhinolaryngology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Na Li
- Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Xiao-Li Zhang
- Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Han-Fei Huang
- Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
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Ghafouri-Fard S, Tamizkar KH, Hussen BM, Taheri M. An update on the role of long non-coding RNAs in the pathogenesis of breast cancer. Pathol Res Pract 2021; 219:153373. [DOI: 10.1016/j.prp.2021.153373] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 01/31/2021] [Accepted: 02/03/2021] [Indexed: 12/18/2022]
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