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1
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Wang G, Yao Y, Xie J, Wen C. Long noncoding RNA ZFAS1 exerts a suppressive impact on ferroptosis by modulating the miR-150/AIFM2 axis in hepatocellular carcinoma cells. Heliyon 2024; 10:e37225. [PMID: 39296014 PMCID: PMC11409106 DOI: 10.1016/j.heliyon.2024.e37225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 08/27/2024] [Accepted: 08/29/2024] [Indexed: 09/21/2024] Open
Abstract
ZNFX1 Antisense RNA 1 (ZFAS1) act as an oncogenic long noncoding RNA in multiple types of cancer. Ferroptosis is an iron-dependent cell death characterized by excessive iron accumulation and lipid peroxidation. However, to date, the functional role and mechanism of ZFAS1 in ferroptosis in hepatocellular carcinoma (HCC) remains largely unknown. The present study revealed that ZFAS1 was upregulated in HCC and upregulation of ZFAS1 indicated poor clinical outcome of HCC patients. Loss- and gain-of-function experiments demonstrated that knockdown of ZFAS1 inhibited HCC cell proliferation and induced ferroptosis, while overexpression of ZFAS1 exerted opposite effects. ZFAS1 enhanced cell proliferation via suppression of ferroptotic death. Mechanistically, ZFAS1 interacted with miR-150 and decreased its expression. AIFM2, the critical ferroptosis protector, was a direct target of ZFAS1/miR-150. ZFAS1 accelerated HCC proliferation and inhibited ferroptosis by the regulation of the miR-150/AIFM2 axis. These discoveries intimate an essential part of ZFAS1/miR-150/AIFM2 in governing HCC ferroptosis, which may provide a promising therapeutic strategy for HCC patients.
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Affiliation(s)
- Guangsheng Wang
- Department of Gastrointestinal surgery, The First Clinical Medical College of China Three Gorges University, China
| | - Yongshan Yao
- Department of Emergency surgery, The First Clinical Medical College of China Three Gorges University, China
| | - Jiasheng Xie
- Department of General surgery, Xiling Community Health Service Center, Xiling District, Yichang City, China
| | - Caihong Wen
- Department of Medical oncology, The First Clinical Medical College of China Three Gorges University, China
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2
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Mathias C, Rodrigues AC, Baal SCS, de Azevedo ALK, Kozak VN, Alves LF, de Oliveira JC, Guil S, Gradia DF. The landscape of lncRNAs in cell granules: Insights into their significance in cancer. WILEY INTERDISCIPLINARY REVIEWS. RNA 2024; 15:e1870. [PMID: 39268566 DOI: 10.1002/wrna.1870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 08/22/2024] [Accepted: 08/27/2024] [Indexed: 09/17/2024]
Abstract
Cellular compartmentalization, achieved through membrane-based compartments, is a fundamental aspect of cell biology that contributes to the evolutionary success of cells. While organelles have traditionally been the focus of research, membrane-less organelles (MLOs) are emerging as critical players, exhibiting distinct morphological features and unique molecular compositions. Recent research highlights the pivotal role of long noncoding RNAs (lncRNAs) in MLOs and their involvement in various cellular processes across different organisms. In the context of cancer, dysregulation of MLO formation, influenced by altered lncRNA expression, impacts chromatin organization, oncogenic transcription, signaling pathways, and telomere lengthening. This review synthesizes the current understanding of lncRNA composition within MLOs, delineating their functions and exploring how their dysregulation contributes to human cancers. Environmental challenges in tumorigenesis, such as nutrient deprivation and hypoxia, induce stress granules, promoting cancer cell survival and progression. Advancements in biochemical techniques, particularly single RNA imaging methods, offer valuable tools for studying RNA functions within live cells. However, detecting low-abundance lncRNAs remains challenging due to their limited expression levels. The correlation between lncRNA expression and pathological conditions, particularly cancer, should be explored, emphasizing the importance of single-cell studies for precise biomarker identification and the development of personalized therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
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Affiliation(s)
- Carolina Mathias
- Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba, PR, Brazil
| | - Ana Carolina Rodrigues
- Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba, PR, Brazil
| | - Suelen Cristina Soares Baal
- Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba, PR, Brazil
| | | | - Vanessa Nascimento Kozak
- Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba, PR, Brazil
| | | | | | - Sonia Guil
- Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Catalonia, Spain
| | - Daniela Fiori Gradia
- Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba, PR, Brazil
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3
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Zhang Y, Yu Z, Wong KC, Li X. Unraveling Spatial Domain Characterization in Spatially Resolved Transcriptomics with Robust Graph Contrastive Clustering. Bioinformatics 2024; 40:btae451. [PMID: 39012523 PMCID: PMC11272174 DOI: 10.1093/bioinformatics/btae451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 06/12/2024] [Accepted: 07/12/2024] [Indexed: 07/17/2024] Open
Abstract
MOTIVATION Spatial transcriptomics can quantify gene expression and its spatial distribution in tissues, thus revealing molecular mechanisms of cellular interactions underlying tissue heterogeneity, tissue regeneration, and spatially localized disease mechanisms. However, existing spatial clustering methods often fail to exploit the full potential of spatial information, resulting in inaccurate identification of spatial domains. RESULTS In this paper, we develop a deep graph contrastive clustering framework, stDGCC, that accurately uncovers underlying spatial domains via explicitly modeling spatial information and gene expression profiles from spatial transcriptomics data. The stDGCC framework proposes a spatially informed graph node embedding model to preserve the topological information of spots and to learn the informative and discriminative characterization of spatial transcriptomics data through self-supervised contrastive learning. By simultaneously optimizing the contrastive learning loss, reconstruction loss, and Kullback-Leibler (KL) divergence loss, stDGCC achieves joint optimization of feature learning and topology structure preservation in an end-to-end manner. We validate the effectiveness of stDGCC on various spatial transcriptomics datasets acquired from different platforms, each with varying spatial resolutions. Our extensive experiments demonstrate the superiority of stDGCC over various state-of-the-art clustering methods in accurately identifying cellular-level biological structures. AVAILABILITY Code and data are available from https://github.com/TimE9527/stDGCC and https://figshare.com/projects/stDGCC/186525. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- Yingxi Zhang
- School of Artificial Intelligence, Jilin University, Changchun 130012, China
| | - Zhuohan Yu
- School of Artificial Intelligence, Jilin University, Changchun 130012, China
| | - Ka-Chun Wong
- Department of Computer Science, City University of Hong Kong, Hong Kong 999077, Hong Kong SAR
| | - Xiangtao Li
- School of Artificial Intelligence, Jilin University, Changchun 130012, China
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4
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Xu D, Wang W, Wang D, Ding J, Zhou Y, Zhang W. Long noncoding RNA MALAT-1: A versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance. Noncoding RNA Res 2024; 9:388-406. [PMID: 38511067 PMCID: PMC10950606 DOI: 10.1016/j.ncrna.2024.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/24/2024] [Accepted: 01/24/2024] [Indexed: 03/22/2024] Open
Abstract
Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that do not code for proteins but have been linked to cancer development and metastasis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) influences crucial cancer hallmarks through intricate molecular mechanisms, including proliferation, invasion, angiogenesis, apoptosis, and the epithelial-mesenchymal transition (EMT). The current article highlights the involvement of MALAT-1 in drug resistance, making it a potential target to overcome chemotherapy refractoriness. It discusses the impact of MALAT-1 on immunomodulatory molecules, such as major histocompatibility complex (MHC) proteins and PD-L1, leading to immune evasion and hindering anti-tumor immune responses. MALAT-1 also plays a significant role in cancer immunology by regulating diverse immune cell populations. In summary, MALAT-1 is a versatile cancer regulator, influencing tumorigenesis, chemoresistance, and immunotherapy responses. Understanding its precise molecular mechanisms is crucial for developing targeted therapies, and therapeutic strategies targeting MALAT-1 show promise for improving cancer treatment outcomes. However, further research is needed to fully uncover the role of MALAT-1 in cancer biology and translate these findings into clinical applications.
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Affiliation(s)
- Dexin Xu
- Department of Orthopedics, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Wenhai Wang
- Department of Cardiology, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Duo Wang
- Department of Geriatrics, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Jian Ding
- Department of Electrodiagnosis, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Yunan Zhou
- Department of Orthopedics, Jilin Province FAW General Hospital, Changchun, 130000, China
| | - Wenbin Zhang
- Department of Cardiology, Jilin Province FAW General Hospital, Changchun, 130000, China
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Zhang Y, Lu Y, Wang N, Yang Y, Hao F, Fei X, Chen Y, Wang J. Alternative splicing-related long noncoding RNA ANRIL facilitates hepatocellular carcinoma by targeting the miR-199a-5p/SRSF1 axis and impacting Anillin. Mol Carcinog 2024; 63:1064-1078. [PMID: 38411272 DOI: 10.1002/mc.23709] [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: 10/07/2023] [Revised: 01/27/2024] [Accepted: 02/12/2024] [Indexed: 02/28/2024]
Abstract
Hepatocellular carcinoma (HCC) is characterized by aberrant alternative splicing (AS), which plays an important part in the pathological process of this disease. However, available reports about genes and mechanisms involved in AS process are limited. Our previous research has identified ANRIL as a long noncoding RNA related to the AS process of HCC. Here, we investigated the exact effect and the mechanism of ANRIL on HCC progress. The ANRIL expression profile was validated using the real-time quantitative polymerase chain reaction assay. The western blot analysis and IHC assay were conducted on candidate targets, including SRSF1 and Anillin. The clinicopathological features of 97 patients were collected and analyzed. Loss-of and gain-of-function experiments were conducted. The dual-luciferase reporter assay was applied to verify the interaction between ANRIL, miR-199a-5p, and SRSF1. Anomalous upregulation of ANRIL in HCC was observed, correlating with worse clinicopathological features of HCC. HCC cell proliferation, mobility, tumorigenesis, and metastasis were impaired by depleting ANRIL. We found that ANRIL acts as a sponger of miRNA-199a-5p, resulting in an elevated level of its target protein SRSF1. The phenotypes induced by ANRIL/miR-199a-5p/SRSF1 alteration are associated with Anillin, a validated HCC promoter. ANRIL is an AS-related lncRNA promoting HCC progress by modulating the miR-199a-5p/SRSF1 axis. The downstream effector of this axis in the development of HCC is Anillin.
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Affiliation(s)
- Yifan Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yiquan Lu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Nan Wang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yuchen Yang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Fengjie Hao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Xiaochun Fei
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yongjun Chen
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Junqing Wang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
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6
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Khan MM, Kirabo A. Long Noncoding RNA MALAT1: Salt-Sensitive Hypertension. Int J Mol Sci 2024; 25:5507. [PMID: 38791545 PMCID: PMC11122212 DOI: 10.3390/ijms25105507] [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: 03/14/2024] [Revised: 05/06/2024] [Accepted: 05/15/2024] [Indexed: 05/26/2024] Open
Abstract
Hypertension stands as the leading global cause of mortality, affecting one billion individuals and serving as a crucial risk indicator for cardiovascular morbidity and mortality. Elevated salt intake triggers inflammation and hypertension by activating antigen-presenting cells (APCs). We found that one of the primary reasons behind this pro-inflammatory response is the epithelial sodium channel (ENaC), responsible for transporting sodium ions into APCs and the activation of NADPH oxidase, leading to increased oxidative stress. Oxidative stress increases lipid peroxidation and the formation of pro-inflammatory isolevuglandins (IsoLG). Long noncoding RNAs (lncRNAs) play a crucial role in regulating gene expression, and MALAT1, broadly expressed across cell types, including blood vessels and inflammatory cells, is also associated with inflammation regulation. In hypertension, the decreased transcriptional activity of nuclear factor erythroid 2-related factor 2 (Nrf2 or Nfe2l2) correlates with heightened oxidative stress in APCs and impaired control of various antioxidant genes. Kelch-like ECH-associated protein 1 (Keap1), an intracellular inhibitor of Nrf2, exhibits elevated levels of hypertension. Sodium, through an increase in Sp1 transcription factor binding at its promoter, upregulates MALAT1 expression. Silencing MALAT1 inhibits sodium-induced Keap1 upregulation, facilitating the nuclear translocation of Nrf2 and subsequent antioxidant gene transcription. Thus, MALAT1, acting via the Keap1-Nrf2 pathway, modulates antioxidant defense in hypertension. This review explores the potential role of the lncRNA MALAT1 in controlling the Keap1-Nrf2-antioxidant defense pathway in salt-induced hypertension. The inhibition of MALAT1 holds therapeutic potential for the progression of salt-induced hypertension and cardiovascular disease (CVD).
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Affiliation(s)
- Mohd Mabood Khan
- Department of Medicine, Preston Research Building, Vanderbilt University Medical Centre, Nashville, TN 37232, USA
| | - Annet Kirabo
- Department of Medicine, Preston Research Building, Vanderbilt University Medical Centre, Nashville, TN 37232, USA
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Shafaee Arani S, Nejati M, Rastgoufar S, Raisi A, Eshraghi R, Ostadian A, Matini AH, Rahimain N, Mirzaei H. Evaluation of expression level of BANCR, MALAT1 and FER1L4 and their target genes in coumarin-treated AGS cell line. Pathol Res Pract 2024; 257:155291. [PMID: 38643553 DOI: 10.1016/j.prp.2024.155291] [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: 02/01/2024] [Revised: 03/23/2024] [Accepted: 04/02/2024] [Indexed: 04/23/2024]
Abstract
Because long non-coding RNAs (lncRNAs) can affect several interconnected processes, its value as a predictive marker for gastric cancer has been demonstrated. Coumarin - a natural compound known to contain some beneficial antitumor qualities - was tested for its effects on AGS gastric cancer cells. In this study, we investigated the expression level of selected cellular lncRNAs (BANCR, MALAT1 and FER1L4) and their target genes (PTEN, p-PI3K and p-AKT) in coumarin-treated AGS cell line. The expressions of the three lncRNAs: BANCR, MALAT1 and FER1L4, as well as their specified targets, PTEN, PI3K and AKT, were measured by qRT-PCR. To gauge the impact of coumarin on the AGS cells, a MTT assay was utilized. A Western blot has been employed to assess variations in PTEN, p-PI3K, and p-AKT expression. The experiment's results showed that AGS viability diminished with increasing doses of coumarin. Compared to the control cells, the cells exposed to coumarin had showed reduced levels of mRNAs which are known targets of the lncRNA BANCR. At the same time, levels of lncRNAs MALAT1 and FER1L4 within coumarin group have been higher comparing to those within control group. Additionally, the Western blot analysis revealed that the coumarin-treated cells expressed lower levels of p-PI3K, PTEN as well as p-AKT compared to control group. This information points to coumarin being a possible option in a treatment regimen for gastric cancer due to its ability to affect lncRNAs and the molecules they target.
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Affiliation(s)
- Shirin Shafaee Arani
- Department of Pathology and Histology, School of Medicine, Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran
| | - Majid Nejati
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Sepide Rastgoufar
- Department of Pathology and Histology, School of Medicine, Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran
| | - Arash Raisi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Reza Eshraghi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Amirreza Ostadian
- Department of Laboratory Medicine, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Amir Hassan Matini
- Department of Pathology and Histology, School of Medicine, Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran.
| | - Neda Rahimain
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Internal Medicine, School of Medicine, Firoozgar Hospital, 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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Piórkowska K, Zygmunt K, Hunter W, Wróblewska K. MALAT1: A Long Non-Coding RNA with Multiple Functions and Its Role in Processes Associated with Fat Deposition. Genes (Basel) 2024; 15:479. [PMID: 38674413 PMCID: PMC11049917 DOI: 10.3390/genes15040479] [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: 03/13/2024] [Revised: 04/05/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) belongs to the lncRNA molecules, which are involved in transcriptional and epigenetic regulation and the control of gene expression, including the mechanism of chromatin remodeling. MALAT1 was first discovered during carcinogenesis in lung adenocarcinoma, hence its name. In humans, 66 of its isoforms have been identified, and in pigs, only 2 are predicted, for which information is available in Ensembl databases (Ensembl Release 111). MALAT1 is expressed in numerous tissues, including adipose, adrenal gland, heart, kidney, liver, ovary, pancreas, sigmoid colon, small intestine, spleen, and testis. MALAT1, as an lncRNA, shows a wide range of functions. It is involved in the regulation of the cell cycle, where it has pro-proliferative effects and high cellular levels during the G1/S and mitotic (M) phases. Moreover, it is involved in invasion, metastasis, and angiogenesis, and it has a crucial function in alternative splicing during carcinogenesis. In addition, MALAT1 plays a significant role in the processes of fat deposition and adipogenesis. The human adipose tissue stem cells, during differentiation into adipocytes, secrete MALAT1 as one the most abundant lncRNAs in the exosomes. MALAT1 expression in fat tissue is positively correlated with adipogenic FABP4 and LPL. This lncRNA is involved in the regulation of PPARγ at the transcription stage, fatty acid metabolism, and insulin signaling. The wide range of MALAT1 functions makes it an interesting target in studies searching for drugs to prevent obesity development in humans. In turn, in farm animals, it can be a source of selection markers to control the fat tissue content.
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Affiliation(s)
- Katarzyna Piórkowska
- National Research Institute of Animal Production, Animal Molecular Biology, 31-047 Cracow, Poland; (K.Z.); (K.W.)
| | - Karolina Zygmunt
- National Research Institute of Animal Production, Animal Molecular Biology, 31-047 Cracow, Poland; (K.Z.); (K.W.)
| | - Walter Hunter
- Faculty of Biotechnology and Horticulture, University of Agriculture in Cracow, 31-120 Cracow, Poland;
| | - Ksenia Wróblewska
- National Research Institute of Animal Production, Animal Molecular Biology, 31-047 Cracow, Poland; (K.Z.); (K.W.)
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Ghorbani A, Hosseinie F, Khorshid Sokhangouy S, Islampanah M, Khojasteh-Leylakoohi F, Maftooh M, Nassiri M, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Nazari E, Avan A. The prognostic, diagnostic, and therapeutic impact of Long noncoding RNAs in gastric cancer. Cancer Genet 2024; 282-283:14-26. [PMID: 38157692 DOI: 10.1016/j.cancergen.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 11/27/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
Gastric cancer (GC), ranking as the third deadliest cancer globally, faces challenges of late diagnosis and limited treatment efficacy. Long non-coding RNAs (lncRNAs) emerge as valuable treasured targets for cancer prognosis, diagnosis, and therapy, given their high specificity, convenient non-invasive detection in body fluids, and crucial roles in diverse physiological and pathological processes. Research indicates the significant involvement of lncRNAs in various aspects of GC pathogenesis, including initiation, metastasis, and recurrence, underscoring their potential as novel diagnostic and prognostic biomarkers, as well as therapeutic targets for GC. Despite existing challenges in the clinical application of lncRNAs in GC, the evolving landscape of lncRNA molecular biology holds promise for advancing the survival and treatment outcomes of gastric cancer patients. This review provides insights into recent studies on lncRNAs in gastric cancer, elucidating their molecular mechanisms and exploring the potential clinical applications in GC.
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Affiliation(s)
- Atousa Ghorbani
- Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Hosseinie
- Department of Nursing, Faculty of Nursing and Midwifery, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Saeideh Khorshid Sokhangouy
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Muhammad Islampanah
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Nassiri
- Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Nazari
- Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Imran M, Abida, Eltaib L, Siddique MI, Kamal M, Asdaq SMB, Singla N, Al-Hajeili M, Alhakami FA, AlQarni AF, Abdulkhaliq AA, Rabaan AA. Beyond the genome: MALAT1's role in advancing urologic cancer care. Pathol Res Pract 2024; 256:155226. [PMID: 38452585 DOI: 10.1016/j.prp.2024.155226] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 03/09/2024]
Abstract
Urologic cancers (UCs), which include bladder, kidney, and prostate tumors, account for almost a quarter of all malignancies. Long non-coding RNAs (lncRNAs) are tissue-specific RNAs that influence cell growth, death, and division. LncRNAs are dysregulated in UCs, and their abnormal expression may allow them to be used in cancer detection, outlook, and therapy. With the identification of several novel lncRNAs and significant exploration of their functions in various illnesses, particularly cancer, the study of lncRNAs has evolved into a new obsession. MALAT1 is a flexible tumor regulator implicated in an array of biological activities and disorders, resulting in an important research issue. MALAT1 appears as a hotspot, having been linked to the dysregulation of cell communication, and is intimately linked to cancer genesis, advancement, and response to treatment. MALAT1 additionally operates as a competitive endogenous RNA, binding to microRNAs and resuming downstream mRNA transcription and operation. This regulatory system influences cell growth, apoptosis, motility, penetration, and cell cycle pausing. MALAT1's evaluation and prognosis significance are highlighted, with a thorough review of its manifestation levels in several UC situations and its association with clinicopathological markers. The investigation highlights MALAT1's adaptability as a possible treatment target, providing fresh ways for therapy in UCs as we integrate existing information The article not only gathers current knowledge on MALAT1's activities but also lays the groundwork for revolutionary advances in the treatment of UCs.
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Affiliation(s)
- Mohd Imran
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
| | - Abida
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Lina Eltaib
- Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Muhammad Irfan Siddique
- Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia
| | - Mehnaz Kamal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | | | - Neelam Singla
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur 302017, India
| | - Marwan Al-Hajeili
- Department of Medicine, King Abdulaziz University, Jeddah 23624, Saudi Arabia
| | - Fatemah Abdulaziz Alhakami
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Saudi Arabia
| | - Ahmed Farhan AlQarni
- Histopathology Laboratory, Najran Armed Forces Hospital, Najran 66251, Saudi Arabia
| | - Altaf A Abdulkhaliq
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan
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Peng L, Yang Y, Yang C, Li Z, Cheong N. HRGCNLDA: Forecasting of lncRNA-disease association based on hierarchical refinement graph convolutional neural network. MATHEMATICAL BIOSCIENCES AND ENGINEERING : MBE 2024; 21:4814-4834. [PMID: 38872515 DOI: 10.3934/mbe.2024212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
Long non-coding RNA (lncRNA) is considered to be a crucial regulator involved in various human biological processes, including the regulation of tumor immune checkpoint proteins. It has great potential as both a cancer biomolecular biomarker and therapeutic target. Nevertheless, conventional biological experimental techniques are both resource-intensive and laborious, making it essential to develop an accurate and efficient computational method to facilitate the discovery of potential links between lncRNAs and diseases. In this study, we proposed HRGCNLDA, a computational approach utilizing hierarchical refinement of graph convolutional neural networks for forecasting lncRNA-disease potential associations. This approach effectively addresses the over-smoothing problem that arises from stacking multiple layers of graph convolutional neural networks. Specifically, HRGCNLDA enhances the layer representation during message propagation and node updates, thereby amplifying the contribution of hidden layers that resemble the ego layer while reducing discrepancies. The results of the experiments showed that HRGCNLDA achieved the highest AUC-ROC (area under the receiver operating characteristic curve, AUC for short) and AUC-PR (area under the precision versus recall curve, AUPR for short) values compared to other methods. Finally, to further demonstrate the reliability and efficacy of our approach, we performed case studies on the case of three prevalent human diseases, namely, breast cancer, lung cancer and gastric cancer.
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Affiliation(s)
- Li Peng
- College of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan 411201, China
- Hunan Key Laboratory for Service Computing and Novel Software Technology, Hunan University of Science and Technology, Xiangtan 411201, China
| | - Yujie Yang
- College of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan 411201, China
| | - Cheng Yang
- College of Computer Science and Engineering, Hunan University of Science and Technology, Xiangtan 411201, China
| | - Zejun Li
- School of Computer Science and Engineering, Hunan Institute of Technology, Hengyang 421002, China
| | - Ngai Cheong
- Faculty of Applied Sciences, Macao Polytechnic University, Macau 999078, China
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12
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Kong X, Patel NA, Chalfant CE, Cooper DR. Ceramide synthesis regulates biogenesis and packaging of exosomal MALAT1 from adipose derived stem cells, increases dermal fibroblast migration and mitochondrial function. Cell Commun Signal 2023; 21:221. [PMID: 37620957 PMCID: PMC10463839 DOI: 10.1186/s12964-022-00900-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 05/17/2022] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND The function of exosomes, small extracellular vesicles (sEV) secreted from human adipose-derived stem cells (ADSC), is becoming increasingly recognized as a means of transferring the regenerative power of stem cells to injured cells in wound healing. Exosomes are rich in ceramides and long noncoding RNA (lncRNA) like metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). We identified putative ceramide responsive cis-elements (CRCE) in MALAT1. We hypothesized that CRCE respond to cellular ceramide levels to regulate sEV MALAT1 packaging. MALAT1 levels by many cells exceed those of protein coding genes and it's expression is equally high in exosomes. Ceramide also regulates exosome synthesis, however, the contents of exosome cargo via sphingomyelinase and ceramide synthase pathways has not been demonstrated. METHODS ADSC were treated with an inhibitor of sphingomyelinase, GW4869, and stimulators of ceramide synthesis, C2- and C6-short chain ceramides, prior to collection of conditioned media (CM). sEV were isolated from CM, and then used to treat human dermal fibroblast (HDF) cultures in cell migration scratch assays, and mitochondrial stress tests to evaluate oxygen consumption rates (OCR). RESULTS Inhibition of sphingomyelinase by treatment of ADSC with GW4869 lowered levels of MALAT1 in small EVs. Stimulation of ceramide synthesis using C2- and C6- ceramides increased cellular, EVs levels of MALAT1. The functional role of sEV MALAT1 was evaluated in HDF by applying EVs to HDF. Control sEV increased migration of HDF, and significantly increased ATP production, basal and maximal respiration OCR. sEV from GW4869-treated ADSC inhibited cell migration and maximal respiration. However, sEV from C2- and C6-treated cells, respectively, increased both functions but not significantly above control EV except for maximal respiration. sEV were exosomes except when ADSC were treated with GW4869 and C6-ceramide, then they were larger and considered microvesicles. CONCLUSIONS Ceramide synthesis regulates MALAT1 EV content. Sphingomyelinase inhibition blocked MALAT1 from being secreted from ADSC EVs. Our report is consistent with those of MALAT1 increasing cell migration and mitochondrial MALAT1 altering maximal respiration in cells. Since MALAT1 is important for exosome function, it stands that increased exosomal MALAT1 should be beneficial for wound healing as shown with these assays. Video Abstract.
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Affiliation(s)
- Xaioyuan Kong
- Department of Veterans Affairs, J.A. Haley Veterans Hospital, Research Service 151, Tampa, Fl 33711 USA
| | - Niketa A. Patel
- Department of Veterans Affairs, J.A. Haley Veterans Hospital, Research Service 151, Tampa, Fl 33711 USA
- Department of Molecular Medicine, Morsani College of Medicine, Tampa, USA
| | - Charles E. Chalfant
- Department of Veterans Affairs, J.A. Haley Veterans Hospital, Research Service 151, Tampa, Fl 33711 USA
- Department of Cellular Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33612 USA
| | - Denise R. Cooper
- Department of Veterans Affairs, J.A. Haley Veterans Hospital, Research Service 151, Tampa, Fl 33711 USA
- Department of Molecular Medicine, Morsani College of Medicine, Tampa, USA
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13
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Silva JMC, Teixeira EB, Mourão RMDS, Ferraz RS, Moreira FC, de Assumpção PP, Calcagno DQ. The landscape of lncRNAs in gastric cancer: from molecular mechanisms to potential clinical applications. Front Pharmacol 2023; 14:1237723. [PMID: 37670949 PMCID: PMC10476871 DOI: 10.3389/fphar.2023.1237723] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 08/04/2023] [Indexed: 09/07/2023] Open
Abstract
Gastric cancer (GC) is a highly prevalent and deadly malignant neoplasm worldwide. Currently, long non-coding RNAs (lncRNAs) have recently been identified as crucial regulators implicated in GC development and progression. Dysregulated expression of lncRNAs is commonly associated with enhanced tumor migration, invasiveness, and therapy resistance, highlighting their potential as promising targets for clinical applications. This review offers a comprehensive historical overview of lncRNAs in GC, describes the molecular mechanisms, and discusses the prospects and challenges of establishing lncRNAs as precision biomarkers.
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Affiliation(s)
| | | | | | - Rafaella Sousa Ferraz
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belem, Pará, Brazil
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14
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Lu X, Li Y, Li Y, Zhang X, Shi J, Feng H, Gao Y, Yu Z. Advances of multi-omics applications in hepatic precancerous lesions and hepatocellular carcinoma: The role of extracellular vesicles. Front Mol Biosci 2023; 10:1114594. [PMID: 37006626 PMCID: PMC10060991 DOI: 10.3389/fmolb.2023.1114594] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
Due to the lack of distinct early symptoms and specific biomarkers, most patients with hepatocellular carcinoma (HCC) are usually diagnosed at advanced stages, rendering the treatment ineffective and useless. Therefore, recognition of the malady at precancerous lesions and early stages is particularly important for improving patient outcomes. The interest in extracellular vesicles (EVs) has been growing in recent years with the accumulating knowledge of their multiple cargoes and related multipotent roles in the modulation of immune response and tumor progression. By virtue of the rapid advancement of high-throughput techniques, multiple omics, including genomics/transcriptomics, proteomics, and metabolomics/lipidomics, have been widely integrated to analyze the role of EVs. Comprehensive analysis of multi-omics data will provide useful insights for discovery of new biomarkers and identification of therapeutic targets. Here, we review the attainment of multi-omics analysis to the finding of the potential role of EVs in early diagnosis and the immunotherapy in HCC.
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Affiliation(s)
- Xiaona Lu
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuyao Li
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yue Li
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xuemei Zhang
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jia Shi
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hai Feng
- Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Hai Feng, ; Yueqiu Gao, ; Zhuo Yu,
| | - Yueqiu Gao
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Hai Feng, ; Yueqiu Gao, ; Zhuo Yu,
| | - Zhuo Yu
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Hai Feng, ; Yueqiu Gao, ; Zhuo Yu,
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15
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Loe AKH, Zhu L, Kim TH. Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesis. Exp Mol Med 2023; 55:22-31. [PMID: 36653445 PMCID: PMC9898530 DOI: 10.1038/s12276-023-00926-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 11/08/2022] [Accepted: 11/22/2022] [Indexed: 01/20/2023] Open
Abstract
Gastric cancer (GC) is one of the most common and deadly cancers in the world. It is a multifactorial disease highly influenced by environmental factors, which include radiation, smoking, diet, and infectious pathogens. Accumulating evidence suggests that epigenetic regulators are frequently altered in GC, playing critical roles in gastric tumorigenesis. Epigenetic regulation involves DNA methylation, histone modification, and noncoding RNAs. While it is known that environmental factors cause widespread alterations in DNA methylation, promoting carcinogenesis, the chromatin- and noncoding RNA-mediated mechanisms of gastric tumorigenesis are still poorly understood. In this review, we focus on discussing recent discoveries addressing the roles of histone modifiers and noncoding RNAs and the mechanisms of their interactions in gastric tumorigenesis. A better understanding of epigenetic regulation would likely facilitate the development of novel therapeutic approaches targeting specific epigenetic regulators in GC.
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Affiliation(s)
- Adrian Kwan Ho Loe
- grid.42327.300000 0004 0473 9646Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4 Canada ,grid.17063.330000 0001 2157 2938Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8 Canada
| | - Lexin Zhu
- grid.42327.300000 0004 0473 9646Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4 Canada ,grid.17063.330000 0001 2157 2938Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8 Canada
| | - Tae-Hee Kim
- Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada. .,Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
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16
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Shen W, Yu Q, Pu Y, Xing C. Upregulation of Long Noncoding RNA MALAT1 in Colorectal Cancer Promotes Radioresistance and Aggressive Malignance. Int J Gen Med 2022; 15:8365-8380. [PMID: 36465270 PMCID: PMC9717691 DOI: 10.2147/ijgm.s393270] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/18/2022] [Indexed: 09/07/2023] Open
Abstract
Background Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a conserved transcript with 8000 nt, is highly associated with malignancy of numerous cancer types. However, the function of MALAT1 plays in regulating the response to radiotherapy in colorectal cancer (CRC) remains unclear. Thus, the object of this study is to investigate the functions of MALAT1 in CRC radioresistance. Methods First, the expression of MALAT1 in colon adenocarcinoma (COAD) was analyzed through the Cancer Genome Atlas (TCGA) database. Then, we detected the expression level of MALAT1 in tumor tissues and CRC cell lines and analyzed the relevance of MALAT1 and clinicopathological parameters. In the end, the effect of silencing MALAT1 on the radiosensitivity of CRC cells was investigated, and its potential mechanism was preliminarily illustrated. Results The analysis of TCGA data showed that MALAT1 was closely related to the type of tumor, and high expression of MALAT1 was remarkably relevant to poor outcome. MALAT1 was highly expressed in CRC tissues and cell lines and related to tumor stages. Knockdown of MALAT1 could significantly suppress colony survival, proliferation, and migration and increase apoptosis, G2/M phase arrest, and formation of gamma-H2AX foci in HCT116, whether in combination with X-rays or not. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that the regulated proteins were principally enriched in the glycosaminoglycan degradation pathway after silencing MALAT1. Conclusion Our results implied that MALAT1 was highly expressed in CRC and associated with tumor stage and prognosis. Silencing MALAT1 can increase HCT116 cell radiosensitivity, which may be potentially influenced by glycosaminoglycan degradation pathway.
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Affiliation(s)
- Wenqi Shen
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Qifeng Yu
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Yuwei Pu
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Chungen Xing
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
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17
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Najafi S, Khatami SH, Khorsand M, Jamali Z, Shabaninejad Z, Moazamfard M, Majidpoor J, Aghaei Zarch SM, Movahedpour A. Long non-coding RNAs (lncRNAs); roles in tumorigenesis and potentials as biomarkers in cancer diagnosis. Exp Cell Res 2022; 418:113294. [PMID: 35870535 DOI: 10.1016/j.yexcr.2022.113294] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/11/2022] [Accepted: 07/16/2022] [Indexed: 12/15/2022]
Abstract
New research has indicated that long non-coding RNAs (lncRNAs) play critical roles in a broad range of biological processes, including the pathogenesis of many complex human diseases, including cancer. The detailed regulation mechanisms of many lncRNAs in cancer initiation and progression have yet to be discovered, even though a few of lncRNAs' functions in cancer have been characterized. In the present study, we summarize recent advances in the mechanisms and functions of lncRNAs in cancer. We focused on the roles of newly-identified lncRNAs as oncogenes and tumor suppressors, as well as the potential pathways these molecules could play. The paper also discusses their potential uses as biomarkers for the diagnosis and prognosis of cancer.
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Affiliation(s)
- Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Seyyed Hossein Khatami
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marjan Khorsand
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zeinab Jamali
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Shabaninejad
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Jamal Majidpoor
- Department of Anatomy, Faculty of Medicine, Infectious Disease Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Seyed Mohsen Aghaei Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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18
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Yang X, Qin C, Zhao B, Li T, Wang Y, Li Z, Li T, Wang W. Long Noncoding RNA and Circular RNA: Two Rising Stars in Regulating Epithelial-Mesenchymal Transition of Pancreatic Cancer. Front Oncol 2022; 12:910678. [PMID: 35719940 PMCID: PMC9204003 DOI: 10.3389/fonc.2022.910678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/09/2022] [Indexed: 11/13/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with especially poor prognosis. However, the molecular mechanisms of pancreatic oncogenesis and malignant progression are not fully elucidated. Epithelial-mesenchymal transition (EMT) process is important to drive pancreatic carcinogenesis. Recently, long noncoding RNAs (lncRNAs) and circular RNAs(circRNAs) have been characterized to participate in EMT in PDAC, which can affect the migration and invasion of tumor cells by playing important roles in epigenetic processes, transcription, and post-transcriptional regulation. LncRNAs can act as competing endogenous RNAs (ceRNA) to sequester target microRNAs(miRNAs), bind to the genes which localize physically nearby, and directly interact with EMT-related proteins. Currently known circRNAs mostly regulate the EMT process in PDAC also by acting as a miRNA sponge, directly affecting the protein degradation process. Therefore, exploring the functions of lncRNAs and circRNAs in EMT during pancreatic cancer might help pancreatic cancer treatments.
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Affiliation(s)
- Xiaoying Yang
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Cheng Qin
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bangbo Zhao
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tianhao Li
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuanyang Wang
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zeru Li
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tianyu Li
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weibin Wang
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Roshani M, Jafari A, Loghman A, Sheida AH, Taghavi T, Tamehri Zadeh SS, Hamblin MR, Homayounfal M, Mirzaei H. Applications of resveratrol in the treatment of gastrointestinal cancer. Biomed Pharmacother 2022; 153:113274. [PMID: 35724505 DOI: 10.1016/j.biopha.2022.113274] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/28/2022] [Accepted: 06/08/2022] [Indexed: 12/15/2022] Open
Abstract
Natural product compounds have lately attracted interest in the scientific community as a possible treatment for gastrointestinal (GI) cancer, due to their anti-inflammatory and anticancer properties. There are many preclinical, clinical, and epidemiological studies, suggesting that the consumption of polyphenol compounds, which are abundant in vegetables, grains, fruits, and pulses, may help to prevent various illnesses and disorders from developing, including several GI cancers. The development of GI malignancies follows a well-known path, in which normal gastrointestinal cells acquire abnormalities in their genetic composition, causing the cells to continuously proliferate, and metastasize to other sites, especially the brain and liver. Natural compounds with the ability to affect oncogenic pathways might be possible treatments for GI malignancies, and could easily be tested in clinical trials. Resveratrol is a non-flavonoid polyphenol and a natural stilbene, acting as a phytoestrogen with anti-cancer, cardioprotective, anti-oxidant, and anti-inflammatory properties. Resveratrol has been shown to overcome resistance mechanisms in cancer cells, and when combined with conventional anticancer drugs, could sensitize cancer cells to chemotherapy. Several new resveratrol analogs and nanostructured delivery vehicles with improved anti-GI cancer efficacy, absorption, and pharmacokinetic profiles have already been developed. This present review focuses on the in vitro and in vivo effects of resveratrol on GI cancers, as well as the underlying molecular mechanisms of action.
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Affiliation(s)
- Mohammad Roshani
- Internal Medicine and Gastroenterology, Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ameneh Jafari
- Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran; Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Amir Hossein Sheida
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | | | | | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
| | - Mina Homayounfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, 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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Li J, Chen S, Pan X, Yuan Y, Shen HB. Cell clustering for spatial transcriptomics data with graph neural networks. NATURE COMPUTATIONAL SCIENCE 2022; 2:399-408. [PMID: 38177586 DOI: 10.1038/s43588-022-00266-5] [Citation(s) in RCA: 75] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 05/19/2022] [Indexed: 01/06/2024]
Abstract
Spatial transcriptomics data can provide high-throughput gene expression profiling and the spatial structure of tissues simultaneously. Most studies have relied on only the gene expression information but cannot utilize the spatial information efficiently. Taking advantage of spatial transcriptomics and graph neural networks, we introduce cell clustering for spatial transcriptomics data with graph neural networks, an unsupervised cell clustering method based on graph convolutional networks to improve ab initio cell clustering and discovery of cell subtypes based on curated cell category annotation. On the basis of its application to five in vitro and in vivo spatial datasets, we show that cell clustering for spatial transcriptomics outperforms other spatial clustering approaches on spatial transcriptomics datasets and can clearly identify all four cell cycle phases from multiplexed error-robust fluorescence in situ hybridization data of cultured cells. From enhanced sequential fluorescence in situ hybridization data of brain, cell clustering for spatial transcriptomics finds functional cell subtypes with different micro-environments, which are all validated experimentally, inspiring biological hypotheses about the underlying interactions among the cell state, cell type and micro-environment.
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Affiliation(s)
- Jiachen Li
- Institute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai, China
| | - Siheng Chen
- Cooperative Medianet Innovation Center (CMIC), Shanghai Jiao Tong University, Shanghai, China
- Shanghai Artificial Intelligence Laboratory, Shanghai, China
| | - Xiaoyong Pan
- Institute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai, China
| | - Ye Yuan
- Institute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, Shanghai, China.
- Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai, China.
| | - Hong-Bin Shen
- Institute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, Shanghai, China.
- Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai, China.
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21
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Liu XY, Zhang TQ, Zhang Q, Guo J, Zhang P, Mao T, Tian ZB, Zhang CP, Li XY. Differential Long Non-Coding RNA Expression Analysis in Chronic Non-Atrophic Gastritis, Gastric Mucosal Intraepithelial Neoplasia, and Gastric Cancer Tissues. Front Genet 2022; 13:833857. [PMID: 35571069 PMCID: PMC9091194 DOI: 10.3389/fgene.2022.833857] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Accepted: 03/25/2022] [Indexed: 11/13/2022] Open
Abstract
Gastric cancer (GC) has a high incidence worldwide, and when detected, the majority of patients have already progressed to advanced stages. Long non-coding RNAs (lncRNAs) have a wide range of biological functions and affect tumor occurrence and development. However, the potential role of lncRNAs in GC diagnosis remains unclear. We selected five high-quality samples from each group of chronic non-atrophic gastritis, gastric mucosal intraepithelial neoplasia, and GC tissues for analysis. RNA-seq was used to screen the differentially expressed lncRNAs, and we identified 666 differentially expressed lncRNAs between the chronic non-atrophic gastritis and GC groups, 13 differentially expressed lncRNAs between the gastric mucosal intraepithelial neoplasia and GC groups, and 507 differentially expressed lncRNAs between the chronic non-atrophic gastritis and gastric mucosal intraepithelial neoplasia groups. We also identified six lncRNAs (lncRNA H19, LINC00895, lnc-SRGAP2C-16, lnc-HLA-C-2, lnc-APOC1-1, and lnc-B3GALT2-1) which not only differentially expressed between the chronic non-atrophic gastritis and GC groups, but also differentially expressed between the gastric mucosal intraepithelial neoplasia and GC groups. Furthermore, RT-qPCR was used to verify the differentially co-expressed lncRNAs. LncSEA was used to conduct a functional analysis of differentially expressed lncRNAs. We also predicted the target mRNAs of the differentially expressed lncRNAs through bioinformatics analysis and analyzed targeting correlations between three differentially co-expressed lncRNAs and mRNAs (lncRNA H19, LINC00895, and lnc-SRGAP2C-16). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to explore the functions of target mRNAs of differentially expressed lncRNAs. In conclusion, our study provides a novel perspective on the potential functions of differentially expressed lncRNAs in GC occurrence and development, indicating that the differentially expressed lncRNAs might be new biomarkers for early GC diagnosis.
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Affiliation(s)
- Xin-Yuan Liu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Tian-Qi Zhang
- Department of Gastroenterology, Qingdao Women and Children’s Hospital, Qingdao, China
| | - Qi Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jing Guo
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Peng Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Tao Mao
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zi-Bin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Cui-Ping Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao-Yu Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
- *Correspondence: Xiao-Yu Li,
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22
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Zhang S, Yang X, Zhang Z, Xiong Y, Zhang Y, Li C, Liu O, Wang X, Peng Y. Expression patterns of long non-coding RNAs in peripheral blood mononuclear cells of non-segmental vitiligo. Medicine (Baltimore) 2021; 100:e28399. [PMID: 34941177 PMCID: PMC8702240 DOI: 10.1097/md.0000000000028399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 12/02/2021] [Accepted: 12/02/2021] [Indexed: 11/07/2022] Open
Abstract
OBJECTIVE We explored the patterns of long non-coding RNA (lncRNA) expression in peripheral blood mononuclear cells (PBMCs) from patients with non-segmental vitiligo. METHODS We used high-throughput RNA sequencing technology to generate sequence data from five patients with non-segmental vitiligo alongside five normal healthy individuals, and then performed bioinformatics analyses to detect the differential expression of lncRNA in PBMCs. Gene Ontology (GO) and pathway analyses were performed for functional annotation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify gene expression. Target miRNAs and mRNAs of differentially expressed lncRNAs were predicted using bioinformatics analysis. RESULTS A total of 292 lncRNAs were differentially expressed in non-segmental vitiligo (fold change ≥ 2.0, P < .05), of which 171 were upregulated and 121 were downregulated. Six differentially expressed lncRNAs were selected, namely ENST00000460164.1, ENST00000393264.2, NR-046211.1, NR-135491.1, NR-135320.1, and ENST00000381108.3, for validation by qRT-PCR. The results showed that ENST00000460164.1 and NR-046211.1 were highly expressed in PBMCs of non-segmental vitiligo. An lncRNA-miRNA-mRNA network containing two lncRNAs, 17 miRNAs, and 223 mRNAs was constructed. CONCLUSION Our results revealed patterns of differentially expressed lncRNAs in the PBMCs of non-segmental vitiligo individuals. ENST00000460164.1, and NR-046211.1 may be potential biomarkers and drug targets for the treatment of non-segmental vitiligo.
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Affiliation(s)
- Shulan Zhang
- Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xinyue Yang
- Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhibin Zhang
- Department of Dermatology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yifeng Xiong
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yingpeng Zhang
- Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Chunming Li
- Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ougen Liu
- Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xiaoyan Wang
- Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yating Peng
- Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Zhou Q, Liu L, Zhou J, Chen Y, Xie D, Yao Y, Cui D. Novel Insights Into MALAT1 Function as a MicroRNA Sponge in NSCLC. Front Oncol 2021; 11:758653. [PMID: 34778078 PMCID: PMC8578859 DOI: 10.3389/fonc.2021.758653] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 10/06/2021] [Indexed: 12/21/2022] Open
Abstract
The long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was initially found to be overexpressed in early non-small cell lung cancer (NSCLC). Accumulating studies have shown that MALAT1 is overexpressed in the tissue or serum of NSCLC and plays a key role in its occurrence and development. In addition, the expression level of MALAT1 is significantly related to the tumor size, stage, metastasis, and distant invasion of NSCLC. Therefore, MALAT1 could be used as a biomarker for the early diagnosis, severity assessment, or prognosis evaluation of NSCLC patients. This review describes the basic properties and biological functions of MALAT1, focuses on the specific molecular mechanism of MALAT1 as a microRNA sponge in the occurrence and development of NSCLC in recent years, and emphasizes the application and potential prospect of MALAT1 in molecular biological markers and targeted therapy of NSCLC.
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Affiliation(s)
- Qinfeng Zhou
- Department of Laboratory Medicine, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China
| | - Lianfang Liu
- Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China
| | - Jing Zhou
- Department of Laboratory Medicine, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China
| | - Yuanyuan Chen
- Department of Laboratory Medicine, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China
| | - Dacheng Xie
- Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
| | - Yinan Yao
- Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dawei Cui
- Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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24
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Hu D, Lou X, Meng N, Li Z, Teng Y, Zou Y, Wang F. Peripheral Blood-Based DNA Methylation of Long Non-Coding RNA H19 and Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promoters are Potential Non-Invasive Biomarkers for Gastric Cancer Detection. Cancer Control 2021; 28:10732748211043667. [PMID: 34615385 PMCID: PMC8504648 DOI: 10.1177/10732748211043667] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Introduction The early diagnosis and detection could greatly improve the clinical outcome of gastric cancer (GC) patients. However, the non-invasive biomarkers for GC detection remain to be identified. Method We used online databases (GEPIA, UALCAN, Kaplan-Meier plotter, TIMER, and MEXPRESS) to explore the association between H19 or metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in tissues and the occurrence, development, prognosis, the levels of immune cell infiltration, and methylation of GC; the correlation between mRNA expression and DNA methylation levels of genes were also examined. Methylation levels of H19 or MALAT1 in peripheral blood were compared between 150 GC patients and 100 healthy controls (HCs). Predictive nomograms were constructed among female and male groups for GC diagnosis. The calibration curves, Hosmer–Lemeshow test, and decision curve analysis were also used to examine the nomograms’ predictive ability and clinical values. Results Using multiple online databases, we found that the mRNA expressions of H19 and MALAT1 in tissues were related to the occurrence of GC, and such expressions were associated with immune cell infiltration of GC and negatively correlated with DNA methylation levels of H19 and MALAT1. H19 gene, H19C island, and MALAT1B island, as well as 20 CpG sites were hypermethylated in peripheral blood of GC patients compared with HCs; similar results were also found in female and male groups (P < .05 for all). The combination of H19c3, H19c4, MALAT1b12, and age, as well as the combination of H19b7, H19c1, H19c5, and age in the nomograms could distinguish GC patients from HCs in the female group and male group, respectively. Conclusion We found statistically significant hypermethylation of H19 and MALAT1 promoters in GC patients, and meaningful sensitivity and specificity of MALAT1 and H19 methylation in discriminating GC and HCs were observed in both female and male groups, which indicates that the peripheral blood-based DNA methylation of H19 and MALAT1 could act as potential non-invasive biomarkers for the diagnosis of GC.
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Affiliation(s)
- Dingtao Hu
- Department of Oncology, 36639The First Affiliated Hospital of Anhui Medical University, China
| | - Xiaoqi Lou
- Department of Oncology, 36639The First Affiliated Hospital of Anhui Medical University, China
| | - Nana Meng
- Department of Quality Management Office, 533251The Second Affiliated Hospital of Anhui Medical University, China
| | - Zhen Li
- Department of Epidemiology and Biostatistics, School of Public Health of Anhui Medical University, China
| | - Ying Teng
- Department of Epidemiology and Biostatistics, School of Public Health of Anhui Medical University, China
| | - Yanfeng Zou
- Department of Epidemiology and Biostatistics, School of Public Health of Anhui Medical University, China
| | - Fang Wang
- Department of Oncology, 36639The First Affiliated Hospital of Anhui Medical University, China
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25
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Animesh S, Choudhary R, Wong BJH, Koh CTJ, Ng XY, Tay JKX, Chong WQ, Jian H, Chen L, Goh BC, Fullwood MJ. Profiling of 3D Genome Organization in Nasopharyngeal Cancer Needle Biopsy Patient Samples by a Modified Hi-C Approach. Front Genet 2021; 12:673530. [PMID: 34539729 PMCID: PMC8446523 DOI: 10.3389/fgene.2021.673530] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 07/31/2021] [Indexed: 11/16/2022] Open
Abstract
Nasopharyngeal cancer (NPC), a cancer derived from epithelial cells in the nasopharynx, is a cancer common in China, Southeast Asia, and Africa. The three-dimensional (3D) genome organization of nasopharyngeal cancer is poorly understood. A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method for the characterization of chromatin interactions in solid cancer needle biopsy samples. Here, we developed Biop-C, a modified in situ Hi-C method using solid cancer needle biopsy samples. We applied Biop-C to characterize three nasopharyngeal cancer solid cancer needle biopsy patient samples. We identified topologically associated domains (TADs), chromatin interaction loops, and frequently interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from the Biop-C heatmaps. We observed that the genomic features are shared at some important oncogenes, but the patients also display extensive heterogeneity at certain genomic loci. On analyzing the super enhancer landscape in nasopharyngeal cancer cell lines, we found that the super enhancers are associated with FIREs and can be linked to distal genes via chromatin loops in NPC. Taken together, our results demonstrate the utility of our Biop-C method in investigating 3D genome organization in solid cancers.
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Affiliation(s)
- Sambhavi Animesh
- Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore, Singapore
| | - Ruchi Choudhary
- Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore, Singapore.,School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | | | - Charlotte Tze Jia Koh
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | - Xin Yi Ng
- Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore
| | - Joshua Kai Xun Tay
- Department of Otolaryngology - Head and Neck Surgery, National University of Singapore, Singapore, Singapore
| | - Wan-Qin Chong
- Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore
| | - Han Jian
- Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore, Singapore
| | - Leilei Chen
- Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore, Singapore.,Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Boon Cher Goh
- Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore, Singapore.,Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore.,Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore
| | - Melissa Jane Fullwood
- Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore, Singapore.,School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
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26
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Qian Z, Chen L, Wang X, Kan Y, Wang Y, Yu Y, Wang X, Zhao Z, Yang H, Ge P, Ding T, Zhai Q, Zhao H. Increased MALAT1 expression predicts poor prognosis in primary gastrointestinal diffuse large B-cell lymphoma. Clin Exp Med 2021; 22:183-191. [PMID: 34427833 DOI: 10.1007/s10238-021-00748-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 07/22/2021] [Indexed: 11/24/2022]
Abstract
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the pathogenesis and progression of several cancers. However, the potential effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in patients with PGI-DLBCL. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably upregulated in PGI-DLBCL tissues compared to paired adjacent non-tumor tissues (P < 0.001), and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB), advanced stage (stages IIE-IV) and International Prognostic Index (IPI) score (3-5) groups (P = 0.01, P < 0.001 and P < 0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression correlated with inferior overall survival (OS) and progression-free survival in PGI-DLBCL patients (P < 0.001 and P < 0.001, respectively), and our multivariate analysis results suggested that upregulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors for PGI-DLBCL. In conclusion, our results demonstrate that MALAT1 may serve as a novel prognostic biomarker and an ideal therapeutic target for patients with PGI-DLBCL.
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Affiliation(s)
- Zhengzi Qian
- Key Laboratory of Cancer Prevention and Therapy, Department of Lymphoma, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Leiyuan Chen
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Xinyuan Wang
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Yutian Kan
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Yafei Wang
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Yong Yu
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Xiaofang Wang
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Zhigang Zhao
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Hongliang Yang
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China
| | - Peng Ge
- Key Laboratory of Cancer Prevention and Therapy, Department of Laboratory, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Tingting Ding
- Key Laboratory of Cancer Prevention and Therapy, Department of Pathology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Qiongli Zhai
- Key Laboratory of Cancer Prevention and Therapy, Department of Pathology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Haifeng Zhao
- Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
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27
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Kim SS, Baek GO, Son JA, Ahn HR, Yoon MK, Cho HJ, Yoon JH, Nam SW, Cheong JY, Eun JW. Early detection of hepatocellular carcinoma via liquid biopsy: panel of small extracellular vesicle-derived long noncoding RNAs identified as markers. Mol Oncol 2021; 15:2715-2731. [PMID: 34185961 PMCID: PMC8486572 DOI: 10.1002/1878-0261.13049] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 06/08/2021] [Accepted: 06/28/2021] [Indexed: 12/25/2022] Open
Abstract
This study investigated the diagnostic potential of serum small extracellular vesicle‐derived long noncoding RNAs (EV‐lncRNAs) for hepatocellular carcinoma (HCC). Driver oncogenic lncRNA candidates were selected by a comparative analysis of lncRNA expression profiles from two whole transcriptome human HCC datasets (Catholic_LIHC and TCGA_LIHC). Expression of selected lncRNAs in serum and small EVs was evaluated using quantitative reverse transcription PCR. Diagnostic power of serum EV‐lncRNAs for HCC was determined in the test (n = 44) and validation (n = 139) cohorts. Of the six promising driver onco‐lncRNAs, DLEU2, HOTTIP, MALAT1, and SNHG1 exhibited favorable performance in the test cohort. In the validation cohort, serum EV‐MALAT1 displayed excellent discriminant ability, while EV‐DLEU2, EV‐HOTTIP, and EV‐SNHG1 showed good discriminant ability between HCC and non‐HCC. Furthermore, a panel combining EV‐MALAT1 and EV‐SNHG1 achieved the best area under the curve (AUC; 0.899, 95% CI = 0.816–0.982) for very early HCC, whereas a panel with EV‐DLEU2 and alpha‐fetoprotein exhibited the best positivity (96%) in very early HCC. Serum small EV‐MALAT1, EV‐DLEU2, EV‐HOTTIP, and EV‐SNHG1 may represent promising diagnostic markers for very early‐stage HCC.
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Affiliation(s)
- Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Geum Ok Baek
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Ju A Son
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.,Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
| | - Hye Ri Ahn
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.,Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea
| | - Moon Kyung Yoon
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Hyo Jung Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Jung Hwan Yoon
- Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Suk Woo Nam
- Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea.,Functional RNomics Research Center, The Catholic University of Korea, Seoul, Korea.,Department of Biomedicine & Health Sciences, Graduate School of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Jung Woo Eun
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
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28
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De Martino M, Esposito F, Pallante P. Long non-coding RNAs regulating multiple proliferative pathways in cancer cell. Transl Cancer Res 2021; 10:3140-3157. [PMID: 35116622 PMCID: PMC8797882 DOI: 10.21037/tcr-21-230] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/27/2021] [Indexed: 01/17/2023]
Abstract
Long non-coding RNAs (lncRNAs) belong to an extremely heterogeneous class of non-coding RNAs with a length ranging from 200 to 100,000 bp. They modulate a series of cellular pathways in both physiological and pathological context. It is no coincidence that they are expressed in an aberrant way in pathologies such as cancer, so as to deserve to be subclassified as oncogenes or tumor suppressors. These molecules are also involved in the regulation of cancer cell proliferation. Several lncRNAs are able to modulate cell growth both positively and negatively, and in this review we have focused on a small group of them, characterized by the simultaneous action on different pathways regulating cell proliferation. They have been considered in the light of their behavior in three different subtypes of proliferative pathways that we can define as (I) tumor suppressor, (II) oncogenic and (III) transcriptionally-driven. More specifically, we have characterized some lncRNAs considered oncogenes (such as H19, linc-ROR, MALAT1, HULC, HOTAIR and ANRIL), tumor suppressors (such as MEG3 and lincRNA-p21), and both oncogenes/tumor suppressors (UCA1 and TUG1) in a little more detail. As can be understood from the review, the interactions between lncRNAs and their molecular targets, only in the context of controlling cell proliferation, give rise to an intricate molecular network, the understanding of which, in the future, will certainly be of help for the treatment of molecular diseases such as cancer.
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Affiliation(s)
- Marco De Martino
- Institute of Experimental Endocrinology and Oncology (IEOS) "G. Salvatore", National Research Council (CNR), Naples, Italy
| | - Francesco Esposito
- Institute of Experimental Endocrinology and Oncology (IEOS) "G. Salvatore", National Research Council (CNR), Naples, Italy
| | - Pierlorenzo Pallante
- Institute of Experimental Endocrinology and Oncology (IEOS) "G. Salvatore", National Research Council (CNR), Naples, Italy
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29
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Syllaios A, Moris D, Karachaliou GS, Sakellariou S, Karavokyros I, Gazouli M, Schizas D. Pathways and role of MALAT1 in esophageal and gastric cancer. Oncol Lett 2021; 21:343. [PMID: 33747200 PMCID: PMC7967938 DOI: 10.3892/ol.2021.12604] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 01/05/2021] [Indexed: 12/12/2022] Open
Abstract
Esophageal cancer (EC) and gastric cancer (GC) often have an unfavorable prognosis. Therefore, research is being conducted to identify the molecular mechanisms underlying the tumorigenesis and progression of GC and EC, and to indicate novel therapeutic targets and clinically applicable biomarkers. The dysregulations and roles of long non-coding RNAs (lncRNAs) have been widely reported, and current published literature has shown that lncRNAs play important regulatory roles in the carcinogenesis and progression of EC and GC. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been investigated in a number of studies with regard to its pathogenic pathways and association with the prognosis of gastric and esophageal malignancies. As literature on the topic of MALAT1 in EC and GC continues to emerge, the present review aims to summarize all current knowledge on the association between MALAT1 expression and esophagogastric malignancies and to describe the pathogenic pathways and possible prognostic role of MALAT1 in esophagogastric cancer. As research studies on MALAT1 pathways in esophagogastric malignancies are ongoing, new possibilities for the diagnosis, prognosis and therapy of GC and EC are likely to be identified.
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Affiliation(s)
- Athanasios Syllaios
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC 27707, USA
| | - Georgia Sofia Karachaliou
- Department of Medicine, Division of Hematology/Oncology, Duke University Medical Center, Durham, NC 27707, USA
| | - Stratigoula Sakellariou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Ioannis Karavokyros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
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30
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LncRNA MALAT1 promotes gastric cancer progression via inhibiting autophagic flux and inducing fibroblast activation. Cell Death Dis 2021; 12:368. [PMID: 33824303 PMCID: PMC8024309 DOI: 10.1038/s41419-021-03645-4] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/16/2021] [Accepted: 03/17/2021] [Indexed: 12/11/2022]
Abstract
Autophagy defection contributes to inflammation dysregulation, which plays an important role in gastric cancer (GC) progression. Various studies have demonstrated that long noncoding RNA could function as novel regulators of autophagy. Previously, long noncoding RNA MALAT1 was reported upregulated in GC cells and could positively regulate autophagy in various cancers. Here, we for the first time found that MALAT1 could promote interleukin-6 (IL-6) secretion in GC cells by blocking autophagic flux. Moreover, IL-6 induced by MALAT1 could activate normal to cancer-associated fibroblast conversion. The interaction between GC cells and cancer-associated fibroblasts in the tumour microenvironment could facilitate cancer progression. Mechanistically, MALAT1 overexpression destabilized the PTEN mRNA in GC cells by competitively interacting with the RNA-binding protein ELAVL1 to activate the AKT/mTOR pathway for impairing autophagic flux. As a consequence of autophagy inhibition, SQSTM1 accumulation promotes NF-κB translocation to elevate IL-6 expression. Overall, these results demonstrated that intercellular interaction between GC cells and fibroblasts was mediated by autophagy inhibition caused by increased MALAT1 that promotes GC progression, providing novel prevention and therapeutic strategies for GC.
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31
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Giaimo BD, Robert-Finestra T, Oswald F, Gribnau J, Borggrefe T. Chromatin Regulator SPEN/SHARP in X Inactivation and Disease. Cancers (Basel) 2021; 13:cancers13071665. [PMID: 33916248 PMCID: PMC8036811 DOI: 10.3390/cancers13071665] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/26/2021] [Accepted: 03/26/2021] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Carcinogenesis is a multistep process involving not only the activation of oncogenes and disabling tumor suppressor genes, but also epigenetic modulation of gene expression. X chromosome inactivation (XCI) is a paradigm to study heterochromatin formation and maintenance. The double dosage of X chromosomal genes in female mammals is incompatible with early development. XCI is an excellent model system for understanding the establishment of facultative heterochromatin initiated by the expression of a 17,000 nt long non-coding RNA, known as Xinactivespecifictranscript (Xist), on the X chromosome. This review focuses on the molecular mechanisms of how epigenetic modulators act in a step-wise manner to establish facultative heterochromatin, and we put these in the context of cancer biology and disease. An in depth understanding of XCI will allow a better characterization of particular types of cancer and hopefully facilitate the development of novel epigenetic therapies. Abstract Enzymes, such as histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, and DNA methyltransferases are known as epigenetic modifiers that are often implicated in tumorigenesis and disease. One of the best-studied chromatin-based mechanism is X chromosome inactivation (XCI), a process that establishes facultative heterochromatin on only one X chromosome in females and establishes the right dosage of gene expression. The specificity factor for this process is the long non-coding RNA Xinactivespecifictranscript (Xist), which is upregulated from one X chromosome in female cells. Subsequently, Xist is bound by the corepressor SHARP/SPEN, recruiting and/or activating histone deacetylases (HDACs), leading to the loss of active chromatin marks such as H3K27ac. In addition, polycomb complexes PRC1 and PRC2 establish wide-spread accumulation of H3K27me3 and H2AK119ub1 chromatin marks. The lack of active marks and establishment of repressive marks set the stage for DNA methyltransferases (DNMTs) to stably silence the X chromosome. Here, we will review the recent advances in understanding the molecular mechanisms of how heterochromatin formation is established and put this into the context of carcinogenesis and disease.
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Affiliation(s)
- Benedetto Daniele Giaimo
- Institute of Biochemistry, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany
- Correspondence: (B.D.G.); (T.B.); Tel.: +49-641-9947-400 (T.B.)
| | - Teresa Robert-Finestra
- Department of Developmental Biology, Erasmus MC, Oncode Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; (T.R.-F.); (J.G.)
| | - Franz Oswald
- Center for Internal Medicine, Department of Internal Medicine I, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany;
| | - Joost Gribnau
- Department of Developmental Biology, Erasmus MC, Oncode Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands; (T.R.-F.); (J.G.)
| | - Tilman Borggrefe
- Institute of Biochemistry, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany
- Correspondence: (B.D.G.); (T.B.); Tel.: +49-641-9947-400 (T.B.)
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Mou L, Liao L, Zhang Y, Ming D, Jiang J. Ursolic acid ameliorates Nthy-ori 3-1 cells injury induced by IL-1β through limiting MALAT1/miR-206/PTGS1 ceRNA network and NF-κB signaling pathway. Psychopharmacology (Berl) 2021; 238:1141-1156. [PMID: 33452572 DOI: 10.1007/s00213-021-05761-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 01/06/2021] [Indexed: 12/17/2022]
Abstract
RATIONALE Ursolic acid (UA) has exhibited anti-inflammatory and anti-oxidative drug effects. OBJECTIVES In the research, we assessed the effects of UA on Nthy-ori 3-1 cells stimulated by IL-1β and attempted to elucidate the mechanisms underlying the effects. METHODS Autoimmune thyroiditis (AIT) was simulated using Nthy-ori 3-1 cells by IL-1β (10 μM) treatment. UA (20 μM) was applied to ameliorate the injury of Nthy-ori 3-1 cells. The target of UA was predicted by TCMSP, BATMAN, and GEO database. Targeted relationship between lncRNA MALAT1 and miR-206, as well as miR-206 and PTGS1, was predicted by bioinformatics software and identified by dual luciferase assays. Cytokines in the cell supernatant and the apoptosis of cells were detected by ELISAs and flow cytometry assays, respectively. Expression levels of NF-κB signaling pathway-related proteins were estimated by western blot. RESULTS By enquiring TCMSP, BATMAN, and GEO database, PTGS1 was identified as a target of UA. Afterward, a ceRNA network among MALAT1, miR-206, and PTGS1 was constructed. The expression levels of MALAT1 and PTGS1 in AIT tissues were obviously enhanced. Moreover, the ceRNA network formed by MALAT1/miR-206/PTGS1 contributed to the damage of Nthy-ori 3-1 cells induced by IL-1β. However, UA ameliorated the Nthy-ori 3-1 cells injury induced by IL-1β through mediating the MALAT1/miR-206/PTGS1 ceRNA network and NF-κB signaling pathway. CONCLUSIONS UA treatment significantly relieved the injury of Nthy-ori 3-1 cells via inhibiting the ceRNA mechanism of MALAT1/miR-206/PTGS1 and inflammatory pathways, insinuating that UA may be helpful for the treatment of AIT.
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Affiliation(s)
- Lunpan Mou
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, No.250, Dongjie, Quanzhou, 362000, Fujian, China
| | - Liyan Liao
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yaping Zhang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, No.250, Dongjie, Quanzhou, 362000, Fujian, China
| | - Desong Ming
- Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
| | - Jianjia Jiang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, No.250, Dongjie, Quanzhou, 362000, Fujian, China.
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Goyal B, Yadav SRM, Awasthee N, Gupta S, Kunnumakkara AB, Gupta SC. Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer. Biochim Biophys Acta Rev Cancer 2021; 1875:188502. [PMID: 33428963 DOI: 10.1016/j.bbcan.2021.188502] [Citation(s) in RCA: 202] [Impact Index Per Article: 50.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/30/2020] [Accepted: 01/02/2021] [Indexed: 12/20/2022]
Abstract
Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is a widely studied lncRNA in cancer. Although dispensable for normal physiology, MALAT1 is important for cancer-related pathways regulation. It is localized in the nuclear speckles periphery along with centrally located pre-RNA splicing factors. MALAT1 associated cancer signaling pathways include MAPK/ERK, PI3K/AKT, β-catenin/Wnt, Hippo, VEGF, YAP, etc. Molecular tools such as immunoprecipitation, RNA pull-down, reporter assay, Northern blotting, microarray, and q-RT-PCR has been used to elucidate MALAT1's function in cancer pathogenesis. MALAT1 can regulate multiple steps in the development of tumours. The diagnostic and prognostic significance of MALAT1 has been demonstrated in cancers of the breast, cervix, colorectum, gallbladder, lung, ovary, pancreas, prostate, glioma, hepatocellular carcinoma, and multiple myeloma. MALAT1 has also emerged as a novel therapeutic target for solid as well as hematological malignancies. In experimental models, siRNA and antisense oligonucleotide (ASO) based strategy has been used for targeting MALAT1. The lncRNA has also been targeted for the chemosensitization and radiosensitization of cancer cells. However, most studies have been performed in preclinical models. How the cross-talk of MALAT1 with other signaling pathways affect cancer pathogenesis is the focus of this article. The diagnostic, prognostic, and therapeutic significance of MALAT1 in multiple cancer types are discussed.
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Affiliation(s)
- Bela Goyal
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Shashi Ranjan Mani Yadav
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Nikee Awasthee
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
| | - Sweety Gupta
- Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Ajaikumar B Kunnumakkara
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, 781039, India
| | - Subash Chandra Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
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Liu W, Zhang Y, Luo B. Long Non-coding RNAs in Gammaherpesvirus Infections: Their Roles in Tumorigenic Mechanisms. Front Microbiol 2021; 11:604536. [PMID: 33519750 PMCID: PMC7843584 DOI: 10.3389/fmicb.2020.604536] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) regulate gene expression at the epigenetic, transcriptional, or posttranscriptional level by interacting with protein, DNA, and RNA. Emerging evidence suggests that various lncRNAs are abnormally expressed and play indispensable roles in virus-triggered cancers. Besides, a growing number of studies have shown that virus-encoded lncRNAs participate in tumorigenesis. However, the functions of most lncRNAs in tumors caused by oncogenic viruses and their underlying mechanisms remain largely unknown. In this review, we summarize current findings regarding lncRNAs involved in cancers caused by Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV). Additionally, we discuss the contribution of lncRNAs to tumor occurrence, development, invasion, and metastasis; the roles of lncRNAs in key signaling pathways and their potential as biomarkers and therapeutic targets for tumor diagnostics and treatment.
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Affiliation(s)
- Wen Liu
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Yan Zhang
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China.,Department of Clinical Laboratory, Zibo Central Hospital, Zibo, China
| | - Bing Luo
- Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, China
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Sun W, Jiang C, Ji Y, Xiao C, Song H. Long Noncoding RNAs: New Regulators of Resistance to Systemic Therapies for Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2021; 2021:8853269. [PMID: 33506041 PMCID: PMC7808844 DOI: 10.1155/2021/8853269] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 12/07/2020] [Accepted: 12/19/2020] [Indexed: 02/07/2023]
Abstract
Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant disease, with approximately 951,000 new cases diagnosed and approximately 723,000 cases of mortality each year. The highest mortality rate of GC is in East Asia, and the lowest is in North America. A large number of studies have demonstrated that GC patients are characterized by higher morbidity, metastasis rates, and mortality and lower early diagnosis rates, radical resection rates, and 5-year survival rates. All cases of GC can be divided into two important stages, namely, early- and advanced-stage GC, and the stage mainly determines the treatment strategy for and the therapeutic effect in GC patients. Patients with early-stage GC undergo radical surgery followed by chemotherapy, and the 5-year survival rate can be as high as 90%. However, patients with advanced-stage GC cannot undergo radical surgery because they are at risk for metastasis; therefore, they can choose only radiotherapy or chemotherapy and have a poor prognosis. Based on the lack of specific clinical manifestations and detection methods, most GC patients (>70%) are diagnosed in the advanced stage; therefore, continued efforts toward developing treatments have been focused on advanced-stage GC patients and include molecular targeted therapy, immunotherapy, and small molecular therapy. Nevertheless, in recent years, accumulating evidence has indicated that small molecules, especially long noncoding RNAs (lncRNAs), are involved in the occurrence, development, and progression of GC, and their abundantly dysregulated expression has been identified in GC tissues and cell lines. Therefore, lncRNAs are considered easily detectable molecules and ideal biomarkers or target-specific agents for the future diagnosis or treatment of GC. In this review, we primarily discuss the status of GC, the role of lncRNAs in GC, and the emerging systemic treatments for GC.
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Affiliation(s)
- Weihong Sun
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
| | - Changqing Jiang
- Department of Pathology Qingdao Municipal Hospital, Donghai Middle Road, Qingdao 266071, China
| | - Ying Ji
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
| | - Chao Xiao
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
| | - Haiping Song
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
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Petkevicius V, Streleckiene G, Balciute K, Link A, Leja M, Malfertheiner P, Skieceviciene J, Kupcinskas J. Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis. Genes (Basel) 2020; 11:1505. [PMID: 33333725 PMCID: PMC7765138 DOI: 10.3390/genes11121505] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/09/2020] [Accepted: 12/10/2020] [Indexed: 02/07/2023] Open
Abstract
Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of MALAT1 rs3200401 CT genotype had the significantly higher odds of atrophic gastritis than those with CC genotype (OR-1.81; 95% CI 1.17-2.80, p = 0.0066). Higher odds of AG were found in a recessive model (CC vs. TT + CT) for ANRIL rs1333045 (OR-1.88; 95% CI 1.19-2.95, p = 0.0066). Carriers of ANRIL (rs17694493) GG genotype had higher odds of gastric cancer (OR-4.93; 95% CI 1.28-19.00) and atrophic gastritis (OR-5.11; 95% CI 1.10-23.80) compared with the CC genotype, and carriers of HOTAIR rs17840857 TG genotype had higher odds of atrophic gastritis (OR-1.61 95% CI 1.04-2.50) compared with the TT genotype; however, the ORs did not reach the adjusted significance threshold (p < 0.007). In summary, our data provide novel evidence for a possible link between lncRNA SNPs and premalignant condition of gastric cancer, suggesting the involvement of lncRNAs in gastric cancer development.
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Affiliation(s)
- Vytenis Petkevicius
- Department of Gastroenterology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania;
- Institute for Digestive Research, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (G.S.); (K.B.); (J.S.)
| | - Greta Streleckiene
- Institute for Digestive Research, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (G.S.); (K.B.); (J.S.)
| | - Kotryna Balciute
- Institute for Digestive Research, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (G.S.); (K.B.); (J.S.)
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; (A.L.); (P.M.)
| | - Marcis Leja
- Institute for Clinical and Preventive Medicine, Faculty of Medicine, University of Latvia,1586 Riga, Latvia;
- Faculty of Medicine, University of Latvia, 1586 Riga, Latvia
- Department of Research, Riga East University Hospital, 1079 Riga, Latvia
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; (A.L.); (P.M.)
| | - Jurgita Skieceviciene
- Institute for Digestive Research, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (G.S.); (K.B.); (J.S.)
| | - Juozas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania;
- Institute for Digestive Research, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (G.S.); (K.B.); (J.S.)
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Non-coding RNAs underlying chemoresistance in gastric cancer. Cell Oncol (Dordr) 2020; 43:961-988. [PMID: 32495294 DOI: 10.1007/s13402-020-00528-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 04/17/2020] [Accepted: 04/24/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is a major health issue in the Western world. Current clinical imperatives for this disease include the identification of more effective biomarkers to detect GC at early stages and enhance the prevention and treatment of metastatic and chemoresistant GC. The advent of non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long-non coding RNAs (lncRNAs), has led to a better understanding of the mechanisms by which GC cells acquire features of therapy resistance. ncRNAs play critical roles in normal physiology, but their dysregulation has been detected in a variety of cancers, including GC. A subset of ncRNAs is GC-specific, implying their potential application as biomarkers and/or therapeutic targets. Hence, evaluating the specific functions of ncRNAs will help to expand novel treatment options for GC. CONCLUSIONS In this review, we summarize some of the well-known ncRNAs that play a role in the development and progression of GC. We also review the application of such ncRNAs in clinical diagnostics and trials as potential biomarkers. Obviously, a deeper understanding of the biology and function of ncRNAs underlying chemoresistance can broaden horizons toward the development of personalized therapy against GC.
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Farooqi AA, Legaki E, Gazouli M, Rinaldi S, Berardi R. MALAT1 as a Versatile Regulator of Cancer: Overview of the updates from Predatory role as Competitive Endogenous RNA to Mechanistic Insights. Curr Cancer Drug Targets 2020; 21:CCDT-EPUB-108738. [PMID: 32748748 DOI: 10.2174/1568009620999200730183110] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 06/22/2020] [Accepted: 06/25/2020] [Indexed: 12/15/2022]
Abstract
The central dogma of molecular biology, has remained a cornerstone of classical molecular biology. However, serendipitously discovered microRNAs (miRNAs) in nematodes paradigmatically shifted our current knowledge of the intricate mechanisms during transitions from transcription to translation. The discovery of miRNA captured considerable attention and appreciation, and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets that are regulated by MALAT1 to stimulate or repress the expression of target genes. However, in this review, our main focus is to summarize mechanistic insights on MALAT1-mediated regulation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening. However, there is still a need to identify additional mechanisms. MALAT1 is involved in the multi-layered regulation of multiple transduction cascades, and detailed analysis of different pathways will be advantageous in getting a step closer to individualized medicine.
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Affiliation(s)
- Ammad Ahmad Farooqi
- Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 54000. Pakistan
| | - Evangelia Legaki
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens,. Greece
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens,. Greece
| | - Silvia Rinaldi
- Clinica Oncologica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I -GM Lancisi -G Salesi di Ancona, Via Conca 71, 60126 Ancona. Italy
| | - Rossana Berardi
- Clinica Oncologica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I -GM Lancisi -G Salesi di Ancona, Via Conca 71, 60126 Ancona. Italy
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Wang J, Wang X, Bhat A, Chen Y, Xu K, Mo YY, Yi SS, Zhou Y. Comprehensive Network Analysis Reveals Alternative Splicing-Related lncRNAs in Hepatocellular Carcinoma. Front Genet 2020; 11:659. [PMID: 32760422 PMCID: PMC7373802 DOI: 10.3389/fgene.2020.00659] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 05/29/2020] [Indexed: 01/18/2023] Open
Abstract
It is increasingly appreciated that long non-coding RNAs (lncRNAs) associated with alternative splicing (AS) could be involved in aggressive hepatocellular carcinoma. Although many recent studies show the alteration of RNA alternative splicing by deregulated lncRNAs in cancer, the extent to which and how lncRNAs impact alternative splicing at the genome scale remains largely elusive. We analyzed RNA-seq data obtained from 369 hepatocellular carcinomas (HCCs) and 160 normal liver tissues, quantified 198,619 isoform transcripts, and identified a total of 1,375 significant AS events in liver cancer. In order to predict novel AS-associated lncRNAs, we performed an integration of co-expression, protein-protein interaction (PPI) and epigenetic interaction networks that links lncRNA modulators (such as splicing factors, transcript factors, and miRNAs) along with their targeted AS genes in HCC. We developed a random walk-based multi-graphic (RWMG) model algorithm that prioritizes functional lncRNAs with their associated AS targets to computationally model the heterogeneous networks in HCC. RWMG shows a good performance evaluated by the ROC curve based on cross-validation and bootstrapping strategies. As a conclusion, our robust network-based framework has derived 31 AS-related lncRNAs that not only validates known cancer-associated cases MALAT1 and HOXA11-AS, but also reveals new players such as DNM1P35 and DLX6-AS1with potential functional implications. Survival analysis further provides insights into the clinical significance of identified lncRNAs.
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Affiliation(s)
- Junqing Wang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiuquan Wang
- Department of Mathematics and Computer Science, Tougaloo College, Jackson, MS, United States
| | - Akshay Bhat
- Department of Oncology and Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States
| | - Yixin Chen
- Department of Computer and Information Science, University of Mississippi, Oxford, MS, United States
| | - Keli Xu
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, United States
| | - Yin-yuan Mo
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, United States
| | - Song Stephen Yi
- Department of Oncology and Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States
| | - Yunyun Zhou
- Department of Data Science, University of Mississippi Medical Center, Jackson, MS, United States
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Down-regulation of lncRNA MALAT1 alleviates vascular lesion and vascular remodeling of rats with hypertension. Aging (Albany NY) 2020; 11:5192-5205. [PMID: 31343412 PMCID: PMC6682528 DOI: 10.18632/aging.102113] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 07/16/2019] [Indexed: 12/28/2022]
Abstract
Objective: Recently, the effect of long non-coding RNAs (lncRNAs) in hypertension (HTN) has been identified. This study aims to explore the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HTN and its role in vascular lesion and remodeling of HTN rats. Results: LncRNA MALAT1 expression was up-regulated in HTN patients, and lncRNA MALAT1 could be an effective index of HTN diagnosis. Down-regulated MALAT1 and inhibited Notch-1 could reduce relative factor expression, including inflammation-related factors, endothelial function-related factors and oxidative stress-related factors, and inhibit apoptosis of aortic endothelial cells of HTN rats. Methods: LncRNA MALAT1 expression in HTN patients and healthy controls was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Angiotensin II (Ang II)-induced HTN rat models were injected with MALAT1-siRNA, empty lentivirus vector, Notch pathway inhibitor (DAPT) and dimethyl sulphoxide (DMSO) via caudal vein. After three-week treatment, changes of blood pressure, inflammatory factor levels, endothelial function-related factors, oxidative stress indices and apoptosis of vascular endothelial cells were determined by a series of assays. Conclusion: This study revealed that down-regulated lncRNA MALAT1 could alleviate the vascular lesion and remodeling of HTN rats, the mechanism may be related to the inhibited activation of Notch signaling pathway.
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Sun YY, Zhang H, Ma RR, Zhang GH, Tian YR, Liu L, Liu L, Gao P. Long Non-coding RNA AK025387 Promotes Cell Migration and Invasion of Gastric Cancer. Front Oncol 2020; 10:633. [PMID: 32509569 PMCID: PMC7251172 DOI: 10.3389/fonc.2020.00633] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 04/06/2020] [Indexed: 12/19/2022] Open
Abstract
Gastric cancer is one of the most common cancers in the world, and long non-coding RNAs (lncRNAs) play a crucial role in proliferation, metastasis, and invasion of gastric cancer. However, there are very few researches focusing on the effects of lncRNAs on metastatic gastric cancer. In this research, we identify one kind of lncRNA, called AK025387, which is highly expressed in metastatic gastric cancer samples compared with non-metastatic gastric cancer samples. The expression of AK025387 is significantly positively correlated with lymph node metastasis. The in situ hybridization demonstrates that AK025387 is located in both nucleus and cytoplasm, but mostly in cytoplasm. AK025387 promotes gastric cancer cells migratory and invasive ability, but it inhibits apoptosis in vitro. Furthermore, AK025387 regulates Raf-1, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated kinase (ERK) and is involved in mitogen-activated protein kinase (MAPK) signaling pathway to perform its biological functions. We conclude that AK025387 is highly expressed in metastatic gastric cancer, and its biological functions suggest the potential of AK025387 to be a biomarker of metastatic gastric cancer.
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Affiliation(s)
- Yi-Yuan Sun
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Hui Zhang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Ran-Ran Ma
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Guo-Hao Zhang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Ya-Ru Tian
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lei Liu
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lin Liu
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Peng Gao
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, China.,Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
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Wang Y, Sun B, Wen X, Hao D, Du D, He G, Jiang X. The Roles of lncRNA in Cutaneous Squamous Cell Carcinoma. Front Oncol 2020; 10:158. [PMID: 32185124 PMCID: PMC7059100 DOI: 10.3389/fonc.2020.00158] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 01/29/2020] [Indexed: 02/05/2023] Open
Abstract
Cutaneous squamous cell carcinoma derives from keratinocytes and is the second most common cause of non-melanoma skin cancer. Cutaneous squamous cell carcinoma (cSCC) develops rapidly and is also the leading cause of death in non-melanoma cancers. Lymph node metastasis occurs in 5% of cSCC patients, and some patients may even metastasize to the viscera. Patients with regional lymphatic metastasis or distant metastases have a <20% 10-year survival rate, indicating the substantial challenge in treating advanced and metastatic cSCC. Some lncRNAs have been found to be abnormally overexpressed in many tumor tissues, so that they can be considered as potential new biomarkers or targets that can be used in the diagnosis and treatment of cSCC in the future. In this review, we summarize the role of lncRNA in cutaneous squamous cell carcinoma to make a better understanding of mutations in cSCC and lay the foundation for effective target therapy of cSCC.
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Affiliation(s)
- Yujia Wang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
| | - Bensen Sun
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiang Wen
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Hao
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Du
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
| | - Gu He
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xian Jiang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
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Esfandi F, Salehnezhad T, Taheri M, Afsharpad M, Hafez AA, Oskooei VK, Ghafouri-Fard S. Expression assessment of a panel of long non-coding RNAs in gastric malignancy. Exp Mol Pathol 2020; 113:104383. [PMID: 31982396 DOI: 10.1016/j.yexmp.2020.104383] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 12/24/2019] [Accepted: 01/23/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) have several important functions in the regulation of cell homeostasis and cell fate. Consequently, abnormal transcription of lncRNAs has been correlated with malignant transformation of cells. These human transcripts have been shown to participate in the progression of gastric cancer. METHODS In the current project, we evaluated expression of a panel of lncRNAs including HULC, MALAT1, FAS-AS1, GAS5, PVT1, OIP5-AS1 and THRIL in 30 gastric cancer tissues and paired adjacent non-cancerous tissues (ANCTs) using quantitative real-time PCR. RESULTS HULC, OIP5-AS1 and THRIL transcription quantities were significantly lower in gastric tumors compared to ANCTs (P values = .02, 0.02 and 0.007, respectively). Relative transcription quantities of HULC, MALAT1, OIP5-AS1, PVT1, FAS-AS1 and THRIL were associated with the site of the primary tumor (P values = .002, 0.003, 0.002, 0.002, 0.002, and 0.001, respectively). Moreover, relative expression levels of PVT1 were associated with history of smoking (P value = .04). Correlations were identified between transcript quantities of these lncRNAs in both tumor samples and ANCTs. Receiver operating characteristic curve assessment demonstrated that THRIL had the highest diagnostic power among the mentioned lncRNAs (area under curve (AUC) = 0.72, P value = .001). HULC and OIP5-AS1 ranked afterwards (AUC values of 0.69 and 0.68; P values = .005 and 0.007, respectively). CONCLUSION The current investigation underscores the dysregulation of these transcripts in gastric cancer specimens and suggests a number of these transcripts for further assessments of their suitability as cancer biomarkers.
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Affiliation(s)
- Farbod Esfandi
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tayebeh Salehnezhad
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mandana Afsharpad
- Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran
| | - Asghar Ashrafi Hafez
- Cancer Research Center, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Vahid Kholghi Oskooei
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Li X, Zhao J, Zhang H, Cai J. Silencing of LncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Inhibits the Proliferation and Promotes the Apoptosis of Gastric Cancer Cells Through Regulating microRNA-22-3p-Mediated ErbB3. Onco Targets Ther 2020; 13:559-571. [PMID: 32021298 PMCID: PMC6980870 DOI: 10.2147/ott.s222375] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 12/24/2019] [Indexed: 12/25/2022] Open
Abstract
PURPOSE This study aimed to investigate the regulatory effects and mechanisms of long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on gastric cancer (GC) cells. METHODS The expression of MALAT1 was detected in GC tissues and two GC cell lines (SGC-7901 and BGC-823). MALAT1 was overexpressed and silenced in GC cells by the transfection of pcDNA-MALAT1 and siRNA-MALAT1, respectively. The proliferation and apoptosis of transfected cells, as well as the tumor volume and weight in mice injected with transfected cells were determined. After identifying the interaction between microRNA-22-3p (miR-22-3p) and MALAT1/epidermal growth factor receptor 3 (ErbB3), the effects of miR-22-3p/ErbB3 silencing on the proliferation and apoptosis of GC cells were evaluated. RESULTS MALAT1 was significantly upregulated in GC tissues and cells and negatively associated with the survival of GC patients. Overexpression of MALAT1 significantly promoted the proliferation and inhibited the apoptosis of SGC-7901 cells, while silencing of MALAT1 exerts contrary effects on BGC-823 cells. Silencing of MALAT1 also significantly inhibited the tumor growth in mice. In addition, MALAT1 negatively regulated its target miR-22-3p. Silencing of miR-22-3p reversed the anti-tumor effects of MALAT1 silencing on GC cells. MiR-22-3p negatively regulated its target ErbB3. Silencing of ErbB3 reversed the tumor-promoting effects of miR-22-3p silencing on GC cells. CONCLUSION Silencing of MALAT1 inhibited the proliferation and promoted the apoptosis of GC cells through upregulating miR-22-3p and downregulating ErbB3.
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Affiliation(s)
- Xiaoning Li
- Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei050017, People’s Republic of China
- Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei050051, People’s Republic of China
- Department of General SurgeryⅡ, Baoding First Central Hospital, Baoding, Hebei071000, People’s Republic of China
| | - Jiangqiao Zhao
- Department of General Surgery, Cangzhou People’s Hospital, Cangzhou, Hebei061000, People’s Republic of China
| | - Huiqing Zhang
- Department of Medical, Baoding First Central Hospital, Baoding, Hebei, People’s Republic of China
| | - Jianhui Cai
- Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei050017, People’s Republic of China
- Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei050051, People’s Republic of China
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Shao G, Zhao Z, Zhao W, Hu G, Zhang L, Li W, Xing C, Zhang X. Long non-coding RNA MALAT1 activates autophagy and promotes cell proliferation by downregulating microRNA-204 expression in gastric cancer. Oncol Lett 2020; 19:805-812. [PMID: 31897197 PMCID: PMC6924198 DOI: 10.3892/ol.2019.11184] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Accepted: 11/01/2019] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is one of the major diseases that threaten human health. Although the development of novel drugs has significantly improved the efficacy of GC chemotherapy, the 5-year survival rate of patients with GC remains unsatisfactory. In the present study, the role and mechanism of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in GC proliferation was investigated. Clinical specimens and cancer cells were analyzed by western blotting or immunofluorescence. Reverse transcription-quantitative polymerase chain reaction analysis of 57 paired GC and non-tumorous tissues revealed elevated expression of MALAT1 in GC tissues compared with controls. In addition, increased MALAT1 was associated with elevated levels of microtubule-associated protein 1 light chain 3β (LC3B) and antigen Ki67, which are autophagy and proliferation markers, respectively. MTT and colony formation assay results demonstrated that MALAT1 promoted GC cell proliferation. To the best of our knowledge, the present study was the first to demonstrate that upregulated MALAT1 was associated with increased autophagy activation in GC tissues. Furthermore, this study reported that MALAT1 increased cell proliferation and enhanced autophagy activation in GC cells. In addition, the results revealed that MALAT1 inhibited microRNA (miR)-204 expression in GC cells. The present study also demonstrated that miR-204 repressed autophagy through the downregulation of LC3B and transient receptor potential melastatin 3 expression in GC cells. These results indicated that MALAT1 activated autophagy and promoted cell proliferation by downregulating miR-204 expression in GC.
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Affiliation(s)
- Guoyi Shao
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
- Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, Jiangsu 214400, P.R. China
| | - Zhenguo Zhao
- Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, Jiangsu 214400, P.R. China
| | - Wei Zhao
- Department of Clinical Biochemistry, School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan 610000, P.R. China
| | - Gen Hu
- Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, Jiangsu 214400, P.R. China
| | - Liying Zhang
- Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, Jiangsu 214400, P.R. China
| | - Wei Li
- Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, Jiangsu 214400, P.R. China
| | - Chungen Xing
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
| | - Xian Zhang
- Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, Jiangsu 214400, P.R. China
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Ghafouri-Fard S, Taheri M. Long non-coding RNA signature in gastric cancer. Exp Mol Pathol 2019; 113:104365. [PMID: 31899194 DOI: 10.1016/j.yexmp.2019.104365] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 12/18/2019] [Accepted: 12/28/2019] [Indexed: 02/07/2023]
Abstract
Gastric cancer as a common human malignancy has been associated with aberrant expressions of several coding and non-coding genes. Long non-coding RNAs (lncRNAs) as regulators of gene expressions at different genomic, transcriptomic and post-transcriptomic levels are among putative biomarkers and therapeutic targets in gastric cancer. In the present study, we have searched available literature and listed lncRNAs that are involved in the pathogenesis of gastric cancer. In addition, we discuss associations between expressions of these lncRNAs and tumoral features or risk factors for gastric cancer. Based on the established role of lncRNAs in regulation of genomic stability, cell cycle, apoptosis, angiogenesis and other aspects of cell physiology, the potential of these transcripts as therapeutic targets in gastric cancer should be evaluated in future studies.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Tiansheng G, Junming H, Xiaoyun W, Peixi C, Shaoshan D, Qianping C. lncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes Proliferation and Invasion of Non-Small Cell Lung Cancer Cells via Down-Regulating miR-202 Expression. CELL JOURNAL 2019; 22:375-385. [PMID: 31863664 PMCID: PMC6947012 DOI: 10.22074/cellj.2020.6837] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 02/06/2019] [Indexed: 12/27/2022]
Abstract
Objective Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play key roles in cancer. This study
aims to clarify role of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in non-small cell lung
cancer (NSCLC) and uncover the underlying mechanisms.
Materials and Methods In this experimental study, MALAT1 and miR-202 expression in tissues and cell lines were
detected using quantitative real time polymerase chain reaction (qRT-PCR) assay. Cell transfection was conducted
using Lipofectamine 3000. Cell proliferation was determined with CCK-8 assay. MMP2 and MMP9 expressions were
measured with Western blot. Cell invasive ability was evaluated by Transwell assay. Starbase 2.0 tool was used to
predict targets of MALAT1. Dual luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA
pull-down assay were conducted to confirm the potential direct interaction between MALAT1 and miR-202.
Results MALAT1 was overexpressed in NSCLC samples and cell lines. High expression of MALAT1 was related
to large tumor size (>3 cm), poor histological grade, advanced cancer and tumor metastasis in NSCLC. In vitro
assays exhibited that knockdown of MALAT1 remarkably decreased A549 cell growth and invasion capacity, while
overexpression of MALAT1 significantly enhanced NCI-H292 cell proliferation and invasion ability. Next, we verified that
MALAT1 could act as a competing endogenous RNA (ceRNA) by sponging miR-202 in NSCLC and there is a negative
correlation between MALAT1 and miR-202. Besides, overexpression of miR-202 inhibited cell proliferation and invasive
ability in MALAT1-overexpressed cells.
Conclusion This study demonstrated that lncRNA-MALAT1 gets involved in NSCLC progression by targeting miR-
202, indicating that MALAT1 may serve as a novel therapeutic target for NSCLC treatment.
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Affiliation(s)
- Guo Tiansheng
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China. Electronic Address:
| | - Huang Junming
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China. Electronic Address:
| | - Wan Xiaoyun
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China. Electronic Address:
| | - Chen Peixi
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China
| | - Du Shaoshan
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China
| | - Chen Qianping
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China
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Wang Y, Yang F, Yang Q. The regulatory roles and potential prognosis implications of long non-coding RNAs in gastric cancer. Histol Histopathol 2019; 35:433-442. [PMID: 31793657 DOI: 10.14670/hh-18-188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Accumulating dysregulated lncRNAs have been demonstrated to execute vital functions in the pathogenesis and progress of gastric cancer (GC) through versatile molecular mechanisms. In this review, we classify the mechanisms of dysregulated lncRNAs in GC into several governing types according to their roles at molecular level. For each regulatory role, we illustrate several instructive examples and introduce significant effects of lncRNAs on cellular biological properties of GC. Besides, we summarize a group of lncRNA-signatures that are potential biomarkers in the prediction of prognosis for GC patients.
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Affiliation(s)
- Yue Wang
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun City, Jilin Province, China
| | - Fan Yang
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun City, Jilin Province, China
| | - Qing Yang
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun City, Jilin Province, China.
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Li X, Na H, Xu L, Zhang X, Feng Z, Zhou X, Cui J, Zhang J, Lin F, Yang S, Yue F, Mousa H, Zuo Y. DC-SIGN mediates gastric cancer progression by regulating the JAK2/STAT3 signaling pathway and affecting LncRNA RP11-181G12.2 expression. Biomed Pharmacother 2019; 121:109644. [PMID: 31766099 DOI: 10.1016/j.biopha.2019.109644] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 11/01/2019] [Accepted: 11/01/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The molecular mechanisms of gastric cancer (GC) development are very complicated. Recent studies revealed that DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein (DC-SIGNR) is involved in colon cancer and GC biological processes. However, the exact roles of DC-SIGN in GC remain unrevealed. METHODS DC-SIGN overexpression and knockdown experiments were performed by using DC-SIGN shRNA or DC-SIGN plasmid to investigate the biological roles of DC-SIGN in proliferation, cell cycle progression, migration and invasion of GC cells in vitro. Furthermore, the lncRNA profiles of SGC-7901 cells with control shRNA and DC-SIGN shRNA were generated by using microarray analysis. Mechanistically, the relationship between DC-SIGN, RP11-181G12.2 and the JAK2/STAT3 signaling pathway was then investigated using qRT-PCR and western blot assays. Additionally, we analyzed DC-SIGN and RP11-181G12.2 expression levels in GC specimens based on the Cancer Genome Atlas database. RESULTS In this study, the results showed that DC-SIGN was highly expressed in GC cells and significantly correlated with advanced clinical stage and lymphatic metastasis. Downregulation of DC-SIGN significantly inhibited the proliferation, cell cycle progression, migration and invasion of GC cells in vitro. The reverse results could partly be seen with the upregulation of DC-SIGN. Mechanistically, knockdown of DC-SIGN inactivated the JAK2/STAT3 signaling pathway, and overexpression of DC-SIGN activated the JAK2/STAT3 signaling pathway. In addition, through LncPath microarray analysis, we identified a lncRNA, RP11-181G12.2, that was significantly upregulated after knockdown of DC-SIGN; this was also confirmed by qRT-PCR. Furthermore, RP11-181G12.2 knockdown enhanced DC-SIGN expression in GC cells, further activating the JAK2/STAT3 signaling pathway. In contrast, DC-SIGN overexpression suppressed RP11-181G12.2 expression. CONCLUSIONS Our study suggests that DC-SIGN might be involved in the progression of GC by regulating the JAK2/STAT3 signaling pathway and affecting lncRNA RP11-181G12.2 expression.
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Affiliation(s)
- Xiaomeng Li
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Heya Na
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China; Department of Laboratory Medicine, The People's Hospital of Liaoning Province, Shenyang, 110016, China.
| | - Lijie Xu
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Xinsheng Zhang
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116044, China.
| | - Zhen Feng
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116044, China.
| | - Xu Zhou
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Jingyi Cui
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Jingbo Zhang
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Fang Lin
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Shiqing Yang
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Fangxia Yue
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Haithm Mousa
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
| | - Yunfei Zuo
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
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Metastasis Associated Lung Adenocarcinoma Transcript 1: An update on expression pattern and functions in carcinogenesis. Exp Mol Pathol 2019; 112:104330. [PMID: 31712117 DOI: 10.1016/j.yexmp.2019.104330] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 11/03/2019] [Indexed: 12/28/2022]
Abstract
The Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is among long non-coding RNAs (lncRNAs) which has disapproved the old term of "junk DNA" which was used for majority of human genome which are not transcribed to proteins. An extensive portion of literature points to the fundamental role of this lncRNA in tumorigenesis process of diverse cancers ranging from solid tumors to leukemia. Being firstly identified in lung cancer, it has prognostic and diagnostic values in several cancer types. Consistent with the proposed oncogenic roles for this lncRNA, most of studies have shown up-regulation of MALAT1 in malignant tissues compared with non-malignant/normal tissues of the same source. However, few studies have shown down-regulation of MALAT1 in breast cancer, endometrial cancer, colorectal cancer and glioma. In the current study, we have conducted a comprehensive literature search and provided an up-date on the role of MALAT1 in cancer biology. Our investigation underscores a potential role as a diagnostic/prognostic marker and a putative therapeutic target for MALAT1.
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