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1
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Alluri A, Saxena P, Mishra A, Gutti RK. Association of long non-coding RNA in lipid metabolism: Implications in leukemia. Int J Biochem Cell Biol 2025; 184:106785. [PMID: 40246061 DOI: 10.1016/j.biocel.2025.106785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 04/09/2025] [Accepted: 04/15/2025] [Indexed: 04/19/2025]
Abstract
Cancer has high mortality rate and occupies second position among major diseases. Despite extensive research and therapies, in every nook and corner of the world, death rate is increasing exponentially. Hallmarks of cancer are benchmarks of cancer cells describing the fundamental principle and capabilities of the cells transforming from normal to malignant tumour. One of the major ones among them is the deregulation of cellular metabolism or metabolic reprogramming, involving alterations in glucose and lipid metabolism. Progressive research in this area has visualized the vital role of lncRNAs in lipid metabolism with respect to AML. lncRNAs involve in various cellular processes and also contribute for significant functions of the cell like chromatin remodelling, transcriptional activation and repression, gene regulation, immune response, cell differentiation, and cell cycle regulation, in addition to oncogenic processes such as proliferation, angiogenesis, migration, and apoptosis. Structural similarities are observed among mRNAs and lncRNAs in terms of poly A-tail and 5' cap however protein-coding regions are lacking. A large body of evidence has shown that lncRNAs directly or indirectly mediate lipid metabolism by activating downstream genes. Considering their potential involvement in leukemia, these lncRNAs can be explored and considered as biomarkers for therapeutics, prognosis, and diagnosis. The present review is planned to summarize the functional classification of lncRNAs, the role of lipid metabolism in cancer, different lncRNAs involved in leukemia, and different cancer types related to lipid metabolism.
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Affiliation(s)
- Anjani Alluri
- Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad, TS 500046, India
| | - Pallavi Saxena
- Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad, TS 500046, India
| | - Amit Mishra
- Department of Bioscience & Bioengineering, Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, RJ 342037, India
| | - Ravi Kumar Gutti
- Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad, TS 500046, India.
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2
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Cheng Y, Peng H, Chen Q, Xu L, Qin L. Machine learning-based transcriptmics analysis reveals BMX, GRB10, and GADD45A as crucial biomarkers and therapeutic targets in sepsis. Front Pharmacol 2025; 16:1576467. [PMID: 40230692 PMCID: PMC11994739 DOI: 10.3389/fphar.2025.1576467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Accepted: 03/18/2025] [Indexed: 04/16/2025] Open
Abstract
Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, resulting in high mortality rates and complex clinical management. This study leverages transcriptomics and machine learning (ML) to identify critical biomarkers and therapeutic targets in sepsis. Analyzing microarray data from the Gene Expression Omnibus (GEO) datasets GSE28750, GSE26440, GSE13205, and GSE9960, we discovered three pivotal biomarkers that BMX (bone marrow tyrosine kinase gene on chromosome X), GRB10 (growth factor receptor bound protein 10), and GADD45A (growth arrest and DNA damage inducible alpha), exhibiting exceptional diagnostic accuracy (AUC >0.9). Functional enrichment analyses revealed that these genes play key roles in reactive oxygen species metabolism and immune response regulation. Specifically, GADD45A was positively correlated with eosinophils and inversely associated with activated NK cells, CD8 T cells, and activated memory CD4 T cells. BMX showed positive correlations with eosinophils, mast cells, and neutrophils, while GRB10 was linked to eosinophils and M2 macrophages. Additionally, we constructed a comprehensive mRNA-miRNA-lncRNA regulatory network, identifying key interactions that may drive sepsis pathogenesis. Molecular docking and dynamics simulations validated Bendroflumethiazide, Cianidanol, and Hexamidine as promising therapeutic agents targeting these biomarkers. In conclusion, this integrated approach provides profound insights into the molecular mechanisms underlying sepsis, pinpointing BMX, GRB10, and GADD45A as pivotal biomarkers and therapeutic targets. These findings significantly enhance our understanding of sepsis pathophysiology and lay the groundwork for developing personalized diagnostic and therapeutic strategies aimed at improving patient outcomes.
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Affiliation(s)
- Yanwei Cheng
- Department of Emergency, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, China
| | - Haoran Peng
- Department of Neurology, People’s Hospital of Henan University, Henan Provincial People’s Hospital, Zhengzhou, Henan, China
| | - Qiao Chen
- Nursing Department, Air Force Medical Center, PLA, Beijing, China
| | - Lijun Xu
- Department of Emergency, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, China
| | - Lijie Qin
- Department of Emergency, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, China
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Sharma S. Unraveling the role of long non-coding RNAs in therapeutic resistance in acute myeloid leukemia: New prospects & challenges. Noncoding RNA Res 2024; 9:1203-1221. [PMID: 39036603 PMCID: PMC11259994 DOI: 10.1016/j.ncrna.2024.05.009] [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: 02/12/2024] [Revised: 05/19/2024] [Accepted: 05/20/2024] [Indexed: 07/23/2024] Open
Abstract
Acute Myeloid Leukemia (AML) is a fatal hematological disease characterized by the unchecked proliferation of immature myeloid blasts in different tissues developed by various mutations in hematopoiesis. Despite intense chemotherapeutic regimens, patients often experience poor outcomes, leading to substandard remission rates. In recent years, long non-coding RNAs (lncRNAs) have increasingly become important prognostic and therapeutic hotspots, due to their contributions to dysregulating many functional epigenetic, transcriptional, and post-translational mechanisms leading to alterations in cell expressions, resulting in increased chemoresistance and reduced apoptosis in leukemic cells. Through this review, I highlight and discuss the latest advances in understanding the major mechanisms through which lncRNAs confer therapy resistance in AML. In addition, I also provide perspective on the current strategies to target lncRNA expressions. A better knowledge of the critical role that lncRNAs play in controlling treatment outcomes in AML will help improve existing medications and devise new ones.
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Affiliation(s)
- Siddhant Sharma
- Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada
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Qian Y, Yang L, Chen J, Zhou C, Zong N, Geng Y, Xia S, Yang H, Bao X, Chen Y, Xu Y. SRGN amplifies microglia-mediated neuroinflammation and exacerbates ischemic brain injury. J Neuroinflammation 2024; 21:35. [PMID: 38287411 PMCID: PMC10826034 DOI: 10.1186/s12974-024-03026-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 01/19/2024] [Indexed: 01/31/2024] Open
Abstract
BACKGROUND Microglia is the major contributor of post-stroke neuroinflammation cascade and the crucial cellular target for the treatment of ischemic stroke. Currently, the endogenous mechanism underlying microglial activation following ischemic stroke remains elusive. Serglycin (SRGN) is a proteoglycan expressed in immune cells. Up to now, the role of SRGN on microglial activation and ischemic stroke is largely unexplored. METHODS Srgn knockout (KO), Cd44-KO and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO) to mimic ischemic stroke. Exogenous SRGN supplementation was achieved by stereotactic injection of recombinant mouse SRGN (rSRGN). Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological functions were evaluated by the modified neurological severity score (mNSS) and grip strength. Microglial activation was detected by Iba1 immunostaining, morphological analysis and cytokines' production. Neuronal death was examined by MAP2 immunostaining and FJB staining. RESULTS The expression of SRGN and its receptor CD44 was significantly elevated in the ischemic mouse brains, especially in microglia. In addition, lipopolysaccharide (LPS) induced SRGN upregulation in microglia in vitro. rSRGN worsened ischemic brain injury in mice and amplified post-stroke neuroinflammation, while gene knockout of Srgn exerted reverse impacts. rSRGN promoted microglial proinflammatory activation both in vivo and in vitro, whereas Srgn-deficiency alleviated microglia-mediated inflammatory response. Moreover, the genetic deletion of Cd44 partially rescued rSRGN-induced excessed neuroinflammation and ischemic brain injury in mice. Mechanistically, SRGN boosted the activation of NF-κB signal, and increased glycolysis in microglia. CONCLUSION SRGN acts as a novel therapeutic target in microglia-boosted proinflammatory response following ischemic stroke.
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Affiliation(s)
- Yi Qian
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Lixuan Yang
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Jian Chen
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Chao Zhou
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Ningning Zong
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Yang Geng
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Shengnan Xia
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Haiyan Yang
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Xinyu Bao
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Yan Chen
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Yun Xu
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
- Department of Neurology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, 210008, China.
- Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, 210008, China.
- Jiangsu Provincial Key Discipline of Neurology, Nanjing, 210008, China.
- Nanjing Neurology Medical Center, Nanjing, 210008, China.
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Zhou Q, Shu X, Chai Y, Liu W, Li Z, Xi Y. The non-coding competing endogenous RNAs in acute myeloid leukemia: biological and clinical implications. Biomed Pharmacother 2023; 163:114807. [PMID: 37150037 DOI: 10.1016/j.biopha.2023.114807] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 04/28/2023] [Accepted: 04/30/2023] [Indexed: 05/09/2023] Open
Abstract
Acute myeloid leukemia (AML) is a hematologic carcinoma that has seen a considerable improvement in patient prognosis because of genetic diagnostics and molecularly-targeted therapies. Nevertheless, recurrence and drug resistance remain significant obstacles to leukemia treatment. It is critical to investigate the underlying molecular mechanisms and find solutions. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), circular RNAs, long non-coding RNAs, and pseudogenes, have been found to be crucial components in driving cancer. The competing endogenous RNA (ceRNA) mechanism has expanded the complexity of miRNA-mediated gene regulation. A great deal of literature has shown that ncRNAs are essential to the biological functions of the ceRNA network (ceRNET). NcRNAs can compete for the same miRNA response elements to influence miRNA-target RNA interactions. Recent evidence suggests that ceRNA might be a potential biomarker and therapeutic strategy. So far, however, there have been no comprehensive studies on ceRNET about AML. What is not yet clear is the clinical application of ceRNA in AML. This study attempts to summarize the development of research on the related ceRNAs in AML and the roles of ncRNAs in ceRNET. We also briefly describe the mechanisms of ceRNA and ceRNET. What's more significant is that we explore the clinical value of ceRNAs to provide accurate diagnostic and prognostic biomarkers as well as therapeutic targets. Finally, limitations and prospects are considered.
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Affiliation(s)
- Qi Zhou
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Xiaojun Shu
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China; Department of Vascular Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Yihong Chai
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Wenling Liu
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Zijian Li
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China; Department of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Yaming Xi
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China; Department of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
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Yao Q, Zhang L, Liu Z, Yu L, Wang Y, Liu J, Wang Y. LncRNA MAFG-AS1-induced acute myeloid leukemia development via modulating miR-147b/HOXA9. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:19250-19258. [PMID: 36229729 DOI: 10.1007/s11356-022-23537-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 02/22/2021] [Indexed: 06/16/2023]
Abstract
Recent references discovered that lncRNAs acted roles in malignant cancer development. However, the role of MAFG-AS1 in acute myeloid leukemia (AML) development remains unknown. MAFG-AS1 and miR-147b were determined in AML cells and specimens using qRT-PCR assay. Cell proliferation was detected by CCK-8 analysis and flow cytometry was carried out to measure cell cycle. Luciferase reporter analysis was done to determine the mechanism of MAFG-AS1 and miR-147b. We noted that MAFG-AS1 was overexpressed in AML cells and in serum and bone narrow from AML compared with normal controls specimen. Elevated expression of MAFG-AS1 increased cell growth, cycle and EMT in AML cell HL-60 cell. MAFG-AS1 sponged miR-147b expression in HL-60 cell. Moreover, miR-147b was downregulated in AML cells and in serum and bone narrow from AML compared with normal control specimen. miR-147b was negatively correlated with MAFG-AS1 in the serum and bone narrow of AML cases. We illustrated that HOXA9 was one target of miR-147b and ectopic expression of MAFG-AS1 enhanced HOXA9 expression HL-60 cell. Forced expression of MAFG-AS1 induced cell growth, cycle, and EMT via promoting HOXA9. These data illustrated that MAFG-AS1 acted as one oncogenic gene and accelerated AML progression via modulating miR-147b/HOXA9 axis.
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Affiliation(s)
- Qiying Yao
- College of Basic Medical Sciences, Dalian Medical University, Dalian, 116027, Liaoning, China
| | - Li Zhang
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Zhengjuan Liu
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Lei Yu
- Department of Infectious Disease, The Fourth Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China
| | - Yuchuan Wang
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Junli Liu
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Yingjie Wang
- Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China.
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7
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Rahmati A, Mafi A, Soleymani F, Babaei Aghdam Z, Masihipour N, Ghezelbash B, Asemi R, Aschner M, Vakili O, Homayoonfal M, Asemi Z, Sharifi M, Azadi A, Mirzaei H, Aghadavod E. Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia. Front Oncol 2023; 13:1149187. [PMID: 37124518 PMCID: PMC10140500 DOI: 10.3389/fonc.2023.1149187] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/29/2023] [Indexed: 05/02/2023] Open
Abstract
Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.
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Affiliation(s)
- Atefe Rahmati
- Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Basic Sciences, Faculty of Medicine, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Firooze Soleymani
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Babaei Aghdam
- Imaging Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Niloufar Masihipour
- Department of Medicine, Lorestan University of Medical Science, Lorestan, Iran
| | - Behrooz Ghezelbash
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Asemi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Homayoonfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Mehran Sharifi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abbas Azadi
- Department of Internal Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- *Correspondence: Abbas Azadi, ; Esmat Aghadavod, ; Hamed Mirzaei, ;
| | - Esmat Aghadavod
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- Department of Clinical Biochemistry, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- *Correspondence: Abbas Azadi, ; Esmat Aghadavod, ; Hamed Mirzaei, ;
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Hiraoka M, Takashima S, Wakihara Y, Kamatari YO, Shimizu K, Okada A, Inoshima Y. Identification of Potential mRNA Biomarkers in Milk Small Extracellular Vesicles of Enzootic Bovine Leukosis Cattle. Viruses 2022; 14:1022. [PMID: 35632763 PMCID: PMC9146096 DOI: 10.3390/v14051022] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/03/2022] [Accepted: 05/09/2022] [Indexed: 01/27/2023] Open
Abstract
Enzootic bovine leukosis (EBL) is a disease caused by bovine leukemia virus (BLV); only a small percentage of BLV-infected cattle develop EBL and present with B-cell lymphosarcoma. There is no vaccine against BLV, treatment for EBL, or method for predicting the possibility of EBL onset, thus making EBL control difficult. Herein, to explore biomarkers for EBL in milk, we examined the mRNA profiles of small extracellular vesicles (sEVs) in milk from four BLV-uninfected and four EBL cattle by microarray analysis. It was revealed that 14 mRNAs were encapsulated in significantly higher quantities, and these mRNAs were therefore selected as biomarker candidates. Primers for these mRNAs were designed, and nine primer sets were available for quantitative real-time PCR. Nine mRNAs were evaluated for their availability as biomarkers for EBL using sEVs from newly-collected milk of 7 uninfected and 10 EBL cattle. The quantities of eight mRNAs (TMEM156, SRGN, CXCL8, DEFB4A, FABP5, LAPTM5, LGALS1, and VIM) were significantly higher in milk sEVs of EBL cattle than in those of uninfected cattle. Therefore, our findings indicate that these eight mRNAs in milk sEVs can be used as potential EBL biomarkers with combination use, although single mRNA use is not enough. Consequently, cattle at risk of EBL onset can be identified by monitoring the fluctuation in quantities of these mRNAs in milk before they develop EBL.
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Affiliation(s)
- Mami Hiraoka
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; (M.H.); (K.S.); (A.O.)
| | - Shigeo Takashima
- Division of Genomics Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; (S.T.); (Y.W.)
| | - Yoshiko Wakihara
- Division of Genomics Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; (S.T.); (Y.W.)
| | - Yuji O. Kamatari
- Division of Instrumental Analysis, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan;
| | - Kaori Shimizu
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; (M.H.); (K.S.); (A.O.)
| | - Ayaka Okada
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; (M.H.); (K.S.); (A.O.)
- Education and Research Center for Food Animal Health, Gifu University (GeFAH), 1-1 Yanagido, Gifu 501-1193, Japan
| | - Yasuo Inoshima
- Laboratory of Food and Environmental Hygiene, Cooperative Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; (M.H.); (K.S.); (A.O.)
- Education and Research Center for Food Animal Health, Gifu University (GeFAH), 1-1 Yanagido, Gifu 501-1193, Japan
- The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
- Joint Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
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9
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Wang Y, Chen X, Lu Z, Lai C. Circ_0093887 regulated ox-LDL induced human aortic endothelial cells viability, apoptosis, and inflammation through modulating miR-758-3p/BAMBI axis in atherosclerosis. Clin Hemorheol Microcirc 2022; 81:343-358. [PMID: 35527543 DOI: 10.3233/ch-221445] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND: Compelling evidence demonstrated that circular RNAs (circRNAs) were involved in the progression of atherosclerosis (AS). However, the role of circ_0093887 in the progression of AS is unclear. The purpose of this study was to explore the role and mechanism of circ_0093887 in oxidized-low density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs). METHODS: HAECs were stimulated by ox-LDL to simulate AS-like injury in vitro. Circ_0093887, microRNA-758-3p (miR-758-3p), and BMP And Activin Membrane-Bound Inhibitor (BAMBI) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). PCNA, Bax, Bcl-2, and BAMBI protein levels were detected by western blot. Cell viability and apoptosis were examined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Tube formation assay was used to assess tube formation. The levels of inflammatory factors TNF-α and IL-1β were detected by corresponding ELISA kits. The relationship between miR-758-3p and circ_0093887 or BAMBI was tested via dual-luciferase reporter analysis and RNA immunoprecipitation. Oxidative stress related indexes (ROS and MDA) were detected by corresponding kits. RESULTS: The expression levels of circ_0093887 and BAMBI were prominently downregulated in ox-LDL-induced HAECs compared with control, whereas the expression of miR-758-3p was upregulated. Overexpression of circ_0093887 promoted HAECs viability and tube formation, and restrained cell apoptosis in ox-LDL-induced HAECs compared with untreated HAECs. Mechanistically, circ_0093887 regulated the expression of BAMBI through miR-758-3p. Further experiments showed that upregulation of miR-758-3p reversed changes in cell function induced by circ_0093887. In addition, reduced BAMBI salvaged miR-758-3p knockdown mediated effects on cell function. CONCLUSION: Circ_0093887 demonstrated its diagnostic and therapeutic value in AS by promoting the role of the miR-758-3p/BAMBI axis in the ox-LDL-induced endothelial injury of HAECs.
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Affiliation(s)
- Yueru Wang
- Department of Internal Medicine-Cardiovascular, Shanxi Provincial People’s Hospital, Taiyuan City, Shanxi Province, China
| | - Xiaoyan Chen
- Department of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province, China
| | - Zhikai Lu
- Department of CT Room, General Hospital of Tisco (Sixth Hospital of Shanxi Medical University), Taiyuan City, Shanxi Province, China
| | - Chunlin Lai
- Department of Internal Medicine-Cardiovascular, Shanxi Provincial People’s Hospital, Taiyuan City, Shanxi Province, China
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10
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Shan DD, Zheng QX, Wang J, Chen Z. Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression. World J Gastroenterol 2022; 28:1641-1655. [PMID: 35581965 PMCID: PMC9048787 DOI: 10.3748/wjg.v28.i16.1641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/09/2022] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.
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Affiliation(s)
- Dan-Dan Shan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qiu-Xian Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Jing Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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11
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Wang D, Zou L, Luo J, Zhang C, Feng H, Qin G. Potential diagnostic and prognostic value of the long non-coding RNA SNHG3 in human cancers: A systematic review and meta-analysis. Int J Biol Markers 2022; 37:3-12. [PMID: 35130083 DOI: 10.1177/03936155221077121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Small nucleolar RNA host gene 3 (SNHG3), as a novel long non-coding RNA (lncRNA) participates in the oncogenic processes of various cancers. We combined a systematic review and a meta-analysis to assess the potential role of SNHG3 as a pan-cancer marker for cancer diagnosis and prognosis. METHODS Our study comprehensively searched for SNHG3 expression profiling studies from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, Google Scholar, and The Cancer Genome Atlas (TCGA). The diagnostic capacity of SNHG3 for all cancers in TCGA database was evaluated from the perspective of pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve. Also, this research studied the correlation of SNHG3 expression and the overall survival to access its prognostic value. RESULTS A sum total of 11,888 cancer patients and 730 controls from 44 eligible studies were enrolled in this integrated analysis. In TCGA database, SNHG3 was significantly upregulated in most types of cancers (16/33, 48%). The pooled sensitivity, specificity, and DOR with 95% CIs was 0.72 (95% CI: 0.60-0.82), 0.87 (95% CI: 0.84-0.90), and 18 (95% CI: 11-30), respectively. Similarly, the AUC of the sROC curve was 0.89 (95% CI: 0.86-0.92), indicating SNHG3 was highly conserved as a diagnosis biomarker. Additionally, SNHG3 overexpression significantly deteriorated the overall survival of cancer patients (pooled HR = 1.28, 95% CI:1.11-1.48; P < 0.05). CONCLUSIONS These findings suggest that the lncRNA SNHG3 could serve as a promising diagnostic and prognostic biomarker.
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Affiliation(s)
- Dingting Wang
- Department of Otolaryngology Head and Neck Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Longfei Zou
- Department of Orthopedic Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jian Luo
- Department of Otolaryngology Head and Neck Surgery, The First People's Hospital of Yibin, Yibin, China
| | - Conghong Zhang
- Department of Otolaryngology Head and Neck Surgery, Sichuan Province Panzhihua Central Hospital, Panzhihua, China * These authors contributed equally to this work
| | - Huajun Feng
- Department of Otolaryngology Head and Neck Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Gang Qin
- Department of Otolaryngology Head and Neck Surgery, 556508Affiliated Hospital of Southwest Medical University, Luzhou, China
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12
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Xi X, Hu Z, Wu Q, Hu K, Cao Z, Zhou J, Liao J, Zhang Z, Hu Y, Zhong X, Bao Y. High expression of small nucleolar RNA host gene 3 predicts poor prognosis and promotes bone metastasis in prostate cancer by activating transforming growth factor-beta signaling. Bioengineered 2022; 13:1895-1907. [PMID: 35030969 PMCID: PMC8805939 DOI: 10.1080/21655979.2021.2020393] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Bone metastasis is closely related to tumor death in prostate cancer (PC). Long noncoding RNA small nucleolar RNA host gene 3 (SNHG3) has been implicated in the initiation and progression of multiple human cancers. Nevertheless, the biological function of SNHG3 in PC has not been elucidated. Our results indicated that SNHG3 was upregulated in bone metastasis-positive PC tissues compared to bone metastasis-negative PC tissues and adjacent normal tissues. High expression of SNHG3 indicates advanced clinicopathological features and predicts poor prognosis in patients with PC. Meanwhile, SNHG3 knockdown suppressed the proliferation, migration, and invasion abilities of PC cells and inhibited PC cell metastasis to the bone. Mechanistically, SNHG3 enhanced the expression of transforming growth factor beta receptor 1 (TGFBR1) and activated transforming growth factor-Beta (TGF-β) signaling by targeting miR-214-3p. Our study demonstrated the novel role of the SNHG3/miR-214-3p/TGF-β axis in tumor growth and bone metastasis in PC, indicating that SNHG3 may act as a biomarker and promising therapeutic target against PC.
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Affiliation(s)
- Xinhua Xi
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Zhengbo Hu
- Department of Orthopedics, Shaoguan First People's Hospital Affiliated Southern Medical University, Shaoguan, Guangdong, China
| | - Qiang Wu
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Konghe Hu
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Zhengguo Cao
- Department of Urology, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Jun Zhou
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Junjian Liao
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Zhipeng Zhang
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Yongyu Hu
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Xueren Zhong
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
| | - Yongzheng Bao
- Department of Orthopaedics, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China
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13
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A diagnostic and prognostic value of blood-based circulating long non-coding RNAs in Thyroid, Pancreatic and Ovarian Cancer. Crit Rev Oncol Hematol 2022; 171:103598. [PMID: 35033662 DOI: 10.1016/j.critrevonc.2022.103598] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 12/12/2022] Open
Abstract
Several studies have demonstrated the potential of circulating long non-coding RNAs (lncRNAs) as promising cancer biomarkers. Herein, we addressed the regulatory role of circulating lncRNAs and their potential value as diagnostic/prognostic markers for thyroid, pancreatic and ovarian cancers. Furthermore, we analyzed and measured the clinical implications and association of lncRNAs with sensitivity, specificity, and area under the ROC curve (AUC). Based on our meta-analysis, we found that GAS8-AS1 could discriminate thyroid cancer from non-cancer and other cancers with higher accuracy (AUC = 0.746; sensitivity = 61.70%, and specificity = 90.00%). Similarly, for ovarian cancer, lncRNA RP5-837J1.2 was found to have ideal diagnostic potential with critical clinical specifications of AUC = 0.996; sensitivity = 97.30% and specificity = 94.60%. Whereas we could not find any lncRNA having high diagnostic/prognostic efficiency in pancreatic cancer. We believe that lncRNAs mentioned above may explore clinical settings for the diagnosis and prognosis of cancer patients.
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14
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Kirtonia A, Ashrafizadeh M, Zarrabi A, Hushmandi K, Zabolian A, Bejandi AK, Rani R, Pandey AK, Baligar P, Kumar V, Das BC, Garg M. Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia. J Cell Physiol 2021; 237:450-465. [PMID: 34569616 DOI: 10.1002/jcp.30590] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 08/10/2021] [Accepted: 09/01/2021] [Indexed: 12/19/2022]
Abstract
Acute myeloid leukemia (AML) is a common hematological disorder with heterogeneous nature that resulted from blocked myeloid differentiation and an enhanced number of immature myeloid progenitors. During several decades, different factors, including cytogenetic, genetic, and epigenetic have been reported to contribute to the pathogenesis of AML by inhibiting the differentiation and ensuring the proliferation of myeloid blast cells. Recently, long noncoding RNAs (lncRNAs) have been considered as potential diagnostic, therapeutic, and prognostic factors in different human malignancies including AML. Altered expression of lncRNAs is correlated with the transformation of hematopoietic stem and progenitor cells into leukemic blast cells because of their distinct role in the key cellular processes. We discuss the significant role of lncRNAs in the proliferation, survival, differentiation, leukemic stem cells in AML and their involvement in different molecular pathways (insulin-like growth factor type I receptor, FLT3, c-KIT, Wnt, phosphatidylinositol 3-kinase/protein kinase-B, microRNAs), and associated mechanisms such as autophagy, apoptosis, and glucose metabolism. In addition, we aim to highlight the role of lncRNAs as reliable biomarkers for diagnosis, prognosis, and drug resistance for precision medicine in AML.
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Affiliation(s)
- Anuradha Kirtonia
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, India
| | - Milad Ashrafizadeh
- Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Tuzla, Istanbul, Turkey.,Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul, Turkey
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul, Turkey.,Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer, Istanbul, Turkey
| | - Kiavash Hushmandi
- Division of Epidemiology and Zoonoses, Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Amirhossein Zabolian
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Atefe K Bejandi
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Reshma Rani
- Amity Institute of Biotechnology (AIB), Amity University, Noida, Uttar Pradesh, India
| | - Amit K Pandey
- Amity Institute of Biotechnology (AIB), Amity University, Gurgaon, Haryana, India
| | - Prakash Baligar
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, India
| | - Vinit Kumar
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, India
| | - Bhudev C Das
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, India
| | - Manoj Garg
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh, India
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15
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Tian X, Shen L, Wang Z, Zhou L, Peng L. A novel lncRNA-protein interaction prediction method based on deep forest with cascade forest structure. Sci Rep 2021; 11:18881. [PMID: 34556758 PMCID: PMC8460650 DOI: 10.1038/s41598-021-98277-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 08/18/2021] [Indexed: 02/08/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) regulate many biological processes by interacting with corresponding RNA-binding proteins. The identification of lncRNA-protein Interactions (LPIs) is significantly important to well characterize the biological functions and mechanisms of lncRNAs. Existing computational methods have been effectively applied to LPI prediction. However, the majority of them were evaluated only on one LPI dataset, thereby resulting in prediction bias. More importantly, part of models did not discover possible LPIs for new lncRNAs (or proteins). In addition, the prediction performance remains limited. To solve with the above problems, in this study, we develop a Deep Forest-based LPI prediction method (LPIDF). First, five LPI datasets are obtained and the corresponding sequence information of lncRNAs and proteins are collected. Second, features of lncRNAs and proteins are constructed based on four-nucleotide composition and BioSeq2vec with encoder-decoder structure, respectively. Finally, a deep forest model with cascade forest structure is developed to find new LPIs. We compare LPIDF with four classical association prediction models based on three fivefold cross validations on lncRNAs, proteins, and LPIs. LPIDF obtains better average AUCs of 0.9012, 0.6937 and 0.9457, and the best average AUPRs of 0.9022, 0.6860, and 0.9382, respectively, for the three CVs, significantly outperforming other methods. The results show that the lncRNA FTX may interact with the protein P35637 and needs further validation.
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Affiliation(s)
- Xiongfei Tian
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China
| | - Ling Shen
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China
| | - Zhenwu Wang
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China
| | - Liqian Zhou
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China.
| | - Lihong Peng
- School of Computer Science, Hunan University of Technology, Zhuzhou, 412007, China.
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16
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LINC00987 knockdown inhibits the progression of acute myeloid leukemia by suppressing IGF2BP2-mediated PA2G4 expression. Anticancer Drugs 2021; 33:e207-e217. [PMID: 34407052 DOI: 10.1097/cad.0000000000001188] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
This study aimed to investigate the role and potential mechanisms of LINC00987 in acute myeloid leukemia (AML) progression. The expression of LINC00987 in bone marrow specimens of AML patients and cell lines was measured by quantitative reverse transcription PCR (RT-qPCR). Small interfering RNA targeting LINC00987 (si-LINC00987) was transfected into AML cell lines HL-60 and KG-1, and the proliferation, invasion and apoptosis were detected with Cell Counting Kit-8 (CCK-8), Transwell and flow cytometry, respectively. Moreover, the binding between LINC00987 and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was validated with an RNA pull-down assay. Co-immunoprecipitation assay was used to verify the binding between IGF2BP2 and proliferation-associated 2G4 (PA2G4). Then rescue experiments were performed to explore the effects of LINC00987/IGF2BP2/PA2G4 axis on HL-60 and KG-1 cell functions. Additionally, HL-60 cells transfected with si-LINC00987 were injected into mice, followed by the evaluation of xenograft tumor growth. LINC00987 was upregulated in AML patient specimens and cell lines. LINC00987 knockdown inhibited proliferation and invasion and promoted apoptosis in AML cells. LINC00987 could bind with IGF2BP2 and promote its expression, and IGF2BP2 overexpression reversed the effects of LINC00987 knockdown on the proliferation, invasion and apoptosis in AML cells. Besides, IGF2BP2 could bind with PA2G4. IGF2BP2 knockdown inhibited proliferation and invasion, and promoted apoptosis in AML cells, whereas PA2G4 overexpression reversed these effects. Additionally, the LINC00987 knockdown inhibited the xenograft tumor growth of AML in vivo. Knockdown of LINC00987 inhibits AML cell proliferation and invasion, and promotes apoptosis in vitro and reduces tumor growth in vivo by suppressing IGF2BP2-mediated PA2G4 expression.
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17
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Lei W, Lin J, Liu F, Chen N. Long noncoding RNA GAS6 antisense RNA1 silencing attenuates the tumorigenesis of acute myeloid leukemia cells through targeting microRNA-370-3p/Tetraspanin3 axis. Clin Hemorheol Microcirc 2021; 78:69-81. [PMID: 33523043 DOI: 10.3233/ch-201039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE Acute myeloid leukemia (AML) is a type of hematologic malignancy. This study was attempt to explore the effect of long noncoding RNA GAS6 antisense RNA1 (GAS6-AS1) on pediatric AML and the regulation mechanisms. METHODS GAS6-AS1, microRNA-370-3p (miR-370-3p), and Tetraspanin3 (TSPAN3) expression in bone marrow (BM) tissues and cells was determined by qRT-PCR. The correlation between GAS6-AS1 and clinicopathological features of pediatric patients with AML was assessed. In vitro, viability and migration and invasion of AML cells were evaluated via MTT and transwell assays, respectively. Interactions among GAS6-AS1, miR-370-3p, and TSPAN3 were revealed by dual-luciferase reporter assays. Western blot was applied to confirm the protein expression of TSPAN3. RESULTS GAS6-AS1 and TSPAN3 expression was elevated in BM tissues of pediatric patients with AML and AML cells, but miR-370-3p expression was reduced. GAS6-AS1 expression was positively related to French-American-British (FAB) classification in pediatric patients with AML. In vitro, GAS6-AS1 deficiency restrained the viability, migration, and invasion of AML cells. Additionally, GAS6-AS1 mediated miR-370-3p expression indeed and TSPAN3 was identified as a target of miR-370-3p. Furthermore, miR-370-3p overexpression repressed the protein expression of TSPAN3. The feedback experiments demonstrated that miR-370-3p inhibition or TSPAN3 overexpression mitigated the suppressive effect of sh-GAS6-AS1 on the tumorigenesis of AML cells. CONCLUSION GAS6-AS1 silencing restrained AML cell viability, migration, and invasion by targeting miR-370-3p/TSPAN3 axis, affording a novel therapeutic target for pediatric AML.
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Affiliation(s)
- Weijuan Lei
- Department of Pediatrics, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China
| | - Juanjuan Lin
- Department of Pediatrics, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China
| | - Fang Liu
- Department of Pediatrics, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China
| | - Nina Chen
- Department of Pediatrics, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China
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18
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Guo X, Zheng J, Yu MJ, Piao HZ, Zhao HY. Long noncoding RNA SNHG3 promotes glioma tumorigenesis by sponging miR-485-5p to upregulate LMX1B expression. Kaohsiung J Med Sci 2021; 37:851-862. [PMID: 34153159 DOI: 10.1002/kjm2.12411] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 04/07/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
LIM homeobox transcription factor 1-beta (LMX1B) has recently been found to be highly expressed in advanced gliomas and is associated with poor survival. However, the regulatory molecular mechanism of LMX1B expression in gliomas remains unclear. In this study, bioinformatics analysis showed that miR-485-5p may be the potential upstream regulator of LMX1B, and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) may function as a competitive endogenous RNA to sponge miR-485-5p. In addition, the expression of SNHG3 and LMX1B in advanced glioma tissues was significantly upregulated, while the expression of miR-485-5p was significantly downregulated. SNHG3 overexpression reduced the expression of miR-485-5p; increased the expression of LMX1B; and promoted the proliferation, migration, and invasion of glioma cells. In contrast, miR-485-5p overexpression reduced the expression of LMX1B and inhibited cell proliferation, migration, and invasion. The luciferase reporter assay and RNA immunoprecipitation assay further confirmed the interaction between SNHG3 and miR-485-5p and between miR-485-5p and LMX1B. In addition, subcutaneous and orthotropic xenograft models confirmed that lncRNA SNHG3 silencing or miR-485-5p overexpression significantly reduced the growth of glioma xenografts and prolonged survival time. These results indicate that lncRNA SNHG3 can regulate the expression of LMX1B by sponging miR-485-5p, thereby promoting the proliferation, migration, and invasion of glioma cells. This study provides the first evidence that the SNHG3/miR-485-5p/LMX1B axis is involved in glioma tumorigenesis and highlights the potential of SNHG3 and miR-485-5p as therapeutic targets for glioma.
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Affiliation(s)
- Xu Guo
- Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Jian Zheng
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ming-Jun Yu
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hao-Zhe Piao
- Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Hong-Yu Zhao
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China
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Zhu ZJ, Pang Y, Jin G, Zhang HY, Wang WH, Liu JW, Tuo GX, Wu P, Yang Y, Wang ZQ, Wang K. Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis. Aging (Albany NY) 2021; 13:17155-17176. [PMID: 34081626 PMCID: PMC8312407 DOI: 10.18632/aging.203062] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 03/14/2021] [Indexed: 04/10/2023]
Abstract
Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.
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Affiliation(s)
- Zi-Jiang Zhu
- Department of Thoracic Surgery 2, Gansu Provincial People's Hospital, Lanzhou 730000, China
| | - Yao Pang
- Department of Thoracic Surgery 2, Gansu Provincial People's Hospital, Lanzhou 730000, China
| | - Gang Jin
- Department of Thoracic Surgery 2, Gansu Provincial People's Hospital, Lanzhou 730000, China
| | - Hong-Yi Zhang
- Department of Thoracic Surgery 2, Gansu Provincial People's Hospital, Lanzhou 730000, China
| | - Wen-Hao Wang
- Department of Thoracic Surgery 2, Gansu Provincial People's Hospital, Lanzhou 730000, China
| | - Jia-Wei Liu
- Department of Thoracic Surgery 2, Gansu Provincial People's Hospital, Lanzhou 730000, China
| | - Guang-Xin Tuo
- School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
| | - Peng Wu
- School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
| | - Yi Yang
- School of Clinical Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
| | - Ze-Quan Wang
- School of Clinical Medicine, Ningxia Medical University, Ningxia 750004, China
| | - Kui Wang
- School of Clinical Medicine, Ningxia Medical University, Ningxia 750004, China
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Identification of Potential Key lncRNAs in the Context of Mouse Myeloid Differentiation by Systematic Transcriptomics Analysis. Genes (Basel) 2021; 12:genes12050630. [PMID: 33922442 PMCID: PMC8146222 DOI: 10.3390/genes12050630] [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: 02/20/2021] [Revised: 04/09/2021] [Accepted: 04/21/2021] [Indexed: 11/17/2022] Open
Abstract
Hematopoietic differentiation is a well-orchestrated process by many regulators such as transcription factor and long non-coding RNAs (lncRNAs). However, due to the large number of lncRNAs and the difficulty in determining their roles, the study of lncRNAs is a considerable challenge in hematopoietic differentiation. Here, through gene co-expression network analysis over RNA-seq data generated from representative types of mouse myeloid cells, we obtained a catalog of potential key lncRNAs in the context of mouse myeloid differentiation. Then, employing a widely used in vitro cell model, we screened a novel lncRNA, named Gdal1 (Granulocytic differentiation associated lncRNA 1), from this list and demonstrated that Gdal1 was required for granulocytic differentiation. Furthermore, knockdown of Cebpe, a principal transcription factor of granulocytic differentiation regulation, led to down-regulation of Gdal1, but not vice versa. In addition, expression of genes involved in myeloid differentiation and its regulation, such as Cebpa, were influenced in Gdal1 knockdown cells with differentiation blockage. We thus systematically identified myeloid differentiation associated lncRNAs and substantiated the identification by investigation of one of these lncRNAs on cellular phenotype and gene regulation levels. This study promotes our understanding of the regulation of myeloid differentiation and the characterization of roles of lncRNAs in hematopoietic system.
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Overexpression of lncRNA SNGH3 Predicts Unfavorable Prognosis and Clinical Outcomes in Human Cancers: Evidence from a Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2021; 2020:7974034. [PMID: 32802874 PMCID: PMC7335396 DOI: 10.1155/2020/7974034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 05/23/2020] [Accepted: 05/28/2020] [Indexed: 12/22/2022]
Abstract
Long noncoding RNAs (lncRNAs) have been confirmed to play a crucial role in human disease, especially in tumor development and progression. Small nucleolar RNA host gene (SNHG3), a newly identified lncRNA, has been found dysregulated in various cancers. Nevertheless, the results remain controversial. Thus, we aim to analyze the comprehensive data to elaborate the association between SNHG3 expression and clinical outcomes in multiple cancers. We searched PubMed, Web of Science, Cochrane Library, Embase, and MEDLINE database to identify eligible articles. STATA software was applied to calculate the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (95% CI) for survival outcomes and clinical parameters, respectively. Besides, the data from The Cancer Genome Atlas (TCGA) dataset was extracted to verify the results in our meta-analysis. There were thirteen studies totaling 919 cancer patients involved in this meta-analysis. The results demonstrated that high SNHG3 expression was significantly associated with poor overall survival (OS) (HR = 2.53, 95% CI: 1.94-3.31) in cancers, disease-free survival (DFS) (HR = 3.89, 95% CI: 1.34-11.3), and recurrence-free survival (RFS) (HR = 2.42, 95% CI: 1.14-5.15) in hepatocellular carcinoma. Analysis stratified by analysis method, sample size, follow-up time, and cancer type further verified the prognostic value of SNHG3. Additionally, patients with high SNHG3 expression tended to have more advanced clinical stage, higher histological grade, earlier distant metastasis, and earlier lymph node metastasis. Excavation of TCGA dataset valuated that SNHG3 was upregulated in various cancers and predicted worse OS and DFS. Overexpressed SNHG3 was strongly associated with poor survival and clinical outcomes in human cancers and therefore can serve as a promising biomarker for predicting patients' prognosis.
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LINC00221 suppresses the malignancy of children acute lymphoblastic leukemia. Biosci Rep 2021; 40:222665. [PMID: 32297639 PMCID: PMC7199449 DOI: 10.1042/bsr20194070] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 04/08/2020] [Accepted: 04/14/2020] [Indexed: 11/21/2022] Open
Abstract
As the most common malignant disease in childhood, children acute lymphoblastic leukemia (ALL) is a heterogeneous disease caused by the accumulated genetic alterations. Long non-coding RNAs (lncRNAs) are reported as critical regulators in diseases. GEPIA database indicated that long intergenic non-protein coding RNA 221 (LINC00221) was conspicuously down-regulated in acute myeloid leukemia. However, its expression pattern in ALL has not been revealed. This work was carried out to study the role of LINC00221 in ALL cells. Quantitative real-time PCR (qRT-PCR) quantified LINC00221 expression in ALL cells. The function of LINC00221 in ALL was determined by ki-67 immunofluorescence staining, EdU, TUNEL, JC-1, and caspase-3/8/9 activity assays. RNA pull down and Ago2-RNA immunoprecipitation (RIP) assays investigated the interaction between miR-152-3p and LINC00221 or ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2). Our study revealed the low expression of LINC00221 in ALL cells. Subsequently, LINC00221 was verified to bind with miR-152-3p. Moreover, functional assays pointed out that LINC00221 overexpression posed anti-proliferation and pro-apoptosis effects in ALL cells, and these effects could be separately reversed by miR-152-3p up-regulation. Afterward, LINC00221 was revealed to regulate ATP2A2 expression via sponging miR-152-3p. Additionally, ATP2A2 was verified to involve in regulating LINC00221-mediated ALL cell proliferation and apoptosis. In conclusion, LINC00221 suppressed ALL cell proliferation and boosted ALL cell apoptosis via sponging miR-152-3p to up-regulate ATP2A2.
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Liu Z, Yang S, Chen X, Dong S, Zhou S, Xu S. LncRNA LINC00467 acted as an oncogene in esophageal squamous cell carcinoma by accelerating cell proliferation and preventing cell apoptosis via the miR-485-5p/DPAGT1 axis. J Gastroenterol Hepatol 2021; 36:721-730. [PMID: 32720371 DOI: 10.1111/jgh.15201] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 07/15/2020] [Accepted: 07/23/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Esophageal carcinoma has been regarded as one of the top 10 common malignancies globally. Esophageal squamous cell carcinoma (ESCC) is an important subtype of esophageal carcinoma with approximately 20% survival rate. Long noncoding RNAs were documented to regulate the occurrence or progression of several tumors. However, neither the biological role nor the molecular mechanism of LINC00467 has been explored. This research is aimed to investigating the regulatory mechanism of LINC00467 in ESCC. METHODS In this study, a series of experiments including reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8, luciferase reporter, western blot, and RNA immunoprecipitation were designed and conducted to explore the potential function and mechanism of LINC00467 in ESCC. RESULTS According to experimental results, we found out upregulated LINC00467 improved cell proliferation, but hindered cell apoptosis. In mechanism, miR-485-5p was predicted, screened out, and validated to combine with LINC00467, which displayed lower expression in ESCC. Additionally, miR-485-5p negatively regulated and directly targeted DPAGT1. Rescue assays suggested that DPAGT1 amplification was able to recover the influence of LINC00467 deficiency on cell proliferation and apoptosis. Furthermore, knockdown of LINC00467 suppressed tumor growth in vivo. CONCLUSION We proved that LINC00467 acted as an oncogene in ESCC by accelerating cell proliferation and preventing cell apoptosis via miR-485-5p/DPAGT1 axis. This may provide a potential diagnostic marker for ESCC treatment.
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Affiliation(s)
- Zhenghua Liu
- Department of Thoracic Surgery, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Shize Yang
- Department of Thoracic Surgery, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xitao Chen
- Department of Thoracic Surgery, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Siyuan Dong
- Department of Thoracic Surgery, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Siyu Zhou
- Department of Thoracic Surgery, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Shun Xu
- Department of Thoracic Surgery, First Affiliated Hospital of China Medical University, Shenyang, China
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LncRNA PVT1 promotes the malignant progression of acute myeloid leukaemia via sponging miR-29 family to increase WAVE1 expression. Pathology 2021; 53:613-622. [PMID: 33558065 DOI: 10.1016/j.pathol.2020.11.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 11/03/2020] [Accepted: 11/08/2020] [Indexed: 11/23/2022]
Abstract
LncRNA PVT1 has been demonstrated to be upregulated in acute myeloid leukaemia (AML) patients and indicates a poor prognosis. Nevertheless, its role in AML remains obscure. This study investigated the regulatory role and potential mechanisms of PVT1 in the progression of AML. Expression of PVT1, miR-29 family and WAVE1 was detected by quantitative real-time polymerase chain reaction. CCK8 and EdU assays were performed to assess the proliferation of AML cells. Cell cycle and apoptosis were determined by propidium iodide (PI) staining and Annexin V/PI staining on a flow cytometer. Transwell assay was carried out to evaluate the migration and invasion abilities. The interaction between miR-29 family and PVT1/WAVE1 was confirmed by dual luciferase reporter assay and RNA immunoprecipitation assay. The protein levels of WAVE1, Bcl-2, Bax, cleaved Caspase 3, cyclin D1, and p21 were detected by western blotting. Xenograft transplantation was performed to determine the tumourigenicity of AML cell in vivo. PVT1 expression was significantly increased in AML patient samples and cells, which positively correlated with WAVE1 expression. Silencing of PVT1 restrained growth, migration and invasion, while inducing apoptosis of AML cells. Moreover, PVT1 acted as a sponge for miR-29 family to increase WAVE1 expression in AML cells. Overexpression of WAVE1 partly counteracted PVT1 knockdown-induced anti-tumour effects on AML cells in vitro and xenograft tumour in vivo. PVT1 facilitated the progression of AML via regulating miR-29 family/WAVE1 axis, which supported the conclusion that PVT1 may be a promising therapeutic target for AML.
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Li L, Wan D, Li L, Qin Y, Ma W. lncRNA RAET1K Promotes the Progression of Acute Myeloid Leukemia by Targeting miR-503-5p/INPP4B Axis. Onco Targets Ther 2021; 14:531-544. [PMID: 33500628 PMCID: PMC7823139 DOI: 10.2147/ott.s291123] [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: 11/09/2020] [Accepted: 11/27/2020] [Indexed: 11/30/2022] Open
Abstract
Background Although long non-coding RNA (lncRNA) RAET1K has been observed to be abnormally expressed in patients with various cancers, its role and molecular mechanism in acute myeloid leukemia (AML) remain unclear. Methods The expression of RAET1K and miR-503-5p in bone marrow tissues and cell lines was detected by qRT-PCR. Cell proliferation was evaluated by cell counting kit-8 and 5-ethynyl-20-deoxyuridine (EdU) staining assay. Cell invasion and migration were detected by transwell assay. Cell apoptosis was evaluated by flow cytometry. The relationship between RAET1K and miR-503-5p, as well as miR-503-5p and INPP4B, was determined by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In addition, the tumorigenesis of leukemia cells was evaluated by using a xenograft mouse model in vivo. Results RAET1K was significantly upregulated and miR-503-5p was markedly downregulated in bone marrow tissues and cell lines (HL-60 and THP-1). Silencing of RAET1K (si-RAET1K) and overexpression of miR-503-5p inhibited cell proliferation, migration, and invasion but promoted apoptosis of HL-60 and THP-1 cells. RAET1K functioned as a sponge of miR-503-5p, and miR-503-5p inhibitor obviously attenuated the effect of si-RAET1K on AML progression in vitro. INPP4B was identified as a target of miR-503-5p, and INPP4B overexpression obviously reversed the effect of miR-503-5p mimics on cell proliferation, migration, invasion, and apoptosis of HL-60 and THP-1 cells in vitro. Knockdown of RAET1K effectively inhibited the tumorigenesis of leukemia cells in vivo. Conclusion Our results demonstrated that RAET1K/miR-503-5p/INPP4B axis contributed to AML progression, suggesting that RAET1K might be a potential target for the treatment of AML.
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Affiliation(s)
- Li Li
- Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People's Republic of China
| | - Dingming Wan
- Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People's Republic of China
| | - Lin Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People's Republic of China
| | - Yang Qin
- Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People's Republic of China
| | - Wang Ma
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450052, People's Republic of China
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Su H, Wang M, Pang X, Guan F, Li X, Cheng Y. When Glycosylation Meets Blood Cells: A Glance of the Aberrant Glycosylation in Hematological Malignancies. Rev Physiol Biochem Pharmacol 2021; 180:85-117. [PMID: 34031738 DOI: 10.1007/112_2021_60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of hematological malignancy progression. Alterations in glycosylation appear to not only directly impact cell growth and survival, but also alter the adhesion of tumor cells and their interactions with the microenvironment, facilitating cancer-induced immunomodulation and eventual metastasis. Changes in glycosylation arise from altered expression of glycosyltransferases, enzymes that catalyze the transfer of saccharide moieties to a wide range of acceptor substrates, such as proteins, lipids, and other saccharides in the endoplasmic reticulum (ER) and Golgi apparatus. Novel glycan structures in hematological malignancies represent new targets for the diagnosis and treatment of blood diseases. This review summarizes studies of the aberrant expression of glycans commonly found in hematological malignancies and their potential mechanisms and defines the specific roles of glycans as drivers or passengers in the development of hematological malignancies.
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Affiliation(s)
- Huining Su
- Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Mimi Wang
- Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Xingchen Pang
- Key Laboratory of Resource Biology and Biotechnology Western China, College of Life Science, Northwest University, Xi'an, China
| | - Feng Guan
- Key Laboratory of Resource Biology and Biotechnology Western China, College of Life Science, Northwest University, Xi'an, China
| | - Xiang Li
- Key Laboratory of Resource Biology and Biotechnology Western China, College of Life Science, Northwest University, Xi'an, China.
| | - Ying Cheng
- Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
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Zhang X, Yang L, Xu G. Silencing of long noncoding RNA TUG1 inhibits viability and promotes apoptosis of acute myeloid leukemia cells by targeting microRNA-221-3p/KIT axis. Clin Hemorheol Microcirc 2020; 76:425-437. [PMID: 32804119 DOI: 10.3233/ch-200906] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE: Acute myeloid leukemia (AML) is a hematological malignancy. This study was attempted to uncover the effects of long noncoding RNA taurine-upregulated gene1 (TUG1) on the viability and apoptosis of AML cells. METHODS: QRT-PCR was implemented to examine the expression of TUG1, miR-221-3p and KIT in AML. The correlation between TUG1 and clinicopathological features of AML patients was evaluated. The effect of TUG1 on AML cells were studied by RNA interference approach. AML cells were transfected with miR-221-3p mimic and miR-221-3p inhibitor, respectively. Then the viability and apoptosis of AML cells were examined by MTT and flow cytometry assay, respectively. Additionally, dual-luciferase reporter assay was used to confirm the interactions among TUG1, miR-221-3p and KIT. Western blot was applied to analyze protein expression of KIT. RESULTS: The expression of TUG1 and KIT was up-regulated in AML, but miR-221-3p was down-regulated. TUG1 expression had obviously correlation with World Health Organization (WHO) grade in AML patients. The functional experiment stated that TUG1 silencing suppressed the viability and accelerated the apoptosis of AML cells. Moreover, the mechanical experiment demonstrated that TUG1 and KIT were both targeted by miR-221-3p with the complementary binding sites at 3’UTR. Up-regulation of miR-221-3p inhibited the protein expression of KIT. Furthermore, in the feedback experiment, miR-221-3p inhibition or KIT overexpression reversed the repression of tumor behavior induced by TUG1 silencing. CONCLUSIONS: TUG1 silencing retarded viability and promoted apoptosis of AML cells via regulating miR-221-3p/KIT axis, providing a potential therapeutic target for AML.
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Affiliation(s)
- Xifeng Zhang
- Pediatric Intensive Care Unit, Liaocheng Second People’s Hospital, Affiliated to the First Medical University of Shandong, Linqing, China
| | - Likun Yang
- Pediatric Intensive Care Unit, Liaocheng Second People’s Hospital, Affiliated to the First Medical University of Shandong, Linqing, China
| | - Guixia Xu
- Pediatric Intensive Care Unit, Liaocheng Second People’s Hospital, Affiliated to the First Medical University of Shandong, Linqing, China
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Xiao Y, Ming X, Wu J. Hsa_circ_0002483 regulates miR-758-3p/MYC axis to promote acute myeloid leukemia progression. Hematol Oncol 2020; 39:243-253. [PMID: 33283885 DOI: 10.1002/hon.2829] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 11/10/2020] [Accepted: 12/02/2020] [Indexed: 12/21/2022]
Abstract
Circular RNAs are relevant to progression of acute myeloid leukemia (AML). Nevertheless, how and whether hsa_circ_0002483 (circ_0002483) participates in AML progression are largely uncertain. The bone marrow samples were harvested from 31 AML patients or 31 normal subjects. Circ_0002483, microRNA (miR)-758-3p and myelocytomatosis oncogene (MYC) abundances were examined via quantitative reverse transcription polymerase chain reaction and Western blot. Cell proliferation, cycle process and apoptosis were analyzed via Cell Counting Kit-8, flow cytometry, caspase 3 activity and related protein levels. Target relationship was investigated by dual-luciferase reporter assay and RNA immunoprecipitation. Circ_0002483 expression was elevated in AML patients and cells. Circ_0002483 silence constrained AML cell proliferation and facilitated cell cycle arrest and apoptosis. miR-758-3p was reduced in AML and decreased via circ_0002483. miR-758-3p down-regulation mitigated the inhibitive influence of circ_0002483 interference on AML progression. MYC was decreased by miR-758-3p, and circ_0002483 could regulate MYC expression by miR-758-3p. miR-758-3p overexpression restrained cell proliferation and promoted cycle arrest and apoptosis via decreasing MYC. Circ_0002483 knockdown repressed AML cell proliferation and promoted cycle arrest and apoptosis via controlling miR-758-3p/MYC axis.
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Affiliation(s)
- Yi Xiao
- Department of Hematology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China
| | - Xi Ming
- Department of Hematology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China
| | - Jiaying Wu
- Department of Hematology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China
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Xu B, Mei J, Ji W, Bian Z, Jiao J, Sun J, Shao J. LncRNA SNHG3, a potential oncogene in human cancers. Cancer Cell Int 2020; 20:536. [PMID: 33292213 PMCID: PMC7640707 DOI: 10.1186/s12935-020-01608-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/15/2020] [Indexed: 02/06/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) are composed of > 200 nucleotides; they lack the ability to encode proteins but play important roles in a variety of human tumors. A large number of studies have shown that dysregulated expression of lncRNAs is related to tumor oncogenesis and progression. Emerging evidence shows that SNHG3 is a novel oncogenic lncRNA that is abnormally expressed in various tumors, including osteosarcoma, liver cancer, lung cancer, etc. SNHG3 primarily competes as a competitive endogenous RNA (ceRNA) that targets tumor suppressor microRNAs (miRNAs) and ceRNA mechanisms that regulate biological processes of tumors. In addition, abnormal expression of SNHG3 is significantly correlated with patient clinical features. Upregulation of SNHG3 contributes to biological functions, including tumor cell proliferation, migration, invasion and EMT. Therefore, SNHG3 may represent a potential diagnostic and prognostic biomarker, as well as a novel therapeutic target.
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Affiliation(s)
- Bin Xu
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Jie Mei
- Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China
| | - Wei Ji
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Zheng Bian
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Jiantong Jiao
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China
| | - Jun Sun
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China.
| | - Junfei Shao
- Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qing Yang Road, Wuxi, 214023, Jiangsu, China.
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Shi J, Ding W, Lu H. Identification of Long Non-Coding RNA SNHG Family as Promising Prognostic Biomarkers in Acute Myeloid Leukemia. Onco Targets Ther 2020; 13:8441-8450. [PMID: 32922034 PMCID: PMC7457734 DOI: 10.2147/ott.s265853] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 08/03/2020] [Indexed: 12/13/2022] Open
Abstract
Background Small nucleolar RNA host gene (SNHG) family members are newly recognized lncRNAs, which have been revealed to be oncogenes in several cancers. However, little studies investigated the expression and clinical implications of SNHGs in AML. Methods Herein, we systemically determined the prognostic role of the expression of SNHG family members in acute myeloid leukemia (AML). Results Among the expression of all SNHG family members, we identified that only SNHG7 and SNHG12 expression were found to have prognostic effects on overall survival (OS) and leukemia-free survival (LFS) in AML by Cox regression univariate analysis. Furthermore, Kaplan-Meier analysis showed that SNHG7 higher-expressed cases had markedly longer OS and LFS time than SNHG7 lower-expressed cases, whereas SNHG12 higher-expressed cases had markedly shorter OS and LFS time than SNHG12 lower-expressed cases. Interestingly, SNHG7 and SNHG12 expression were also associated with several prognosis-related clinical/molecular features such as white blood cell counts, FAB/cytogenetic classifications, IDH1 mutation, RUNX1 mutation, and NPM1 mutation. Despite the associations, Cox regression multivariate analysis confirmed the independent prognostic impact of SNHG7 and SNHG12 expression in AML. Notably, we further validated that both SNHG7 and SNHG12 expression was significantly increased in newly diagnosed AML patients. Conclusion Our findings demonstrated that SNHG7 and SNHG12 expression act as independent prognostic indicators in AML.
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Affiliation(s)
- Jian Shi
- Enzymology Laboratory, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People's Republic of China
| | - Weifeng Ding
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People's Republic of China
| | - Hong Lu
- Eye Institute, Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People's Republic of China
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Li J, Wang M, Chen X. Long non-coding RNA UCA1 modulates cell proliferation and apoptosis by regulating miR-296-3p/Myc axis in acute myeloid leukemia. Cell Cycle 2020; 19:1454-1465. [PMID: 32286143 DOI: 10.1080/15384101.2020.1750814] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Acute myeloid leukemia (AML) is a common hematopoietic malignancy with a generally poor prognosis. Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogene in various malignancies including AML. However, the role and mechanisms of UCA1 in AML tumorigenesis were incompletely understood. Hence, this study aims to investigate whether UCA1 regulates AML progression by miR-296-3p/Myc axis. Cell proliferation and apoptosis were evaluated by MTT assay and flow cytometry, respectively. Luciferase reporter assay was performed to analyze the interaction between miR-296-3p and UCA1 or Myc. The results showed that UCA1 knockdown inhibited proliferation and induced apoptosis in AML cells (U937 and HL60). Mechanistically, UCA1 acted as a sponge of miR-296-3p by binding to miR-296-3p. Myc, a target of miR-296-3p, was positively regulated by UCA1. Functional assay showed that the anti-AML effect of UCA1 knockdown could be abrogated by miR-296-3p inhibition and Myc overexpression. Moreover, UCA1 knockdown inhibited AML cell tumorigenesis in vivo, which was associated with regulation of miR-296-3p and Myc expression. In conclusion, UCA1 modulates AML progression by regulating miR-296-3p/Myc axis.
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Affiliation(s)
- Jiajia Li
- Department of Hematology, The First Affiliated Hospital of Bengbu Medical College , Bengbu, Anhui, PR China
| | - Meng Wang
- Department of Hematology, The First Affiliated Hospital of Bengbu Medical College , Bengbu, Anhui, PR China
| | - Xiaofeng Chen
- Department of Hematology, The First Affiliated Hospital of Bengbu Medical College , Bengbu, Anhui, PR China
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Feng S, Liu N, Chen X, Liu Y, An J. Long non-coding RNA NEAT1/miR-338-3p axis impedes the progression of acute myeloid leukemia via regulating CREBRF. Cancer Cell Int 2020; 20:112. [PMID: 32280304 PMCID: PMC7137299 DOI: 10.1186/s12935-020-01182-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 03/23/2020] [Indexed: 02/07/2023] Open
Abstract
Background Acute myeloid leukemia (AML) is a heterogeneous hematological disease. Our purpose of the research was to investigate the regulatory influence of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1)/microRNA-338-3p (miR-338-3p)/CREB3 regulatory factor (CREBRF) in AML progression. Methods The associated RNA and protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell growth was assessed through colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometry was exploited to determine the apoptosis rate. Cell migration and invasion were detected by transwell assay. The combination of miR-338-3p and NEAT1 or CREBRF was analyzed via the dual-luciferase reporter assay. Results NEAT1 and CREBRF were down-regulated in AML tissues and cells. NEAT1 up-regulation suppressed cell growth, migration and invasion but enhanced apoptosis of AML cells. Inhibition of CREBRF reverted the NEAT1-induced effects on AML cells. Moreover, NEAT1 directly targeted miR-338-3p and miR-338-3p targeted CREBRF. NEAT1/miR-338-3p could affect cellular behaviors of AML cells via the modulation of CREBRF. Conclusion NEAT1/miR-338-3p axis repressed the AML progression through regulating CREBRF, which might afford a favorable perspective for the AML treatment molecularly.
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Affiliation(s)
- Song Feng
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Na Liu
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Xiaoguang Chen
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Yufeng Liu
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Jindou An
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
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Bhat AA, Younes SN, Raza SS, Zarif L, Nisar S, Ahmed I, Mir R, Kumar S, Sharawat SK, Hashem S, Elfaki I, Kulinski M, Kuttikrishnan S, Prabhu KS, Khan AQ, Yadav SK, El-Rifai W, Zargar MA, Zayed H, Haris M, Uddin S. Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance. Mol Cancer 2020; 19:57. [PMID: 32164715 PMCID: PMC7069174 DOI: 10.1186/s12943-020-01175-9] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 03/02/2020] [Indexed: 12/12/2022] Open
Abstract
Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.
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Affiliation(s)
- Ajaz A Bhat
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Salma N Younes
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | - Lubna Zarif
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Sabah Nisar
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Ikhlak Ahmed
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Rashid Mir
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Sachin Kumar
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Surender K Sharawat
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Sheema Hashem
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Imadeldin Elfaki
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Michal Kulinski
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Shilpa Kuttikrishnan
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Kirti S Prabhu
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Abdul Q Khan
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | - Santosh K Yadav
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar
| | - Wael El-Rifai
- Department of Surgery, University of Miami, Miami, Florida, USA
| | - Mohammad A Zargar
- Department of Biotechnology, Central University of Kashmir, Ganderbal, Jammu and Kashmir, India
| | - Hatem Zayed
- Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar
| | - Mohammad Haris
- Translational Medicine, Sidra Medicine, P.O. Box 26999, Doha, Qatar.
- Laboratory Animal Research Center, Qatar University, Doha, Qatar.
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
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