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Ming J, Cheng F, Fu Y, Zhang M, Rou Q, Liu K, Nuertai Z, Xu S, Tao L, Abudujapar A, Liu Y. Long non-coding RNA H19 promotes cervical cancer development via targeting the microRNA-140/ALDH1A1 axis. Eur J Med Res 2025; 30:95. [PMID: 39940029 PMCID: PMC11823256 DOI: 10.1186/s40001-025-02350-8] [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: 11/07/2024] [Accepted: 01/31/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Dysregulation of long non-coding RNA H19 (lncRNA H19) is involved in cervical cancer (CC) progression. This study aims to unveil the specific role and relevant mechanism of lncRNA H19 in CC. METHODS The expression of lncRNA H19 in CC cells was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). CC cells were transfected with sh-H19, followed by cell proliferation, apoptosis, migration and invasion were examined. After location of H19 in cells using fluorescence in Situ Hybridization (FISH), target microRNAs (miRNAs) and genes associated with lncRNA H19 were predicted using bioinformatics analysis and validated by dual-luciferase reporter assay. Finally, the specific role of lncRNA H19 in CC was explored in vivo. RESULTS The upregulation of lncRNA H19 was observed in CC cells. LncRNA H19 knockdown inhibited the proliferation, migration, and invasion of CC cells, and remarkably promoted CC cell apoptosis. LncRNA H19 was localized in the nucleus and interacted with miR-140 that was downregulated in CC cells. MiR-140 inhibition reversed the effects of lncRNA H19 knockdown on CC cell development. MiR-140 targets ALDH1A1, and lncRNA H19 knockdown decreased the ALDH1A1 expression, which was rescued by miR-140 inhibition. In vivo experiments also shown that reduction of lncRNA H19 diminishes tumor growth via targeting the miR-140/ALDH1A1 axis. CONCLUSION LncRNA H19 promotes the malignant progression of CC through targeting miR-140/ALDH1A1 axis.
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Affiliation(s)
- Jie Ming
- Medical Imaging Center, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Fang Cheng
- Department of Special Needs Comprehensive, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Yating Fu
- Department of Radiology, Urumqi Stomatological Hospital, Urumqi, 830002, Xinjiang, China
| | - Meng Zhang
- Department of Special Needs Comprehensive, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Qian Rou
- Department of Special Needs Comprehensive, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Kaixiong Liu
- Department of Oncology, Bachu County People's Hospital, Bachu, 843800, Xinjiang, China
| | - Zinati Nuertai
- Department of Special Needs Comprehensive, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Shanshan Xu
- Department of Special Needs Comprehensive, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Ling Tao
- Department of Gynecology, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Alfira Abudujapar
- Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
| | - Ying Liu
- Department of Special Needs Comprehensive, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
- Department of Oncology, Bachu County People's Hospital, Bachu, 843800, Xinjiang, China.
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Yu YQ, Li SQ, Weng J, Li B, Qin LL, Lv J. LncRNA H19 Activates the RAS-MAPK Signaling Pathway via miR-140-5p/SOS1 Axis in Malignant Liver Tumors. Curr Med Sci 2024; 44:1232-1240. [PMID: 39565504 DOI: 10.1007/s11596-024-2949-0] [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: 07/15/2024] [Accepted: 09/12/2024] [Indexed: 11/21/2024]
Abstract
OBJECTIVE To study the influences of LncRNA H19 (H19) on malignant liver tumor cells and elucidate the underlying molecular mechanisms. METHODS H19 expression in liver tumor tissues, matched normal liver tissues, human liver malignant tumor cell lines and the human hepatocyte line LO2 was assessed via quantitative RT-PCR. Cell viability analysis and Matrigel invasion analysis were performed to evaluate the effects of H19 on cell proliferation and invasion. Luciferase reporter analysis was carried out to assess the interaction between miR-140-5p and SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1). The influence of H19 on the Ras-MAPK signalling pathway was evaluated by detecting key protein levels via active Ras pull-down analysis and Western blot analysis. RESULTS H19 expression was lower in liver cancer samples than in matched normal liver tissue samples. H19 overexpression enhanced the proliferation and invasion of HepG2 and SMMC-7721 cells. H19 overexpression increased the level of activated Ras. The expression levels of phosphorylated Raf, phosphorylated ERK and phosphorylated MEK were increased by H19 overexpression. H19 knockdown had the opposite effect. Treatment with a MAPK inhibitor significantly reversed the influence of H19 overexpression on liver malignant tumor cell growth and invasion. The MAPK activator reversed the opposing effects of H19 silencing. H19 overexpression increased the protein level of SOS1, and miR-140-5p directly targeted SOS1. CONCLUSION H19 can activate the Ras-MAPK signalling pathway via the miR-140-5p/SOS1 axis in malignant liver tumour cells.
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Affiliation(s)
- Ya-Qun Yu
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, Guilin, 541001, China
| | - Shu-Qun Li
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, Guilin, 541001, China
| | - Jun Weng
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, Guilin, 541001, China
| | - Bo Li
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, Guilin, 541001, China
| | - Li-Ling Qin
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical College, Guilin, 541001, China
| | - Jun Lv
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
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Doghish AS, Abd-Elmawla MA, Hatawsh A, Zaki MB, Aborehab NM, Radwan AF, Moussa R, Eisa MA, Mageed SSA, Mohammed OA, Abdel-Reheim MA, Elimam H. Unraveling the role of LncRNAs in glioblastoma progression: insights into signaling pathways and therapeutic potential. Metab Brain Dis 2024; 40:42. [PMID: 39589598 DOI: 10.1007/s11011-024-01456-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 09/27/2024] [Indexed: 11/27/2024]
Abstract
Glioblastoma (GBM) is one of the most aggressive types of brain cancer, characterized by its poor prognosis and low survival rate despite current treatment modalities. Because GBM is lethal, clarifying the pathogenesis's underlying mechanisms is important, which are still poorly understood. Recent discoveries in the fields of molecular genetics and cancer biology have demonstrated the critical role that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), play in the molecular pathophysiology of GBM growth. LncRNAs are transcripts longer than 200 nucleotides that do not encode proteins. They are significant epigenetic modulators that control gene e expression at several levels. Their dysregulation and interactions with important signaling pathways play a major role in the malignancy and development of GBM. The increasing role of lncRNAs in GBM pathogenesis is thoroughly examined in this review, with particular attention given to their regulation mechanisms in key signaling pathways such as PI3K/AKT, Wnt/β-catenin, and p53. It also looks into lncRNAs' potential as new biomarkers and treatment targets for GBM. In addition, the study discusses the difficulties in delivering lncRNA-based medicines across the blood-brain barrier and identifies areas that need more research to advance lncRNA-oriented treatments for this deadly cancer.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo, Badr City, 11829, Cairo, Egypt.
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt.
| | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Abdulrahman Hatawsh
- Biotechnology School, 26th of July Corridor, Nile University, Sheikh Zayed City, 12588, Giza, Egypt
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt
| | - Nora M Aborehab
- Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt
| | - Abdullah F Radwan
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, 11829, Egypt
| | - Rewan Moussa
- Faculty of Medicine, Helwan University, Cairo, 11795, Egypt
| | - Mahmoud A Eisa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11651, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo, Badr City, Cairo, 11829, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia
| | | | - Hanan Elimam
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt
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Leili FR, Shali N, Sheibani M, Jafarian MJ, Pashizeh F, Gerami R, Iraj F, Lashkarshekan AA. Detailed pathological role of non-coding RNAs (ncRNAs) in regulating drug resistance of glioblastoma, and update. Pathol Res Pract 2024; 263:155590. [PMID: 39326365 DOI: 10.1016/j.prp.2024.155590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 09/04/2024] [Accepted: 09/06/2024] [Indexed: 09/28/2024]
Abstract
Glioma is a kind of brain tumor that develops in the central nervous system and is classified based on its histology and molecular genetic features. The lifespan of patients does not exceed 22 months. One of the motives for the low effectiveness of glioma treatment is its radioresistance and chemoresistance. Noncoding RNAs (ncRNAs) are a diverse set of transcripts that do not undergo translation to become proteins in glioma. The ncRNAs have been identified as significant regulators of several biological processes in different cell types and tissues, and their abnormal function has been linked to glioma. They are known to impact important occurrences, including carcinogenesis, progression, and enhanced treatment resistance in glioma cells. The ncRNAs control cell proliferation, migration, epithelial-to-mesenchymal transition (EMT), invasion, and drug resistance in glioma cells. The main focus of this study is to inspect the involvement of ncRNAs in the drug resistance of glioma.
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Affiliation(s)
- Foad Rahmanpour Leili
- Department of Neurology Faculty of Medicine, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - Niloofar Shali
- Department of Clinical Biochemistry, School of Medicine, Shahrood Branch, Islamic Azad University, Shahrood, Iran
| | - Mehrnaz Sheibani
- Division of Pediatric Neurology, University of Tabriz, Tabriz, Iran
| | | | - Fatemeh Pashizeh
- Department of Immunology, School of Medicine, Shahid Sadoughi University of Medical Science, Yazd 8916188635, Iran
| | - Reza Gerami
- Department of Radiology, Faculty of Medicine, AJA University of Medical Science, Tehran, Iran.
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Darmadi D, Chugaeva UY, Saleh RO, Hjazi A, Saleem HM, Ghildiyal P, Alwaily ER, Alawadi A, Alnajar MJ, Ihsan A. Critical roles of long noncoding RNA H19 in cancer. Cell Biochem Funct 2024; 42:e4018. [PMID: 38644608 DOI: 10.1002/cbf.4018] [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: 01/06/2024] [Revised: 03/18/2024] [Accepted: 04/06/2024] [Indexed: 04/23/2024]
Abstract
Long noncoding RNAs (lncRNAs) are a category of noncoding RNAs characterized by their length, often exceeding 200 nucleotides. There is a growing body of data that indicate the significant involvement of lncRNAs in a wide range of disorders, including cancer. lncRNA H19 was among the initial lncRNAs to be identified and is transcribed from the H19 gene. The H19 lncRNA exhibits significant upregulation in a diverse range of human malignancies, such as breast, colorectal, pancreatic, glioma, and gastric cancer. Moreover, the overexpression of H19 is frequently associated with a worse prognosis among individuals diagnosed with cancer. H19 has been shown to have a role in facilitating several cellular processes, including cell proliferation, invasion, migration, epithelial-mesenchymal transition, metastasis, and apoptosis. This article summarizes the aberrant upregulation of H19 in human malignancies, indicating promising avenues for future investigations on cancer diagnostics and therapeutic interventions.
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Affiliation(s)
- Darmadi Darmadi
- Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, North Sumatera, Indonesia
| | - Uliana Y Chugaeva
- Department of Pediatric, Preventive Dentistry and Orthodontics, Institute of Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Raed Obaid Saleh
- Department of Medical Laboratory Techniques, Al-Maarif University College, Al-Anbar, Iraq
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Hiba Muwafaq Saleem
- Department of Biology, College of Science, University of Anbar, Ramadi, Iraq
| | - Pallavi Ghildiyal
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Enas R Alwaily
- Microbiology Research Group, College of Pharmacy, Al-Ayen University, Thi-Qar, Iraq
| | - Ahmed Alawadi
- College of Technical Engineering, The Islamic University, Najaf, Iraq
- College of Technical Engineering, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- College of Technical Engineering, The Islamic University of Babylon, Hillah, Iraq
| | | | - Ali Ihsan
- College of Technical Engineering, Imam Ja'afar Al-Sadiq University, Al-Muthanna, Iraq
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Shah M, Sarkar D. HCC-Related lncRNAs: Roles and Mechanisms. Int J Mol Sci 2024; 25:597. [PMID: 38203767 PMCID: PMC10779127 DOI: 10.3390/ijms25010597] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/21/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
Hepatocellular carcinoma (HCC) presents a significant global health threat, particularly in regions endemic to hepatitis B and C viruses, and because of the ongoing pandemic of obesity causing metabolic-dysfunction-related fatty liver disease (MAFLD), a precursor to HCC. The molecular intricacies of HCC, genetic and epigenetic alterations, and dysregulated signaling pathways facilitate personalized treatment strategies based on molecular profiling. Epigenetic regulation, encompassing DNA methyltion, histone modifications, and noncoding RNAs, functions as a critical layer influencing HCC development. Long noncoding RNAs (lncRNAs) are spotlighted for their diverse roles in gene regulation and their potential as diagnostic and therapeutic tools in cancer. In this review, we explore the pivotal role of lncRNAs in HCC, including MAFLD and viral hepatitis, the most prevalent risk factors for hepatocarcinogenesis. The dysregulation of lncRNAs is implicated in HCC progression by modulating chromatin regulation and transcription, sponging miRNAs, and influencing structural functions. The ongoing studies on lncRNAs contribute to a deeper comprehension of HCC pathogenesis and offer promising routes for precision medicine, highlighting the utility of lncRNAs as early biomarkers, prognostic indicators, and therapeutic targets.
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Affiliation(s)
- Mimansha Shah
- Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA;
| | - Devanand Sarkar
- Department of Human and Molecular Genetics, Massey Comprehensive Cancer Center, and VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA 23298, USA
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Zhang R, Zeng Y, Deng JL. Long non-coding RNA H19: a potential biomarker and therapeutic target in human malignant tumors. Clin Exp Med 2023; 23:1425-1440. [PMID: 36484927 DOI: 10.1007/s10238-022-00947-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/08/2022] [Indexed: 12/13/2022]
Abstract
Long non-coding RNAs play important roles in cellular functions and disease development. H19, as a long non-coding RNA, is pervasively over-expressed in almost all kinds of human malignant tumors. Although many studies have reported that H19 is closely associated with tumor cell proliferation, apoptosis, invasion, metastasis, and chemoresistance, the role and mechanism of H19 in gene regulation and tumor development are largely unclear. In this review, we summarized the recent progress in the study of the major functions and mechanisms of H19 lncRNA in cancer development and progression. H19 possesses both oncogenic and tumor-suppressing activities, presumably through regulating target gene transcription, mRNA stability and splicing, and competitive inhibition of endogenous RNA degradation. Studies indicate that H19 may involve in cell proliferation and apoptosis, tumor initiation, migration, invasion, metastasis and chemoresistance and may serve as a potential biomarker for early diagnosis, prognosis, and novel molecular target for cancer therapy.
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Affiliation(s)
- Rui Zhang
- Department of Pharmacy, Anhui No.2 Provincial People's Hospital, Hefei, 230041, People's Republic of China
| | - Ying Zeng
- Department of Pharmacy, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410008, People's Republic of China
| | - Jun-Li Deng
- Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People's Republic of China.
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Kunze R, Fischer S, Marti HH, Preissner KT. Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration. J Biomed Sci 2023; 30:64. [PMID: 37550658 PMCID: PMC10405513 DOI: 10.1186/s12929-023-00954-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 07/22/2023] [Indexed: 08/09/2023] Open
Abstract
Neurological disorders such as stroke, multiple sclerosis, as well as the neurodegenerative diseases Parkinson's or Alzheimer's disease are accompanied or even powered by danger associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue. Besides protein-related DAMPs or "alarmins", numerous nucleic acid DAMPs exist in body fluids, such as cell-free nuclear and mitochondrial DNA as well as different species of extracellular RNA, collectively termed as self-extracellular nucleic acids (SENAs). Among these, microRNA, long non-coding RNAs, circular RNAs and extracellular ribosomal RNA constitute the majority of RNA-based DAMPs. Upon tissue injury, necrosis or apoptosis, such SENAs are released from neuronal, immune and other cells predominantly in association with extracellular vesicles and may be translocated to target cells where they can induce intracellular regulatory pathways in gene transcription and translation. The majority of SENA-induced signaling reactions in the brain appear to be related to neuroinflammatory processes, often causally associated with the onset or progression of the respective disease. In this review, the impact of the diverse types of SENAs on neuroinflammatory and neurodegenerative diseases will be discussed. Based on the accumulating knowledge in this field, several specific antagonistic approaches are presented that could serve as therapeutic interventions to lower the pathological outcome of the indicated brain disorders.
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Affiliation(s)
- Reiner Kunze
- Institute of Physiology and Pathophysiology, Department of Cardiovascular Physiology, Ruprecht-Karls-University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany
| | - Silvia Fischer
- Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
| | - Hugo H. Marti
- Institute of Physiology and Pathophysiology, Department of Cardiovascular Physiology, Ruprecht-Karls-University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany
| | - Klaus T. Preissner
- Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
- Kerckhoff-Heart-Research-Institute, Department of Cardiology, Medical School, Justus-Liebig-University, Giessen, Germany
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Bhattacharjee R, Prabhakar N, Kumar L, Bhattacharjee A, Kar S, Malik S, Kumar D, Ruokolainen J, Negi A, Jha NK, Kesari KK. Crosstalk between long noncoding RNA and microRNA in Cancer. Cell Oncol (Dordr) 2023; 46:885-908. [PMID: 37245177 PMCID: PMC10356678 DOI: 10.1007/s13402-023-00806-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2023] [Indexed: 05/29/2023] Open
Abstract
miRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management.
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Affiliation(s)
- Rahul Bhattacharjee
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Neeraj Prabhakar
- Centre for Structural System Biology, Department of Physics, University of Hamburg, c/o DESY, Building 15, Notkestr. 852267, Hamburg, Germany
- Pharmacy, Abo Akademi University, Tykistökatu 6A, Turku, Finland
| | - Lamha Kumar
- School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, India
| | - Arkadyuti Bhattacharjee
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Sulagna Kar
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India
| | - Sumira Malik
- Amity Institute of Biotechnology, Amity University Jharkhand, Ranchi, Jharkhand, 834001, India
| | - Dhruv Kumar
- School of Health Sciences and Technology (SoHST), UPES University, Dehradun, Uttarakhand, India
| | - Janne Ruokolainen
- Department of Applied Physics, School of Science, Aalto University, Espoo, 00076, Finland
| | - Arvind Negi
- Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, 00076, Finland.
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering and Technology (SET), Sharda University, Greater Noida, 201310, UP, India.
- School of Bioengineering & Biosciences, Lovely Professional University, Phagwara, 144411, India.
- Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, 248007, India.
| | - Kavindra Kumar Kesari
- Department of Applied Physics, School of Science, Aalto University, Espoo, 00076, Finland.
- Faculty of Biological and Environmental Sciences, University of Helsinki, Biocentre 3, Helsinki, Finland.
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Kciuk M, Yahya EB, Mohamed MMI, Abdulsamad MA, Allaq AA, Gielecińska A, Kontek R. Insights into the Role of LncRNAs and miRNAs in Glioma Progression and Their Potential as Novel Therapeutic Targets. Cancers (Basel) 2023; 15:3298. [PMID: 37444408 DOI: 10.3390/cancers15133298] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/19/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Accumulating evidence supports that both long non-coding and micro RNAs (lncRNAs and miRNAs) are implicated in glioma tumorigenesis and progression. Poor outcome of gliomas has been linked to late-stage diagnosis and mostly ineffectiveness of conventional treatment due to low knowledge about the early stage of gliomas, which are not possible to observe with conventional diagnostic approaches. The past few years witnessed a revolutionary advance in biotechnology and neuroscience with the understanding of tumor-related molecules, including non-coding RNAs that are involved in the angiogenesis and progression of glioma cells and thus are used as prognostic biomarkers as well as novel therapeutic targets. The emerging research on lncRNAs and miRNAs highlights their crucial role in glioma progression, offering new insights into the disease. These non-coding RNAs hold significant potential as novel therapeutic targets, paving the way for innovative treatment approaches against glioma. This review encompasses a comprehensive discussion about the role of lncRNAs and miRNAs in gene regulation that is responsible for the promotion or the inhibition of glioma progression and collects the existing links between these key cancer-related molecules.
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Affiliation(s)
- Mateusz Kciuk
- Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland
- Doctoral School of Exact and Natural Sciences, University of Lodz, 90-237 Lodz, Poland
| | - Esam Bashir Yahya
- Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Penang 11800, Malaysia
| | | | - Muhanad A Abdulsamad
- Department of Molecular Biology, Faculty of Science, Sabratha University, Sabratha 00218, Libya
| | - Abdulmutalib A Allaq
- Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Malaysia
| | - Adrianna Gielecińska
- Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland
- Doctoral School of Exact and Natural Sciences, University of Lodz, 90-237 Lodz, Poland
| | - Renata Kontek
- Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland
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Taheri F, Ebrahimi SO, Heidari R, Pour SN, Reiisi S. Mechanism and function of miR-140 in human cancers: A review and in silico study. Pathol Res Pract 2023; 241:154265. [PMID: 36509008 DOI: 10.1016/j.prp.2022.154265] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/27/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022]
Abstract
MicroRNA-140 (miR-140) acts as a tumor suppressor and plays a vital role in cell biological functions such as cell proliferation, apoptosis, and DNA repair. The expression of this miRNA has been shown to be considerably decreased in cancer tissues and cell lines compared with normal adjacent tissues. Consequently, aberrant expression of some miR-140 target genes can lead to the initiation and progression of various human cancers, such as breast cancer, gastrointestinal cancers, lung cancer, and prostate cancer. The dysregulation of the miR-140 network also affects cell proliferation, invasion, metastasis, and apoptosis of cancer cells by affecting various signaling pathways. Besides, up-regulation of miR-140 could enhance the efficacy of chemotherapeutic agents in different cancer. We aimed to cover most aspects of miR-140 function in cancer development and address its importance in different stages of cancer progression.
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Affiliation(s)
- Forough Taheri
- Department of Genetics, Sharekord Branch, Islamic Azad University, Sharekord, Iran
| | - Seyed Omar Ebrahimi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | - Razieh Heidari
- Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Somaye Nezamabadi Pour
- Department of Obstetrics and Gynecology, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Somayeh Reiisi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran.
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12
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Hashemi M, Moosavi MS, Abed HM, Dehghani M, Aalipour M, Heydari EA, Behroozaghdam M, Entezari M, Salimimoghadam S, Gunduz ES, Taheriazam A, Mirzaei S, Samarghandian S. Long non-coding RNA (lncRNA) H19 in human cancer: From proliferation and metastasis to therapy. Pharmacol Res 2022; 184:106418. [PMID: 36038043 DOI: 10.1016/j.phrs.2022.106418] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/24/2022] [Accepted: 08/24/2022] [Indexed: 02/07/2023]
Abstract
Initiation and development of cancer depend on multiple factors that mutations in genes and epigenetic level can be considered as important drivers. Epigenetic factors include a large family of members and understanding their function in cancer has been a hot topic. LncRNAs are RNA molecules with no capacity in synthesis of proteins, and they have regulatory functions in cells. LncRNAs are localized in nucleus and cytoplasm, and their abnormal expression is related to development of tumor. This manuscript emphasizes on the role of lncRNA H19 in various cancers and its association with tumor hallmarks. The function of lncRNA H19 in most tumors is oncogenic and therefore, tumor cells increase its expression for promoting their progression. LncRNA H19 contributes to enhancing growth and cell cycle of cancers and by EMT induction, it is able to elevate metastasis rate. Silencing H19 induces apoptotic cell death and disrupts progression of tumors. LncRNA H19 triggers chemo- and radio-resistance in cancer cells. miRNAs are dually upregulated/down-regulated by lncRNA H19 in increasing tumor progression. Anti-cancer agents reduce lncRNA H19 in impairing tumor progression and increasing therapy sensitivity. A number of downstream targets and molecular pathways for lncRNA H19 have been detected in cancers including miRNAs, RUNX1, STAT3, β-catenin, Akt2 and FOXM1. Clinical studies have revealed potential of lncRNA H19 as biomarker and its association with poor prognosis. LncRNA H19 can be transferred to cancer cells via exosomes in enhancing their progression.
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Affiliation(s)
- Mehrdad Hashemi
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Marzieh Sadat Moosavi
- Department of Biochemistry, Faculty of Advanced Science and Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
| | - Hedyeh Maghareh Abed
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maryam Dehghani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Masoumeh Aalipour
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Elaheh Ali Heydari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mitra Behroozaghdam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Emine Selda Gunduz
- Vocational School of Health Services, Department of First and Emergency Aid, Akdeniz University, Antalya, Turkey.
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran.
| | - Saeed Samarghandian
- Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran.
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13
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Mousavi SM, Derakhshan M, Baharloii F, Dashti F, Mirazimi SMA, Mahjoubin-Tehran M, Hosseindoost S, Goleij P, Rahimian N, Hamblin MR, Mirzaei H. Non-coding RNAs and glioblastoma: Insight into their roles in metastasis. Mol Ther Oncolytics 2022; 24:262-287. [PMID: 35071748 PMCID: PMC8762369 DOI: 10.1016/j.omto.2021.12.015] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Glioma, also known as glioblastoma multiforme (GBM), is the most prevalent and most lethal primary brain tumor in adults. Gliomas are highly invasive tumors with the highest death rate among all primary brain malignancies. Metastasis occurs as the tumor cells spread from the site of origin to another site in the brain. Metastasis is a multifactorial process, which depends on alterations in metabolism, genetic mutations, and the cancer microenvironment. During recent years, the scientific study of non-coding RNAs (ncRNAs) has led to new insight into the molecular mechanisms involved in glioma. Many studies have reported that ncRNAs play major roles in many biological procedures connected with the development and progression of glioma. Long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are all types of ncRNAs, which are commonly dysregulated in GBM. Dysregulation of ncRNAs can facilitate the invasion and metastasis of glioma. The present review highlights some ncRNAs that have been associated with metastasis in GBM. miRNAs, circRNAs, and lncRNAs are discussed in detail with respect to their relevant signaling pathways involved in metastasis.
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Affiliation(s)
- Seyed Mojtaba Mousavi
- Department of Neurosciences and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Derakhshan
- Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatereh Baharloii
- Department of Cardiology, Chamran Cardiovascular Research Education Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Mohammad Ali Mirazimi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Mahjoubin-Tehran
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saereh Hosseindoost
- Brain and Spinal Cord Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Pouya Goleij
- Department of Genetics, Faculty of Biology, Sana Institute of Higher Education, Sari, Iran
| | - Neda Rahimian
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Department of Internal Medicine, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Michael R. Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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14
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Zhong X, Cai Y. Long non-coding RNA (lncRNA) HOXD-AS2 promotes glioblastoma cell proliferation, migration and invasion by regulating the miR-3681-5p/MALT1 signaling pathway. Bioengineered 2021; 12:9113-9127. [PMID: 34802389 PMCID: PMC8810070 DOI: 10.1080/21655979.2021.1977104] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 11/20/2022] Open
Abstract
Glioblastoma (GBM) is the most lethal type of brain cancer. An increasing number of studies suggest that long non-coding RNAs (lncRNAs) are implicated in tumor progression. LncRNA HOXD-AS2 was reported to be highly expressed in glioma and associated with glioma grade and poor prognosis. However, the molecular mechanism remains to be elucidated. In this study, we first analyzed differentially expressed lncRNAs in glioblastoma using RNA-seq dataset (156 GBM samples and 5 adjacent normal samples in TCGA (Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database). HOXD-AS2 was found to be significantly up-regulated in GBM tissues, which was further confirmed in GBM patient tumor samples and GBM cell lines. Silencing HOXD-AS2 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. We further identified and validated miR-3681-5p as a target of HOXD-AS2, and miR-3681-5p was negatively regulated by HOXD-AS2. By negatively affecting miR-3681-5p, HOXD-AS2 could promote the expression of MALT1 to augment the aggressiveness of GBM cells. miR-3681-5p overexpression or MALT1 knockdown attenuated aggressiveness of GBM cells. Importantly, silencing HOXD-AS2 suppressed tumorigenesis of GBM cells in the xenograft mouse model. Collectively, our study clarified the role of miR-3681-5p/MALT1 axis underlying the oncogenic function of lncRNA HOXD-AS2 in GBM. Future work is required to study the mechanism by which HOXD-AS2 is upregulated in GBM cells, which can provide novel insights into therapeutic intervention for GBM treatment.
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Affiliation(s)
- Xingming Zhong
- Department of Neurosurgery, The First People’s Hospital of Huzhou, the First Affiliated Hospital of Huzhou University, Huzhou, China
| | - Yong Cai
- Department of Neurosurgery, The First People’s Hospital of Huzhou, the First Affiliated Hospital of Huzhou University, Huzhou, China
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15
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Genomic instability in lower-grade glioma: Prediction of prognosis based on lncRNA and immune infiltration. MOLECULAR THERAPY-ONCOLYTICS 2021; 22:431-443. [PMID: 34553030 PMCID: PMC8430277 DOI: 10.1016/j.omto.2021.07.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 07/17/2021] [Indexed: 12/11/2022]
Abstract
Glioma is the most common type of primary malignant tumor in the central nervous system. Tumor recurrence and progression are common in lower-grade glioma (LGG). Immune checkpoint blockade (ICB), as an emerging immunotherapy, is expected to improve the prognosis of patients undergoing conventional treatment, but it currently performs poorly in glioma. We divided patients into genome-stable and -unstable groups according to the somatic mutation count and then found that the expression of CDC20 was positively correlated with genomic instability. We compared the differences in long non-coding RNA (lncRNA) expression and immune infiltration between the two groups. Five lncRNAs and three immune cell types were identified to construct risk models and a nomogram combing clinical features. Through internal and external validation, the models exhibited sufficient ability to predict the prognosis and the possible response to ICB therapy of patients. This study provided a potential predictive approach for the precise application of ICB and support for improving the prognosis of LGG patients.
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16
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Yang J, Qi M, Fei X, Wang X, Wang K. LncRNA H19: A novel oncogene in multiple cancers. Int J Biol Sci 2021; 17:3188-3208. [PMID: 34421359 PMCID: PMC8375239 DOI: 10.7150/ijbs.62573] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/14/2021] [Indexed: 12/13/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are a series of non-coding RNAs that lack open reading frameworks. Accumulating evidence suggests important roles for lncRNAs in various diseases, including cancers. Recently, lncRNA H19 (H19) became a research focus due to its ectopic expression in human malignant tumors, where it functioned as an oncogene. Subsequently, H19 was confirmed to be involved in tumorigenesis and malignant progression in many tumors and had been implicated in promoting cell growth, invasion, migration, epithelial-mesenchymal transition, metastasis, and apoptosis. H19 also sequesters some microRNAs, facilitating a multilayer molecular regulatory mechanism. In this review, we summarize the abnormal overexpression of H19 in human cancers, which suggests wide prospects for further research into the diagnosis and treatment of cancers.
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Affiliation(s)
- Jun Yang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Manlong Qi
- Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Xiang Fei
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Xia Wang
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Kefeng Wang
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, China
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17
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Singh N. Role of mammalian long non-coding RNAs in normal and neuro oncological disorders. Genomics 2021; 113:3250-3273. [PMID: 34302945 DOI: 10.1016/j.ygeno.2021.07.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 07/10/2021] [Accepted: 07/14/2021] [Indexed: 12/09/2022]
Abstract
Long non-coding RNAs (lncRNAs) are expressed at lower levels than protein-coding genes but have a crucial role in gene regulation. LncRNA is distinct, they are being transcribed using RNA polymerase II, and their functionality depends on subcellular localization. Depending on their niche, they specifically interact with DNA, RNA, and proteins and modify chromatin function, regulate transcription at various stages, forms nuclear condensation bodies and nucleolar organization. lncRNAs may also change the stability and translation of cytoplasmic mRNAs and hamper signaling pathways. Thus, lncRNAs affect the physio-pathological states and lead to the development of various disorders, immune responses, and cancer. To date, ~40% of lncRNAs have been reported in the nervous system (NS) and are involved in the early development/differentiation of the NS to synaptogenesis. LncRNA expression patterns in the most common adult and pediatric tumor suggest them as potential biomarkers and provide a rationale for targeting them pharmaceutically. Here, we discuss the mechanisms of lncRNA synthesis, localization, and functions in transcriptional, post-transcriptional, and other forms of gene regulation, methods of lncRNA identification, and their potential therapeutic applications in neuro oncological disorders as explained by molecular mechanisms in other malignant disorders.
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Affiliation(s)
- Neetu Singh
- Molecular Biology Unit, Department of Centre for Advance Research, King George's Medical University, Lucknow, Uttar Pradesh 226 003, India.
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18
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Momtazmanesh S, Rezaei N. Long Non-Coding RNAs in Diagnosis, Treatment, Prognosis, and Progression of Glioma: A State-of-the-Art Review. Front Oncol 2021; 11:712786. [PMID: 34322395 PMCID: PMC8311560 DOI: 10.3389/fonc.2021.712786] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 06/25/2021] [Indexed: 12/12/2022] Open
Abstract
Glioma is the most common malignant central nervous system tumor with significant mortality and morbidity. Despite considerable advances, the exact molecular pathways involved in tumor progression are not fully elucidated, and patients commonly face a poor prognosis. Long non-coding RNAs (lncRNAs) have recently drawn extra attention for their potential roles in different types of cancer as well as non-malignant diseases. More than 200 lncRNAs have been reported to be associated with glioma. We aimed to assess the roles of the most investigated lncRNAs in different stages of tumor progression and the mediating molecular pathways in addition to their clinical applications. lncRNAs are involved in different stages of tumor formation, invasion, and progression, including regulating the cell cycle, apoptosis, autophagy, epithelial-to-mesenchymal transition, tumor stemness, angiogenesis, the integrity of the blood-tumor-brain barrier, tumor metabolism, and immunological responses. The well-known oncogenic lncRNAs, which are upregulated in glioma, are H19, HOTAIR, PVT1, UCA1, XIST, CRNDE, FOXD2-AS1, ANRIL, HOXA11-AS, TP73-AS1, and DANCR. On the other hand, MEG3, GAS5, CCASC2, and TUSC7 are tumor suppressor lncRNAs, which are downregulated. While most studies reported oncogenic effects for MALAT1, TUG1, and NEAT1, there are some controversies regarding these lncRNAs. Expression levels of lncRNAs can be associated with tumor grade, survival, treatment response (chemotherapy drugs or radiotherapy), and overall prognosis. Moreover, circulatory levels of lncRNAs, such as MALAT1, H19, HOTAIR, NEAT1, TUG1, GAS5, LINK-A, and TUSC7, can provide non-invasive diagnostic and prognostic tools. Modulation of expression of lncRNAs using antisense oligonucleotides can lead to novel therapeutics. Notably, a profound understanding of the underlying molecular pathways involved in the function of lncRNAs is required to develop novel therapeutic targets. More investigations with large sample sizes and increased focus on in-vivo models are required to expand our understanding of the potential roles and application of lncRNAs in glioma.
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Affiliation(s)
- Sara Momtazmanesh
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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19
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Insights into how H19 works in glioma cells. A review article. Cancer Treat Res Commun 2021; 28:100411. [PMID: 34107413 DOI: 10.1016/j.ctarc.2021.100411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/25/2021] [Accepted: 05/26/2021] [Indexed: 11/22/2022]
Abstract
Glioblastoma is a highly aggressive brain tumor and considered to be the most common primary one. Recurrence after treatment is a significant problem, with a survival rate after one year of about 39.7%. The recurrence of GBM is linked to different cellular pathways and molecular signaling. Long non-coding RNA (LncRNA) comprises more than 200 nucleotides and is suggested to play a role in controlling genes that regulate the cell cycle, apoptosis and cellular growth in various tissues. Little is known about LncRNA compared to microRNAs, which are extensively studied in the literature. H19 is one of the most plentiful and conserved transcripts suggested to be involved in mammalian development and tumorigenesis. H19 is one of the LncRNA members transcribed by RNA polymerase II, spliced and polyadenylated, and the product is transferred to the cytoplasm without translation. HI9 maps to 1lp15, a region thought to be relevant to some childhood tumors as embryonal rhabdomyosarcoma and Wilm's Tumor. In these tumors, the analysis of the 11p15 locus showed loss of heterozygosity which is a feature associated with the tumor-suppressing activity. However, the role played by H19 in GBM is still enigmatic and needs further extensive evaluation. Uncovering the hidden role of such molecules in the pathogenesis in glioma will help tailor new targeted therapies that may affect the prognosis and survival of GBM.
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20
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Long non-coding RNA H19: Physiological functions and involvements in central nervous system disorders. Neurochem Int 2021; 148:105072. [PMID: 34058282 DOI: 10.1016/j.neuint.2021.105072] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 05/08/2021] [Accepted: 05/16/2021] [Indexed: 12/26/2022]
Abstract
Central nervous system (CNS) disorders are some of the most complex and challenging diseases because of the intricate structure and functions of the CNS. Long non-coding RNA (LncRNA) H19, which had been mistaken for "transcription noise" previously, has now been found to be closely related to the development and homeostasis of the CNS. Several recent studies indicate that it plays an important role in the pathogenesis, treatment, and even prognosis of CNS disorders. LncRNA H19 is correlated with susceptibility to various CNS disorders such as intracranial aneurysms, ischemic stroke, glioma, and neuroblastoma. Moreover, it participates in the pathogenesis of CNS disorders by regulating transcription, translation, and signaling pathways, suggesting that it is a promising biomarker and therapeutic target for these disorders. This article reviews the functions and mechanisms of lncRNA H19 in various CNS disorders, including cerebral ischemia, cerebral hemorrhage, glioma, pituitary adenoma, neuroblastoma, Parkinson's disease, Alzheimer's disease, traumatic spinal cord injury, neuropathic pain, and temporal lobe epilepsy, to provide a theoretical basis for further research on the role of lncRNA H19 in CNS disorders.
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21
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Wang Y, Gao WJ. Long non-coding RNA-H19 promotes ovarian cancer cell proliferation and migration via the microRNA-140/Wnt1 axis. Kaohsiung J Med Sci 2021; 37:768-775. [PMID: 34002485 DOI: 10.1002/kjm2.12393] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 03/15/2021] [Accepted: 04/25/2021] [Indexed: 02/03/2023] Open
Abstract
To explore the effect and underlying molecular mechanism of long non-coding RNA (lncRNA)-H19 on ovarian cancer (OC) cells, a total of 41 cases of OC and adjacent normal tissues were collected. H19 and microRNA (miR)-140 expressions in OC tissues and cells were detected using quantitative real-time polymerase chain reaction (qRT-RCR). The correlation between H19 expression and prognosis of OC patient was analyzed. siRNA (si)-H19 and si-negative control (NC) were transfected into OC cells. Cell proliferation was checked by cell counting kit-8 assay and colony formation assay, and cell migration and invasion were analyzed via Transwell assay. The targeted binding relationship between H19 and miR-140 was predicted and verified, miR-140 downstream gene was predicted and Wnt1 was screened out. The impact of in-miR-140 on the si-H19-induced decreased OC cell proliferation and migration was evaluated. H19 expression was upregulated in OC tissues and cells, and its overexpression was associated with a poor prognosis of OC. si-H19 remarkably reduced OC cell proliferation and migration. H19 upregulated Wnt1 expression through targeting miR-140 in OC cells. Altogether, miR-140 was notably downregulated in OC, and in-miR-140 partially inhibited the si-H19-induced decrease of OC cell proliferation and migration. H19 competitively bound to miR-140 to upregulate Wnt1, thereby promoting OC cell proliferation and migration.
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Affiliation(s)
- Ye Wang
- Department of Gynecology and Obstetrics, Aerospace Center Hospital, Beijing, China
| | - Wei-Jiao Gao
- Department of Gynecologic Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital and Institute, Beijing, China
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22
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Kim SH, Lim KH, Yang S, Joo JY. Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets. J Hematol Oncol 2021; 14:77. [PMID: 33980320 PMCID: PMC8114507 DOI: 10.1186/s13045-021-01088-0] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/03/2021] [Indexed: 12/11/2022] Open
Abstract
Brain tumors are associated with adverse outcomes despite improvements in radiation therapy, chemotherapy, and photodynamic therapy. However, treatment approaches are evolving, and new biological phenomena are being explored to identify the appropriate treatment of brain tumors. Long non-coding RNAs (lncRNAs), a type of non-coding RNA longer than 200 nucleotides, regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels and are involved in a variety of biological functions. Recent studies on lncRNAs have revealed their aberrant expression in various cancers, with distinct expression patterns associated with their instrumental roles in cancer. Abnormal expression of lncRNAs has also been identified in brain tumors. Here, we review the potential roles of lncRNAs and their biological functions in the context of brain tumors. We also summarize the current understanding of the molecular mechanisms and signaling pathways related to lncRNAs that may guide clinical trials for brain tumor therapy.
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Affiliation(s)
- Sung-Hyun Kim
- Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Key-Hwan Lim
- Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Sumin Yang
- Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Jae-Yeol Joo
- Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.
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23
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Mahinfar P, Baradaran B, Davoudian S, Vahidian F, Cho WCS, Mansoori B. Long Non-Coding RNAs in Multidrug Resistance of Glioblastoma. Genes (Basel) 2021; 12:455. [PMID: 33806782 PMCID: PMC8004794 DOI: 10.3390/genes12030455] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 03/17/2021] [Accepted: 03/19/2021] [Indexed: 12/11/2022] Open
Abstract
Glioblastoma, also known as glioblastoma multiforme, is the most aggressive brain tumor in adults. Despite the huge advance in developing novel therapeutic strategies for patients with glioblastoma, the appearance of multidrug resistance (MDR) against the common chemotherapeutic agents, including temozolomide, is considered as one of the important causes for the failure of glioblastoma treatment. On the other hand, recent studies have demonstrated the critical roles of long non-coding RNAs (lncRNAs), particularly in the development of MDR in glioblastoma. Therefore, this article aimed to review lncRNA's contribution to the regulation of MDR and elucidate the underlying mechanisms in glioblastoma, which will open up new lines of inquiry in the treatment of glioblastoma.
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Affiliation(s)
- Parvaneh Mahinfar
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5166/15731, Iran; (P.M.); (B.B.); (F.V.)
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5166/15731, Iran; (P.M.); (B.B.); (F.V.)
| | - Sadaf Davoudian
- Humanitas Clinical and Research Center—IRCCS, 20089 Milan, Italy;
| | - Fatemeh Vahidian
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5166/15731, Iran; (P.M.); (B.B.); (F.V.)
| | | | - Behzad Mansoori
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5166/15731, Iran; (P.M.); (B.B.); (F.V.)
- Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark
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24
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A HIF1A/miR-485-5p/SRPK1 axis modulates the aggressiveness of glioma cells upon hypoxia. Exp Cell Res 2021; 402:112547. [PMID: 33722639 DOI: 10.1016/j.yexcr.2021.112547] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 02/09/2021] [Accepted: 02/19/2021] [Indexed: 01/23/2023]
Abstract
The high aggressiveness of gliomas remains a huge challenge to clinical therapies, and the hypoxic microenvironment in the core region is a critical contributor to glioma aggressiveness. In this study, it was found that miR-485-5p was low expressed within glioma tissue samples and cells. GO enrichment annotation indicated that the predicted downstream targets miR-485-5p were enriched in hypoxia response and decreased oxygen level. In glioma cells, miR-485-5p overexpression suppressed cell viability, migratory ability, and invasive ability under both normoxic and hypoxic conditions. Through direct binding, miR-485-5p suppressed SRPK1 expression. Under hypoxia, SRPK1 overexpression enhanced hypoxia-induced glioma cell aggressiveness and significantly reversed the effects of miR-485-5p overexpression. Moreover, HIF1A could target the miR-485-5p promoter region to inhibit the transcription. HIF1A, miR-485-5p, and SRPK1 form a regulatory axis, which modulates glioma cell aggressiveness under hypoxia. In conclusion, we identify a HIF1A/miR-485-5p/SRPK1 axis that modulates the aggressiveness of glioma cells under hypoxia. The axis could potentially provide new research avenues in the treatment of gliomas considering the hypoxic environment in its core.
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25
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Chaudhary R. Potential of long non-coding RNAs as a therapeutic target and molecular markers in glioblastoma pathogenesis. Heliyon 2021; 7:e06502. [PMID: 33786397 PMCID: PMC7988331 DOI: 10.1016/j.heliyon.2021.e06502] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 09/20/2020] [Accepted: 03/09/2021] [Indexed: 12/14/2022] Open
Abstract
Glioblastoma (GB) is by far the most hostile type of malignant tumor that primarily affects the brain and spine, derived from star-shaped glial cells that are astrocytes and oligodendrocytes. Despite of significant efforts in recent years in glioblastoma research, the clinical efficacy of existing medical intervention is still limited and very few potential diagnostic markers are available. Long non-coding RNAs (lncRNAs) that lacks protein-coding capabilities were previously thought to be "junk sequences" in mammalian genomes are quite indispensible epigenetic regulators that can positively or negatively regulate gene expression and nuclear architecture, with significant roles in the initiation and development of tumors. Nevertheless, the precise mechanism of these distortedly expressed lncRNAs in glioblastoma pathogenesis is not yet fully understood. Since the advent of high-throughput sequencing technologies, more and more research have elucidated that lncRNAs are one of the most promising prognostic biomarkers and therapeutic targets for glioblastoma. In this paper, I briefly outlined the existing findings of lncRNAs. And also summarizes the profiles of different lncRNAs that have been broadly classified in glioblastoma research, with emphasis on both their prognostic and therapeutic values.
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Affiliation(s)
- Rishabh Chaudhary
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, U.P., India
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26
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Ebrahimpour A, Sarfi M, Rezatabar S, Tehrani SS. Novel insights into the interaction between long non-coding RNAs and microRNAs in glioma. Mol Cell Biochem 2021; 476:2317-2335. [PMID: 33582947 DOI: 10.1007/s11010-021-04080-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
Glioma is the most common brain tumor of the central nervous system. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified to play a vital role in the initiation and progression of glioma, including tumor cell proliferation, survival, apoptosis, invasion, and therapy resistance. New documents emerged, which indicated that the interaction between long non-coding RNAs and miRNAs contributes to the tumorigenesis and pathogenesis of glioma. LncRNAs can act as competing for endogenous RNA (ceRNA), and molecular sponge/deregulator in regulating miRNAs. These interactions stimulate different molecular signaling pathways in glioma, including the lncRNAs/miRNAs/Wnt/β-catenin molecular signaling pathway, the lncRNAs/miRNAs/PI3K/AKT/mTOR molecular signaling pathway, the lncRNAs-miRNAs/MAPK kinase molecular signaling pathway, and the lncRNAs/miRNAs/NF-κB molecular signaling pathway. In this paper, the basic roles and molecular interactions of the lncRNAs and miRNAs pathway glioma were summarized to better understand the pathogenesis and tumorigenesis of glioma.
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Affiliation(s)
- Anahita Ebrahimpour
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Sarfi
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Setareh Rezatabar
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Sadra Samavarchi Tehrani
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. .,Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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Katsushima K, Jallo G, Eberhart CG, Perera RJ. Long non-coding RNAs in brain tumors. NAR Cancer 2021; 3:zcaa041. [PMID: 34316694 PMCID: PMC8210177 DOI: 10.1093/narcan/zcaa041] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/09/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.
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Affiliation(s)
- Keisuke Katsushima
- Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans St., Baltimore, MD 21231, USA
| | - George Jallo
- Johns Hopkins All Children's Hospital, 600 5th St. South, St Petersburg, FL 33701, USA
| | - Charles G Eberhart
- Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans St., Baltimore, MD 21231, USA
| | - Ranjan J Perera
- Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans St., Baltimore, MD 21231, USA
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28
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Jin L, Huang S, Guan C, Chang S. ETS1-activated SNHG10 exerts oncogenic functions in glioma via targeting miR-532-3p/FBXL19 axis. Cancer Cell Int 2020; 20:589. [PMID: 33298070 PMCID: PMC7725120 DOI: 10.1186/s12935-020-01649-2] [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: 06/28/2020] [Accepted: 11/09/2020] [Indexed: 12/18/2022] Open
Abstract
Background In past few years, long non-coding RNAs (lncRNAs) have been reported to play regulatory roles during cancer progression. LncRNA SNHG10 has been explored in several sorts of cancers. However, its detailed role and mechanism are still not well understood in glioma. Methods Expression levels of genes were evaluated by RT-qPCR. EdU, TUNEL, sphere formation, wound healing and transwell assays appraised the effect of SNHG10 on glioma cellular processes. The interaction between molecules was examined by ChIP, RIP, RNA pull down and luciferase reporter assays. Results High level of SNHG10 was detected in glioma cells. Functional assay confirmed that SNHG10 promoted the proliferation, migration, invasion and stemness of glioma cells. Moreover, miR-532-3p was validated to bind with SNHG10 and expressed at a low level in glioma cells. Importantly, miR-532-3p exerted inhibitory functions in glioma. Furthermore, it was found that FBXL19 targeted by miR-532-3p facilitated cell growth and stemness in glioma, and that SNHG10 worked in glioma by increasing FBXL19 expression through sequestering miR-532-3p. More importantly, ETS1 promoted the transcription of SNHG10 and it mediated contribution to the malignant behaviors of glioma cells by SNHG10/miR-532-3p/FBXL19 signaling. Conclusion SNHG10 was transcriptionally activated by ETS1 and played an oncogenic role in glioma by sponging miR-532-3p and up-regulating FBXL19. ![]()
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Affiliation(s)
- Lide Jin
- The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming, 650032, Yunnan, China
| | - Shengquan Huang
- The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming, 650032, Yunnan, China
| | - Congjin Guan
- The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming, 650032, Yunnan, China.
| | - Shun Chang
- The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming, 650032, Yunnan, China.
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29
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Non-coding RNAs in Brain Tumors, the Contribution of lncRNAs, circRNAs, and snoRNAs to Cancer Development-Their Diagnostic and Therapeutic Potential. Int J Mol Sci 2020; 21:ijms21197001. [PMID: 32977537 PMCID: PMC7582339 DOI: 10.3390/ijms21197001] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 09/18/2020] [Accepted: 09/20/2020] [Indexed: 12/17/2022] Open
Abstract
Brain tumors are one of the most frightening ailments that afflict human beings worldwide. They are among the most lethal of all adult and pediatric solid tumors. The unique cell-intrinsic and microenvironmental properties of neural tissues are some of the most critical obstacles that researchers face in the diagnosis and treatment of brain tumors. Intensifying the search for potential new molecular markers in order to develop new effective treatments for patients might resolve this issue. Recently, the world of non-coding RNAs (ncRNAs) has become a field of intensive research since the discovery of their essential impact on carcinogenesis. Some of the most promising diagnostic and therapeutic regulatory RNAs are long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs). Many recent reports indicate the important role of these molecules in brain tumor development, as well as their implications in metastasis. In the following review, we summarize the current state of knowledge about regulatory RNAs, namely lncRNA, circRNAs, and snoRNAs, and their impact on the development of brain tumors in children and adults with particular emphasis on malignant primary brain tumors-gliomas and medulloblastomas (MB). We also provide an overview of how these different ncRNAs may act as biomarkers in these tumors and we present their potential clinical implications.
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30
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Long non-coding RNAs as epigenetic mediator and predictor of glioma progression, invasiveness, and prognosis. Semin Cancer Biol 2020; 83:536-542. [PMID: 32920124 DOI: 10.1016/j.semcancer.2020.08.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 08/28/2020] [Accepted: 08/28/2020] [Indexed: 12/21/2022]
Abstract
Gliomas are aggressive brain tumors with high mortality rate. Over the past several years, non-coding RNAs, specifically the long non-coding RNAs (lncRNAs), have emerged as biomarkers of considerable interest. Emerging data reveals distinct patterns of expressions of several lncRNAs in the glioma tissues, relative to their expression in normal brains. This has led to the speculation for putative exploitation of lncRNAs as diagnostic biomarkers as well as biomarkers for targeted therapy. With a focus on lncRNAs that have shown promise as epigenetic biomarkers in the proliferation, migration, invasion, angiogenesis and metastasis in various glioma models, we discuss several such lncRNAs. The data from cell line / animal model-based studies as well as analysis from human patient samples is presented for the most up-to-date information on the topic. Overall, the information provided herein makes a compelling case for further evaluation of lncRNAs in clinical settings.
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31
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Zhang Y, Ye F, Xiong D, Gao X. LDNFSGB: prediction of long non-coding rna and disease association using network feature similarity and gradient boosting. BMC Bioinformatics 2020; 21:377. [PMID: 32883200 PMCID: PMC7469344 DOI: 10.1186/s12859-020-03721-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 08/21/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND A large number of experimental studies show that the mutation and regulation of long non-coding RNAs (lncRNAs) are associated with various human diseases. Accurate prediction of lncRNA-disease associations can provide a new perspective for the diagnosis and treatment of diseases. The main function of many lncRNAs is still unclear and using traditional experiments to detect lncRNA-disease associations is time-consuming. RESULTS In this paper, we develop a novel and effective method for the prediction of lncRNA-disease associations using network feature similarity and gradient boosting (LDNFSGB). In LDNFSGB, we first construct a comprehensive feature vector to effectively extract the global and local information of lncRNAs and diseases through considering the disease semantic similarity (DISSS), the lncRNA function similarity (LNCFS), the lncRNA Gaussian interaction profile kernel similarity (LNCGS), the disease Gaussian interaction profile kernel similarity (DISGS), and the lncRNA-disease interaction (LNCDIS). Particularly, two methods are used to calculate the DISSS (LNCFS) for considering the local and global information of disease semantics (lncRNA functions) respectively. An autoencoder is then used to reduce the dimensionality of the feature vector to obtain the optimal feature parameter from the original feature set. Furthermore, we employ the gradient boosting algorithm to obtain the lncRNA-disease association prediction. CONCLUSIONS In this study, hold-out, leave-one-out cross-validation, and ten-fold cross-validation methods are implemented on three publicly available datasets to evaluate the performance of LDNFSGB. Extensive experiments show that LDNFSGB dramatically outperforms other state-of-the-art methods. The case studies on six diseases, including cancers and non-cancers, further demonstrate the effectiveness of our method in real-world applications.
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Affiliation(s)
- Yuan Zhang
- School of Mathematics and Computational Science, Xiangtan University, Xiangtan 411105, China
- Key Laboratory of Intelligent Computing and Information Processing of Ministry of Education, Xiangtan University, Xiangtan 411105, China
| | - Fei Ye
- Key Laboratory of Intelligent Computing and Information Processing of Ministry of Education, Xiangtan University, Xiangtan 411105, China
| | - Dapeng Xiong
- Department of Computational Biology, Ithaca, New York 14853, USA
- Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14853, USA
| | - Xieping Gao
- Key Laboratory of Intelligent Computing and Information Processing of Ministry of Education, Xiangtan University, Xiangtan 411105, China.
- College of Medical Imaging and Inspection, Xiangnan University, Chenzhou 423000, China.
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32
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Chang K, Wang G, Lou J, Hao S, Lv R, Duan D, Zhang W, Guo Y, Wang P. lncRNA TTN‑AS1 upregulates RUNX1 to enhance glioma progression via sponging miR‑27b‑3p. Oncol Rep 2020; 44:1064-1074. [PMID: 32705233 PMCID: PMC7388303 DOI: 10.3892/or.2020.7684] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 04/13/2020] [Indexed: 12/14/2022] Open
Abstract
Long non‑coding RNAs (lncRNAs) contribute to the tumorigeneses of numerous types of cancer, including glioma. The present study was designed to unveil a novel lncRNA functioning in glioma and explore the underlying mechanisms. lncRNA titin‑antisense RNA1 (TTN‑AS1), miR‑27b‑3p and Runt‑related transcription factor 1 (RUNX1) expression in glioma tissues and cell lines was estimated by RT‑qPCR. Si‑TTN‑AS1 was transfected into glioma cell lines (U251 and LN229), and CCK‑8 assay, flow cytometry, wound healing and Transwell assays were applied to estimate the function of TTN‑AS1 in glioma cells. miR‑27b‑3p inhibitor was used to explore the mechanisms. The results revealed that TTN‑AS1 was highly expressed in glioma specimens and cell lines. Downregulation of TTN‑AS1 inhibited the proliferation, migration and invasion of the glioma cells, as well as increased the rate of apoptosis. In vivo, the tumor growth was also inhibited by TTN‑AS1 depletion in nude mice. Furthermore, we revealed that TTN‑AS1 exerted oncogenic effects via sponging miR‑27b‑3p and thereby positively regulating RUNX1 expression. In conclusion, the present study supported that TTN‑AS1 acts as an oncogene in glioma by targeting miR‑27b‑3p to release RUNX1. This finding may contribute to gene therapy of glioma.
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Affiliation(s)
- Keliang Chang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Genwei Wang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Jinfeng Lou
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
| | - Sha Hao
- Department of Oncology, The Traditional Chinese Medicine Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China
| | - Ranbo Lv
- Department of Neurosurgery, Longhai Hospital of Kaifeng City, Kaifeng, Henan 475000, P.R. China
| | - Desheng Duan
- Department of Orthopaedics, The Third People's Hospital of Anyang, Anyang, Henan 455000, P.R. China
| | - Wanhong Zhang
- Department of Neurosurgery, Kaifeng Central Hospital, Kaifeng, Henan 475000, P.R. China
| | - Yingchang Guo
- Department of Intervention Therapy, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
| | - Pengfei Wang
- Department of Neurosurgery, The People's Hospital of Pingyu, Pingyu, Henan 463400, P.R. China
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Xue BZ, Xiang W, Zhang Q, Wang YH, Wang HF, Yi DY, Xiong NX, Jiang XB, Zhao HY, Fu P. Roles of long non-coding RNAs in the hallmarks of glioma. Oncol Lett 2020; 20:83. [PMID: 32863916 PMCID: PMC7436925 DOI: 10.3892/ol.2020.11944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 06/08/2020] [Indexed: 12/20/2022] Open
Abstract
Glioma is one of the most common types of tumor of the central nervous system. Due to the aggressiveness and invasiveness of high-level gliomas, the survival time of patients with these tumors is short, at ~15 months, even after combined treatment with surgery, radiotherapy and/or chemotherapy. Recently, a number of studies have demonstrated that long non-coding RNA (lncRNAs) serve crucial roles in the multistep development of human gliomas. Gliomas acquire numerous biological abilities during multistep development that collectively constitute the hallmarks of glioma. Thus, in this review, the roles of lncRNAs associated with glioma hallmarks and the current and future prospects for their development are summarized.
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Affiliation(s)
- Bing-Zhou Xue
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Wei Xiang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Qing Zhang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Yi-Hao Wang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Hao-Fei Wang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Dong-Ye Yi
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Nan-Xiang Xiong
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Xiao-Bing Jiang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Hong-Yang Zhao
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Peng Fu
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
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Long Non-Coding RNAs in Liver Cancer and Nonalcoholic Steatohepatitis. Noncoding RNA 2020; 6:ncrna6030034. [PMID: 32872482 PMCID: PMC7549373 DOI: 10.3390/ncrna6030034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/25/2020] [Accepted: 08/27/2020] [Indexed: 12/12/2022] Open
Abstract
This review aims to highlight the recent findings of long non-coding RNAs (lncRNAs) in liver disease. In particular, we focus on the functions of lncRNAs in hepatocellular carcinoma (HCC) and non-alcoholic steatohepatitis (NASH). We summarize the current research trend in lncRNAs and their potential as biomarkers and therapeutic targets for the treatment of HCC and NASH.
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35
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Li C, Zhou H. Circular RNA hsa_circRNA_102209 promotes the growth and metastasis of colorectal cancer through miR-761-mediated Ras and Rab interactor 1 signaling. Cancer Med 2020; 9:6710-6725. [PMID: 32706154 PMCID: PMC7520327 DOI: 10.1002/cam4.3332] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/05/2020] [Accepted: 07/06/2020] [Indexed: 01/02/2023] Open
Abstract
In our study, has_circRNA_102209 was the most elevated regulator in colorectal cancer (CRC) tissues according to circRNA array data. The levels of hsa_circRNA_102209 in CRC specimens and cells, as well as its effects on CRC cells were investigated. The expression of hsa_circRNA_102209 in CRC and paired non-cancerous samples, human CRC, and normal colonic epithelial cells were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cells with hsa_circRNA_102209 knockdown were established using lentiviral vectors. Cell proliferative ability was evaluated using CCK-8 assay; cell migrative/invasive activities were determined using wound healing/Transwell assay. Cell cycle arrest and apoptosis were assessed by flow cytometry; apoptosis, and EMT markers were examined using RT-qPCR and western blotting. Tumor development and levels of associated proteins were determined in hsa_circRNA_102209 knockdown mice. Our results revealed that expression of hsa_circRNA_102209 was remarkably increased in CRC tissues, where the levels of miR-761 were notably reduced (P < .05). Additionally, the levels of hsa_circRNA_102209 were associated with histology grade and occurrence of liver metastasis in CRC patients, and the expression of hsa_circRNA_102209 and miR-761 were negatively correlated (P < .05). Moreover, hsa_circRNA_102209 was upregulated in CRC cells compared with normal colonic epithelial cells. Knockdown of hsa_circRNA_102209 notably inhibited the proliferation, migration, invasion, and EMT of CRC cells (P < .05), whereas cell cycle arrest at G0/G1 phase and apoptosis were enhanced (P < .05). Furthermore, miR-761/Ras and Rab interactor 1 (RIN1) axis was the putative target of hsa_circRNA_102209 in CRC and involved in hsa_circRNA_102209-modulated growth and metastasis of CRC cells (P < .05). Knockdown of hsa_circRNA_102209 also remarkably suppressed tumor growth in vivo (P < .05). In summary, our data revealed that the expression of hsa_circRNA_102209 was elevated in CRC samples and cells. Furthermore, hsa_circRNA_102209 could promote the progression of CRC through miR-761/RIN1 axis. More importantly, hsa_circRNA_102209/miR-761/RIN1 signaling may be a novel therapeutic target for the treatment of CRC patients.
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Affiliation(s)
- Chi Li
- Department of General Surgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, P.R. China
| | - Hong Zhou
- Radiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, P.R. China
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36
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Guan N, Wang R, Feng X, Li C, Guo W. Long non-coding RNA NBAT1 inhibits the progression of glioma through the miR-21/SOX7 axis. Oncol Lett 2020; 20:3024-3034. [PMID: 32782620 DOI: 10.3892/ol.2020.11847] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 05/15/2020] [Indexed: 02/07/2023] Open
Abstract
Glioma is one of the most prevalent types of malignancy in the central nervous system worldwide, and the prognosis of patients with late stage glioma remains poor. Thus, the development of promising therapeutic strategies against glioma is essential. Long non-coding RNAs (lncRNAs) are functional RNA molecules involved in the initiation and progression of tumors, including glioma. Investigation on the regulatory roles of lncRNAs may facilitate the development of effective treatments. lncRNA NBAT1 is associated with the growth and metastasis of cancer; however, its underlying molecular mechanisms remain unknown. Thus, the present study aimed to investigate the effects of NBAT1 in glioma. The expression levels of NBAT1, microRNA (miRNA/miR)-21 and SOX7 in patients with glioma, and healthy donors using reverse transcription-quantitative PCR analysis. Human glioma cells (A172 and AM138) and normal astrocytes were used to establish the NBAT1-knockdown and overexpression models. Cell Counting Kit-8 and Transwell assays were performed to determine whether NBAT1 exerted effects on cell proliferation, migration and invasion. The results demonstrated that NBAT1 expression decreased in glioma tissues compared to normal samples. Additionally, downregulation of NBAT1 was detected in human glioma cells compared with normal astrocytes. Overexpression of NBAT1 inhibited glioma cell proliferation, migration and invasion. In addition, miR-21 was identified as a potential target of NBAT1, and the effects of miR-21-induced cell proliferation and metastasis were reversed following overexpression of NBAT1. Furthermore, SOX7 was predicted as the potential target of miR-21, and its expression was upregulated in glioma cells by overexpression of NBAT1 compared with the vehicle only control. Taken together, the results of the present study provide novel insight into the functions of NBAT1 in glioma, suggesting that the NBAT1/miR-21/SOX7 axis may act as a potential therapeutic target for the treatment of patients with glioma.
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Affiliation(s)
- Ning Guan
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
| | - Rui Wang
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
| | - Xu Feng
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
| | - Chenguang Li
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
| | - Wenshi Guo
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
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Zottel A, Šamec N, Videtič Paska A, Jovčevska I. Coding of Glioblastoma Progression and Therapy Resistance through Long Noncoding RNAs. Cancers (Basel) 2020; 12:cancers12071842. [PMID: 32650527 PMCID: PMC7409010 DOI: 10.3390/cancers12071842] [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: 05/27/2020] [Revised: 07/03/2020] [Accepted: 07/06/2020] [Indexed: 12/19/2022] Open
Abstract
Glioblastoma is the most aggressive and lethal primary brain malignancy, with an average patient survival from diagnosis of 14 months. Glioblastoma also usually progresses as a more invasive phenotype after initial treatment. A major step forward in our understanding of the nature of glioblastoma was achieved with large-scale expression analysis. However, due to genomic complexity and heterogeneity, transcriptomics alone is not enough to define the glioblastoma “fingerprint”, so epigenetic mechanisms are being examined, including the noncoding genome. On the basis of their tissue specificity, long noncoding RNAs (lncRNAs) are being explored as new diagnostic and therapeutic targets. In addition, growing evidence indicates that lncRNAs have various roles in resistance to glioblastoma therapies (e.g., MALAT1, H19) and in glioblastoma progression (e.g., CRNDE, HOTAIRM1, ASLNC22381, ASLNC20819). Investigations have also focused on the prognostic value of lncRNAs, as well as the definition of the molecular signatures of glioma, to provide more precise tumor classification. This review discusses the potential that lncRNAs hold for the development of novel diagnostic and, hopefully, therapeutic targets that can contribute to prolonged survival and improved quality of life for patients with glioblastoma.
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The LncRNA H19/miR-1-3p/CCL2 axis modulates lipopolysaccharide (LPS) stimulation-induced normal human astrocyte proliferation and activation. Cytokine 2020; 131:155106. [DOI: 10.1016/j.cyto.2020.155106] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 04/10/2020] [Accepted: 04/15/2020] [Indexed: 11/21/2022]
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Zhou R, Joshi P, Katsushima K, Liang W, Liu W, Goldenberg NA, Dover G, Perera RJ. The Emerging Field of Noncoding RNAs and Their Importance in Pediatric Diseases. J Pediatr 2020; 221S:S11-S19. [PMID: 32482229 PMCID: PMC9003624 DOI: 10.1016/j.jpeds.2020.02.078] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 02/20/2020] [Accepted: 02/27/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Rui Zhou
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins All Children's Hospital Institute for Fundamental Biomedical Research, St. Petersburg, FL.
| | - Piyush Joshi
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD,Johns Hopkins All Children’s Hospital Institute for Fundamental Biomedical Research, St. Petersburg, FL
| | - Keisuke Katsushima
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD,Johns Hopkins All Children’s Hospital Institute for Fundamental Biomedical Research, St. Petersburg, FL
| | - Weihong Liang
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD,Johns Hopkins All Children’s Hospital Institute for Fundamental Biomedical Research, St. Petersburg, FL
| | - Wei Liu
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD,Johns Hopkins All Children’s Hospital Institute for Fundamental Biomedical Research, St. Petersburg, FL
| | - Neil A. Goldenberg
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD,Johns Hopkins All Children’s Institute for Clinical and Translational Research, St. Petersburg, FL
| | - George Dover
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ranjan J. Perera
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD,Johns Hopkins All Children’s Hospital Institute for Fundamental Biomedical Research, St. Petersburg, FL
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Han W, Shi J, Cao J, Dong B, Guan W. Current advances of long non-coding RNAs mediated by wnt signaling in glioma. Pathol Res Pract 2020; 216:153008. [PMID: 32703485 DOI: 10.1016/j.prp.2020.153008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/14/2020] [Accepted: 05/10/2020] [Indexed: 12/21/2022]
Abstract
Glioma is the most common and aggressive brain tumor in the central nervous system (CNS), in which Wnt signaling pathway has been verified to play a pivotal role in regulating the initiation and progression. Currently, numerous studies have indicated that long non-coding RNAs (lncRNAs) have critical functions across biological processes including cell proliferation, colony formation, migration, invasion and apoptosis via Wnt signaling pathway in glioma. This review depicts canonical and non-canonical Wnt/β-catenin signaling pathway properties and relative processing mechanisms in gliomas, and summarizes the function and regulation of lncRNAs mediated by Wnt signaling pathway in the development and progression of glioma. Ultimately, we hope to seek out promising biomarkers and reliable therapeutic targets for glioma.
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Affiliation(s)
- Wei Han
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jia Shi
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jiachao Cao
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Bo Dong
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Wei Guan
- Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
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Long non-coding RNA H19 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by regulating microRNA-140-5p/SATB2 axis. J Biosci 2020. [DOI: 10.1007/s12038-020-0024-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Xiao Y, Zhu Z, Li J, Yao J, Jiang H, Ran R, Li X, Li Z. Expression and prognostic value of long non-coding RNA H19 in glioma via integrated bioinformatics analyses. Aging (Albany NY) 2020; 12:3407-3430. [PMID: 32081833 PMCID: PMC7066912 DOI: 10.18632/aging.102819] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 01/27/2020] [Indexed: 12/16/2022]
Abstract
Numerous discoveries have elucidated that long noncoding RNAs (lncRNAs) play a critical role in cancer malignant progression. However, their potential involvement in gliomas remains to be explored. Herein, the expression level of lncRNA H19 in glioma tissues, and its relevance with clinical characteristics were analyzed through Oncomine. The results showed that H19 was highly expressed in glioma tissues and its expression increased with the increase of malignancy. Next, GTEx and TCGA data were downloaded for differently expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the correlation analyses between H19 expression and clinic features. Radiation therapy had a good effect on glioblastoma multiforme (GBM), but didn't have a good effect on low grade glioma (LGG). Meanwhile, the expression level of H19 could act as an indicator molecule indicating the effect of radiotherapy. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted. It was found that H19 could affect the immune infiltration level of glioma through copy number variations, thus affecting the prognosis of glioma patients. Collectively, H19 may be involved in the occurrence and development of glioma, and has potential reference value for the relief and immunotherapy of glioma.
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Affiliation(s)
- Yilei Xiao
- Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng 250000, Shandong Province, P.R. China
| | - Zipeng Zhu
- Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng 250000, Shandong Province, P.R. China
| | - Jianxiong Li
- Department of Chemotherapy, Chinese PLA General Hospital, Beijing 100036, P.R. China
| | - Jie Yao
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, P.R. China
| | - Haitao Jiang
- Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng 250000, Shandong Province, P.R. China
| | - Ran Ran
- Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng 250000, Shandong Province, P.R. China
| | - Xueyuan Li
- Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng 250000, Shandong Province, P.R. China
| | - Zhiqiang Li
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, P.R. China
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Correlation between polymorphisms in IGF2/H19 gene locus and epithelial ovarian cancer risk in Chinese population. Genomics 2020; 112:2510-2515. [PMID: 32045670 DOI: 10.1016/j.ygeno.2020.02.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 12/29/2019] [Accepted: 02/07/2020] [Indexed: 01/14/2023]
Abstract
To investigate the association between SNPs in human IGF2/H19 gene locus and epithelial ovarian cancer (EOC) risk, we performed a case-control study in 422 individuals (219 EOC patients and 203 cancer-free controls). Four SNPs (rs2525885, rs2839698, rs3741206, rs3741219) were found to be related with EOC risk. Specifically, the minor allele C of rs2525885 and allele A of rs2839698 was associated with elevated EOC genetic susceptibility under both dominant and recessive models (TC + CC vs TT: adjusted OR: 1.61, P = .031; CC vs TT + TC: adjusted OR: 4.87, P = .014; GA + AA vs GG: adjusted OR: 1.63, P = .023; AA vs GG + GA: adjusted OR: 2.43, P = .007). For rs3741206, the genotype TC + CC was associated with a significant decrease in EOC risk with the TT genotype as reference in a dominant genetic model (adjusted OR: 0.44, P = .003), while for rs3741219, genotype AA was associated with a 59% decrease in EOC risk only in the recessive model (adjusted OR: 0.41, P = .038). In the stratified analysis, an increased risk associated with the variant genotypes was observed in only subjects aged >47 years for rs2525885 (adjusted OR = 2.04, P = .024), rs2839698 (adjusted OR = 2.50, P = .047) and rs3741206 (adjusted OR = 0.37, P = .009), respectively. What's more, the TC + CC genotype of rs2525885 was significantly associated with advanced FIGO stage (III vs II, adjusted OR = 2.73, P = .040).
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Li Y, Guo D. Identification of Novel lncRNA Markers in Glioblastoma Multiforme and Their Clinical Significance: A Study Based on Multiple Sequencing Data. Onco Targets Ther 2020; 13:1087-1098. [PMID: 32099410 PMCID: PMC7007783 DOI: 10.2147/ott.s235951] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/22/2020] [Indexed: 12/13/2022] Open
Abstract
Background Long non-coding RNAs (lncRNAs) have been verified to have a vital role in the progression of glioblastoma multiforme (GBM). Our research was about to identify the potential lncRNAs which was closely associated with the pathogenesis and prognosis of glioblastoma multiforme. Methods All RNA sequence profiling data from patients with GBM were obtained from The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA). Differently expressed genes identified from GBM and control samples were used to construct competing endogenous RNA (ceRNA) network and perform corresponding functional enrichment analysis. Univariate Cox regression followed by lasso regression and multivariate Cox was used to validate independent lncRNA factors and construct a risk prediction model. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression levels of potential lncRNA biomarkers in human GBM clinical specimens. A gene set enrichment analysis (GSEA) was subsequently conducted to explore potential signaling pathways in which critical lncRNAs may be involved. Moreover, nomogram plot was applied based on our prediction model and significant clinical covariates to visualize the prognosis of GBM patients. Results A total of 2023 differentially expressed genes (DEGs) including 56 lncRNAs, 1587 message RNAs (mRNAs) and 380 other RNAs were included. Based on predictive databases, 16lncRNAs, 32 microRNAs (miRNAs) and 99 mRNAs were used to construct a ceRNA network. Moreover, we performed a novel risk prediction model with 5 potential prognostic lncRNAs, in which 4 of them were newly identified in GBM, to predict the prognosis of GBM patients. Finally, a nomogram plot was constructed to illustrate the potential relationship between the prognosis of GBM and our risk prediction model and significant clinical covariates. Conclusion In this study, we identified 4 novel potential lncRNA biomarkers and constructed a prediction model of GBM prognosis. A simple-to-use nomogram was provided for further clinical application.
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Affiliation(s)
- Youwei Li
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Dongsheng Guo
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
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Zhou H, Zhang Y, Lai Y, Xu C, Cheng Y. Circ_101064 regulates the proliferation, invasion and migration of glioma cells through miR-154-5p/ PIWIL1 axis. Biochem Biophys Res Commun 2020; 523:608-614. [PMID: 31941603 DOI: 10.1016/j.bbrc.2019.12.096] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 12/21/2019] [Indexed: 02/06/2023]
Abstract
This study aimed to investigate the effects of Circ_101064 on glioma cell proliferation, invasion, migration and explore the underlying mechanisms. The expression levels of Circ_101064 in glioma/para-carcinoma tissues and glioma cells were analyzed using RT-qPCR. Moreover, U251 and U87 cells were transfected with si-Circ_101064 or miR-154-5p mimics. Cell proliferation rate was determined by CCK-8 assay; the invasion and migration activities were examined using Transwell assay; the expression levels of PIWIL1 were evaluated by RT-qPCR and western blotting. The expression level of Circ_101064 was significantly upregulated in glioma tissues compared with control, and was closely associated with tumor grading and diameter. Furthermore, increased Circ_101064 expression was detected in human glioma cell lines. In addition, knockdown of Circ_101064 remarkably suppressed cell proliferation, invasion and migration in glioma cells in vitro. Moreover, microRNA-154-5p (miR-154-5p) could be a target of Circ_101064. Additionally, PIWIL1 is a putative downstream molecule of miR-154-5p, and its expression was downregulated by knockdown of Circ_101064. The effects on cell growth and metastasis caused by si-Circ_101064 were notably enhanced by miR-154-5p mimics. However, the influences of miR-154-5p-suppressed proliferation, migration and invasion of glioma cells could be abolished by overexpressed PIWIL1. In summary, our findings provided novel insight into the regulatory functions of Circ_101064 during tumor development in glioma. More importantly, Circ_101064/miR-154-5p/PIWIL1 axis could be a promising therapeutic target for the treatment of this disease.
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Affiliation(s)
- Hongjun Zhou
- Department of Neurological Diseases, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China
| | - Yundong Zhang
- Department of Neurological Diseases, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China
| | - Yujie Lai
- Department of Neurological Diseases, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China
| | - Chu Xu
- Department of Neurological Diseases, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China
| | - Yuanyuan Cheng
- Department of Neurological Diseases, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, PR China.
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Zhang S, Qin W, Yang S, Guan N, Sui X, Guo W. Circular RNA SFMBT2 Inhibits the Proliferation and Metastasis of Glioma Cells Through Mir-182-5p/Mtss1 Pathway. Technol Cancer Res Treat 2020; 19:1533033820945799. [PMID: 32729377 PMCID: PMC7394026 DOI: 10.1177/1533033820945799] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 06/02/2020] [Accepted: 06/30/2020] [Indexed: 01/05/2023] Open
Abstract
Glioma is a common type of tumor in human central nervous system, and it is characterized with high mobility and mortality. The prognosis of patients with advanced glioma remains poor. Thus, it is necessary to develop novel therapeutic approaches for the treatment of this disease. Circular RNAs are a group of noncoding RNAs which have been detected in eukaryotic cells. They are tissue-specific and characterized with a more stable structure compared with linear RNAs. Recently, studies have revealed that certain circular RNAs are involved in biological processes such as gene regulation; however, the functions of most circular RNAs remain unknown and require further investigation. Furthermore, circular RNAs can act as "sponges" of its target microRNA, consequently suppressing their activity. Additionally, impaired expression of circular RNAs is reported in different diseases including cancer. In our study, low expression of circular RNA Scm like with 4 Mbt domains 2 was detected in glioma samples. Furthermore, reduced circRNA Scm like with 4 Mbt domains 2 expression was observed in human glioma cell lines compared to normal astrocyte cells. Additionally, overexpression of circRNA Scm like with 4 Mbt domains 2 suppressed the growth and metastasis of glioma cells in vitro. Moreover, microRNA-182-5p could be a downstream molecule of circRNA Scm like with 4 Mbt domains 2. The influenced of microRNA-182-5p-induced proliferation, migration, and invasion of glioma cells could be abrogated by overexpressed circRNA Scm like with 4 Mbt domains 2. In addition, metastasis suppressor 1 was predicted as a novel target of microRNA-182-5p, and its expression was restored by circRNA Scm like with 4 Mbt domains 2. In summary, our findings provided novel insight into the roles of circRNA Scm like with 4 Mbt domains 2 in glioma. More importantly, circRNA Scm like with 4 Mbt domains 2/microRNA-182-5p/metastasis suppressor 1 axis could be a putative therapeutic target for the treatment of patients with glioma.
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Affiliation(s)
- Shoudan Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China
| | - Wanxiang Qin
- Department of Pain Care, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Shuo Yang
- Cadet Brigade, Army Medical University, Chongqing, People’s Republic of China
| | - Ning Guan
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China
| | - Xin Sui
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China
| | - Wenshi Guo
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China
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Shi S, Li D, Li Y, Feng Z, Du Y, Nie Y. LncRNA CR749391 acts as a tumor suppressor to upregulate KLF6 expression via interacting with miR-181a in gastric cancer. Exp Ther Med 2019; 19:569-578. [PMID: 31853323 PMCID: PMC6909595 DOI: 10.3892/etm.2019.8226] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 11/30/2018] [Indexed: 01/22/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are novel regulators for post-transcriptional gene expression, and altered lncRNAs function and expression are associated with tumorigenesis and cancer progression, although the biological functions of most lncRNAs in various cancer types and their underlying regulatory interactions have remained largely elusive. Our previous study identified microRNA (miR)-181a as a regulator of Kruppel-like factor 6 (KLF6). In the present study, a bioinformatical analysis was performed to identify the novel lncRNA CR749391 as a potential regulator of miR-181a that contains four putative binding sites. Subsequent in vitro experiments in gastric cancer (GC) cells demonstrated that CR749391 interacted with miR-181a to regulate KLF6 expression. First, a direct binding interaction was confirmed using luciferase reporter and RNA immunoprecipitation and pull-down assays. In addition, CR749391 was observed to be downregulated in GC compared with that of normal gastric cell lines. A functional study also revealed that CR749391 depletion in normal gastric epithelial cells promoted cell viability, migration and invasion, and conferred resistance to apoptosis, whereas ectopic CR749391 overexpression had the opposite effect in GC cells and inhibited in vivo tumor growth. In addition, CR749391 was observed to be downregulated in GC compared with that of normal gastric tissues, which was associated with KLF6 but inversely associated with miR-181a levels. Overall, the CR749391/miR-181a regulatory interaction and association between CR749391 and KLF6 may enhance the current understanding of GC pathogenesis, although CR749391 association with GC prognosis needs further study. The current study could provide a novel approach for lncRNA-mediated targeted GC therapy.
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Affiliation(s)
- Shengli Shi
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.,Department of Gastroenterology, Xiaolan People's Hospital of Southern Medical University, Zhangshan, Guangdong 528415, P.R. China
| | - Defeng Li
- Department of Gastroenterology, The 2nd Clinical Medicine College (Shenzhen People's Hospital) of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Yingfei Li
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Zhiqiang Feng
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yanlei Du
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
| | - Yuqiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China
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Yang H, Peng M, Li Y, Zhu R, Li X, Qian Z. LINC00703 Acts as a Tumor Suppressor via Regulating miR-181a/KLF6 Axis in Gastric Cancer. J Gastric Cancer 2019; 19:460-472. [PMID: 31897348 PMCID: PMC6928083 DOI: 10.5230/jgc.2019.19.e43] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/24/2019] [Accepted: 11/25/2019] [Indexed: 12/15/2022] Open
Abstract
Purpose Long noncoding RNA 00703 (LINC00703) was found originating from a region downstream of Kruppel-like factor 6 (KLF6) gene, having 2 binding sites for miR-181a. Since KLF6 has been reported as a target of miR-181a in gastric cancer (GC), this study aims to investigate whether LINC00703 regulates the miR-181a/KLF6 axis and plays a functional role in GC pathogenesis. Materials and Methods GC tissues, cell lines, and nude mice were included in this study. RNA binding protein immunoprecipitation (RIP) and pull-down assays were used to evaluate interaction between LINC00703 and miR-181a. Quantitative real-time polymerase chain reaction and western blot were applied for analysis of gene expression at the transcriptional and protein levels. A nude xenograft mouse model was used to determine LINC00703 function in vivo. Results We revealed that LINC00703 competitively interacts with miR-181a to regulate KLF6. Overexpression of LINC00703 inhibited cell proliferation, migration/invasion, but promoted apoptosis in vitro, and arrested tumor growth in vivo. LINC00703 expression was found to be decreased in GC tissues, which was positively correlated with KLF6, but negatively with the miR-181a levels. Conclusions LINC00703 may have an anti-cancer function via modulation of the miR-181a/KLF6 axis. This study also provides a new potential diagnostic marker and therapeutic target for GC treatment.
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Affiliation(s)
- Haiyang Yang
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Minqi Peng
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Yanjiao Li
- Department of Pathophysiology, Shenzhen University, Shenzhen, China
| | - Renjie Zhu
- East Hospital Affiliated to Tongji University, Shanghai, China
| | - Xiang Li
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Zhengjiang Qian
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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Li L, Wei J, Hei J, Ren Y, Li H. Long non-coding RNA H19 regulates proliferation of ovarian granulosa cells via STAT3 in polycystic ovarian syndrome. Arch Med Sci 2019; 17:785-791. [PMID: 34025849 PMCID: PMC8130457 DOI: 10.5114/aoms.2019.89254] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 07/18/2019] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Studies have shown that long non-coding RNAs (lncRNA) are aberrantly expressed in polycystic ovarian syndrome (PCOS) ovaries and may have a role in PCOS development. In this study, the role and therapeutic implications of lncRNA H19 were investigated in PCOS ovaries and granulosa cells. MATERIAL AND METHODS qRT-PCR was used for expression analysis. Cell Counting Kit 8 (CCK-8) assay was used for cell viability and acridine orange/ethidium bromide (AO/EB) and Annexin V/propidium iodide staining was used to detect apoptosis. All transfections were carried out with Lipofectamine 2000 reagent. Western blot analysis was used for protein expression analysis. RESULTS The expression of lncRNA H19 was remarkably upregulated in the PCOS ovarian tissues as well as the granulosa cells. Suppression of lncRNA H19 expression caused the inhibition of KGN granulosa cell proliferation due to the triggering of apoptosis. Bioinformatic analysis revealed the presence of the GAS binding site for STAT3 in the promoter of lncRNA H19. Silencing of STAT3 suppressed the expression of lncRNA H19 in KGN cells and also halted their growth by triggering apoptosis. Co-transfect experiments revealed that STAT3 and lncRNA H19 silencing cause inhibition of KGN growth synergistically. CONCLUSIONS lncRNA H19 regulates the growth of ovarian granulosa cells and might prove to be a therapeutic target for management of PCOS.
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Affiliation(s)
- Li Li
- Department of Obstetrics, Yanan University Affiliated Hospital, Yan'an, China
| | - Jianxun Wei
- Department of Obstetrics, Yanan University Affiliated Hospital, Yan'an, China
| | - Jiangrong Hei
- Department of Obstetrics, Yanan University Affiliated Hospital, Yan'an, China
| | - Yongbian Ren
- Department of Obstetrics, Yanan University Affiliated Hospital, Yan'an, China
| | - Hongmei Li
- Department of Obstetrics, Yanan University Affiliated Hospital, Yan'an, China
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Janaki Ramaiah M, Divyapriya K, Kartik Kumar S, Rajesh YBRD. Drug-induced modifications and modulations of microRNAs and long non-coding RNAs for future therapy against Glioblastoma Multiforme. Gene 2019; 723:144126. [PMID: 31589963 DOI: 10.1016/j.gene.2019.144126] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 09/11/2019] [Accepted: 09/12/2019] [Indexed: 02/07/2023]
Abstract
Non-coding RNAs are known to participate in cancer initiation, progression, and metastasis by regulating the status of chromatin epigenetics and gene expression. Although these non-coding RNAs do not possess defined protein-coding potential, they are involved in the expression and stability of messenger RNA (mRNA). The length of microRNAs (miRs) ranges between 20 and 22 nt, whereas, long non-coding RNAs (lncRNAs) length ranges between 200 nt to 1 Kb. In the case of circular RNAs (circRNAs), the size varies depending upon the length of the exon from where they were derived. Epigenetic regulations of miR and lncRNA genes will influence the gene expression by modulating histone acetylation and methylation patterns. Especially, lncRNAs will act as a scaffold for various epigenetic proteins, such as EZH2 and LSD1, and influence the chromatin epigenetic state at various genomic loci involved at silencing. Thus investigations on the expression of lncRNAs and designing drugs to modulate the expression of these genes will have a profound impact on future therapeutics against cancers such as Glioblastoma Multiforme (GBM) and also against various other diseases. With the recent advancements in genome-wide transcriptomic studies, scientists are focused on the non-coding RNAs and their regulations on various cellular processes involved in GBM and on other types of cancer as well as trying to understand possible epigenetic modulations that help in generating promising therapeutics for the future generations. In this review, the involvement of epigenetic proteins, enzymes that change chromatin architecture and epigenetic landscape and new roles of lncRNAs that are involved in GBM progression are elaborately discussed.
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Affiliation(s)
- M Janaki Ramaiah
- Laboratory of Functional Genomics and Disease Biology, School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.
| | - Karthikeyan Divyapriya
- Laboratory of Functional Genomics and Disease Biology, School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur 613401, Tamil Nadu, India
| | - Sarwareddy Kartik Kumar
- Laboratory of Functional Genomics and Disease Biology, School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur 613401, Tamil Nadu, India
| | - Y B R D Rajesh
- Organic Synthesis and Catalysis Laboratory, School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur 613401, Tamil Nadu, India
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