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Kwas K, Szubert M, Wilczyński JR. Latest Update on lncRNA in Epithelial Ovarian Cancer-A Scoping Review. Cells 2025; 14:555. [PMID: 40214508 PMCID: PMC11988607 DOI: 10.3390/cells14070555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/22/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025] Open
Abstract
Long noncoding RNAs (lncRNAs) are RNA molecules exceeding 200 nucleotides that do not encode proteins yet play critical roles in regulating gene expression at multiple levels, such as chromatin modification and transcription. These molecules are significantly engaged in cancer progression, development, metastasis, and chemoresistance. However, the function of lncRNAs in epithelial ovarian cancer (EOC) has not yet been thoroughly studied. EOC remains challenging due to its complex molecular pathogenesis, characterized by genetic and epigenetic alterations. Emerging evidence suggests that lncRNAs, such as XIST, H19, NEAT1, and MALAT1, are involved in EOC by modulating gene expression and signaling pathways, influencing processes like cell proliferation, invasion, migration, and chemoresistance. Despite extensive research, the precise mechanism of acting of lncRNAs in EOC pathogenesis and treatment resistance still needs to be fully understood, highlighting the need for further studies. This review aims to provide an updated overview of the current understanding of lncRNAs in EOC, emphasizing their potential as biomarkers and therapeutic targets. We point out the gaps in the knowledge regarding lncRNAs' influence on epithelial ovarian cancer (EOC), deliberating on new possible research areas.
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Affiliation(s)
- Katarzyna Kwas
- Department of Surgical and Oncologic Gynaecology, 1st Department of Gynaecology and Obstetrics, Medical University of Lodz, 90-136 Łódź, Poland; (M.S.); (J.R.W.)
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Li K, Liu W, Zhao X, Lin W, Zhou W, Zhang Q. LncRNA SNHG3 discriminates rheumatoid arthritis from healthy individuals and regulates inflammatory response and oxidative stress via modulating miR-128-3p. Mod Rheumatol 2024; 34:1153-1161. [PMID: 38722030 DOI: 10.1093/mr/roae042] [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: 11/08/2023] [Accepted: 04/25/2024] [Indexed: 10/17/2024]
Abstract
OBJECTIVES This study evaluated the expression and significance of SNHG3 in rheumatoid arthritis (RA), aiming to explore a biomarker and regulator for RA. METHODS The expression of SNHG3 in serum and synovial tissue was compared between RA patients and healthy individuals using polymerase chain reaction (PCR). The RA animal models were induced by the Porcine Type II collagen in Wistar rats and validated by the foot volume and arthritis index score. The human fibroblast-like synoviocytes were treated with lipopolysaccharide (LPS) to mimic the injury during RA onset, and the cell growth was assessed by cell counting kit-8 (CCK8) assay. RESULTS SNHG3 was significantly downregulated in the serum and synovial tissue of RA patients compared with healthy individuals. Downregulated SNHG3 could discriminate RA patients from healthy individuals with high sensitivity (0.875) and specificity (0.844). Porcine Type II collagen induced increasing foot volume and arthritis index scores of rats, and SNHG3 was downregulated in RA rats. In LPS-induced human fibroblast-like synoviocytes, SNHG3 negatively regulated miR-128-3p, and the alleviated effect of SNHG3 overexpression on cellular inflammation and oxidative stress was reversed by miR-128-3p upregulation. CONCLUSIONS Serum SNHG3 was considered a potential diagnostic biomarker for RA from healthy individuals. SNHG3 regulated inflammatory response and oxidative stress by negatively modulating miR-128-3p.
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Affiliation(s)
- Kejun Li
- Department of Orthopaedics, Hangzhou 9th People's Hospital, Hangzhou, Zhejiang, China
| | - Wei Liu
- Comprehensive Orthopedics, Affiliated Hospital of Hebei University, Baoding, Hebei, China
| | - Xueru Zhao
- Department of Joint Surgery, Lishui People's Hospital, Lishui, Zhejiang, China
| | - Weiyi Lin
- Department of Emergency Medicine, Lishui Municipal Central Hospital, Lishui, Zhejiang, China
| | - Wenhui Zhou
- Department of Joint Surgery, Lishui People's Hospital, Lishui, Zhejiang, China
| | - Qi Zhang
- Department of Orthopaedics, Chongqing Public Health Medical Center, Chongqing, China
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Peng Y, Long XD. The role of the ceRNA network mediated by lncRNA SNHG3 in the progression of cancer. Discov Oncol 2024; 15:514. [PMID: 39349640 PMCID: PMC11442963 DOI: 10.1007/s12672-024-01184-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 07/22/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) are a distinct class of RNAs with longer than 200 base pairs that are not translated into proteins. Small Nucleolar RNA Host Gene 3 (SNHG3) is a lncRNA and frequently dysregulated in various human cancers. OBJECTIVE This review provides a comprehensive analysis of current research on lncRNA SNHG3, focusing on its role within the competitive endogenous RNA (ceRNA) network and its implications in cancer. METHODS A systematic literature review was conducted using PubMed up to October 2023. The search strategy included keywords such as "lncRNA SNHG3", "competitive endogenous RNA", "cancer", and related terms. Studies were selected based on relevance to SNHG3's involvement in cancer pathogenesis and progression. RESULTS Disruptions in the ceRNA network involving lncRNA SNHG3 can impair normal cell growth and differentiation, significantly contributing to disease pathogenesis, particularly cancer. This review highlights SNHG3's substantial impact on various cancer processes and its potential as a diagnostic and therapeutic tool for aggressive cancers. CONCLUSION The findings underscore SNHG3's pivotal role in cancer prevention, diagnosis, and treatment, laying a foundation for future research in cancer management. Insights from this review emphasize the necessity for further exploration and development of SNHG3-based diagnostic and therapeutic strategies.
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Affiliation(s)
- Ying Peng
- Department of Pathology, the First Affiliated Hospital, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
- Department of Pathology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518000, Guangdong, People's Republic of China
- Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise, 533000, People's Republic of China
| | - Xi-Dai Long
- Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise, 533000, People's Republic of China.
- Department of Tumor Pathology, Key Laboratory of Tumor Molecular Pathology of Guangxi Higher Education Institutes, Guangxi Zhuang Autonomous Region, Baise, 533000, China.
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Tan S, Chen X, Liu W. Tumor-suppressive role of miR-139-5p in angiogenesis and tumorigenesis of ovarian cancer: Based on GEO microarray analysis and experimental validation. Cell Signal 2023; 109:110730. [PMID: 37244634 DOI: 10.1016/j.cellsig.2023.110730] [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: 03/07/2023] [Revised: 05/03/2023] [Accepted: 05/21/2023] [Indexed: 05/29/2023]
Abstract
This study clarified the possible molecular mechanisms by which the miR-139-5p/SOX4/TMEM2 axis affected angiogenesis and tumorigenesis of ovarian cancer (OC) based on GEO microarray datasets and experimental support. The expression of miR-139-5p and SOX4 was examined in clinical OC samples. Human umbilical vein endothelial cells (HUVECs) and human OC cell lines were included in vitro experiments. Tube formation assay was conducted in HUVECs. The expression of SOX4, SOX4, and VEGF in OC cells was identified using Western blot and immunohistochemistry. Luciferase assays were conducted to validate the targeting relationship between miR-139-5p and SOX4 and between SOX4 and TMEM2. A RIP assay assessed the binding of SOX4 and miR-139-5p. The impact of miR-139-5p and SOX4 on OC tumorigenesis in vivo was evaluated in nude mice. SOX4 was up-regulated, while miR-139-5p was down-regulated in OC tissues and cells. Ectopic miR-139-5p expression or SOX4 knockdown inhibited angiogenesis and tumorigenicity of OC. By targeting SOX4 in OC, miR-139-5p lowered VEGF expression, angiogenesis, and TMEM2 expression. The miR-139-5p/SOX4/TMEM2 axis also reduced VEGF expression and angiogenesis, which might curtail OC growth in vivo. Collectively, miR-139-5p represses VEGF expression and angiogenesis by targeting the transcription factor SOX4 and down-regulating TMEM2 expression, thereby impeding OC tumorigenesis.
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Affiliation(s)
- Shu Tan
- Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China
| | - Xiuwei Chen
- Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China
| | - Wei Liu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
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Zhao M, Li N, Wan C, Zhang Q, Wang H, Jiang C. LncRNA CRNDE is involved in the pathogenesis of renal fibrosis by regulating renal epithelial cell mesenchymal-epithelial transition via targeting miR-29a-3p. Mutat Res 2023; 826:111817. [PMID: 37178498 DOI: 10.1016/j.mrfmmm.2023.111817] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/04/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023]
Abstract
Results of previous studies suggested that renal fibrosis and epithelial-mesenchymal transition (EMT) plays an important role in the process of renal fibrosis, but the underlying mechanism remains unclear. Long coding RNA (lncRNA) CRNDE has emerged as potent regulators of EMT programs, therefore, in present work, we examined the roles of LncRNA CRNDE/miR-29a-3p axis in renal fibrosis and the underlying mechanism. We found that in both renal fibrosis animal and cell models, lncRNA CRNDE was dynamically upregulated in animal models or cells by the treatment of TGF-β. Furthermore, knockdown of CRNDE to rat significantly inhibited EMT, prevented renal fibrosis. Finally, CRNDE regulates renal fibrosis through suppression of miR-29a-3p expression. Together, our results demonstrated that CRNDE acted as a regulator of renal fibrosis via targeting miR-29a-3p. Our findings may provide a potential therapeutic target for the treatment of renal fibrosis.
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Affiliation(s)
- Min Zhao
- Department of Nephrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No.321, Zhongshan Road, Nanjing 210008, Jiangsu, PR China
| | - Nan Li
- Department of Nephrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No.321, Zhongshan Road, Nanjing 210008, Jiangsu, PR China
| | - Cheng Wan
- Department of Nephrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No.321, Zhongshan Road, Nanjing 210008, Jiangsu, PR China
| | - Qingyan Zhang
- Department of Nephrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No.321, Zhongshan Road, Nanjing 210008, Jiangsu, PR China
| | - Hengjin Wang
- Department of Nephrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No.321, Zhongshan Road, Nanjing 210008, Jiangsu, PR China.
| | - Chunming Jiang
- Department of Nephrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No.321, Zhongshan Road, Nanjing 210008, Jiangsu, PR China.
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Wu Y, Li M, Bai J, Ma X. Silencing long non-coding RNA SNHG3 repairs the dysfunction of pulmonary microvascular endothelial barrier by regulating miR-186-5p/Wnt axis. Biochem Biophys Res Commun 2023; 639:36-45. [PMID: 36463759 DOI: 10.1016/j.bbrc.2022.11.067] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 11/22/2022] [Accepted: 11/23/2022] [Indexed: 11/25/2022]
Abstract
Barrier permeability changes of human pulmonary microvascular endothelial cells (HPMVECs) are important in sepsis-related acute lung injury (ALI) pathogenesis. Long non-coding small nucleolar RNA host gene 3 (SNHG3) mediates the cell-biological phenotype of lung cancer cells and affects the progression of lung cancer, but its role in regulating functions of lung non-malignant cells is still rarely reported. Therefore, we evaluated the regulatory effect of SNHG3 on the function of PMVECs in sepsis-related ALI. Small interference RNA (siRNA)-mediated deletion of SNHG3 promoted the proliferation of PMVECs, reduced apoptosis and barrier permeability, and increased the expression of tight junction proteins claudin-5 and ZO-1. Knockdown of SNHG3 increased the miR-186-5p expression, while overexpression of SNHG3 upregulated the level of wnt5a. Through a dual luciferase reporter assay, we confirmed the binding between SNHG3 and miR-186-5p, miR-186-5p and wnt5a. We further found that knockout of miR-186-5p could inhibit cell proliferation, increase apoptosis and barrier permeability, and down-regulate claudin-5 and ZO-1. Importantly, silencing miR-186-5p and activating Wnt signal pathway could eliminate the barrier repair effect caused by down-regulation of SNHG3. To sum up, our results suggested that knockdown of long non-coding RNA SNHG3 repaired the dysfunction of pulmonary microvascular endothelial barrier through the miR-186-5p/Wnt axis.
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Affiliation(s)
- Yanli Wu
- Department of Critical Care Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China; Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China
| | - Mei Li
- Department of Critical Care Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China
| | - Jijia Bai
- Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China
| | - Xigang Ma
- Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China.
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Hashemi M, Hasani S, Hajimazdarany S, Mirmazloomi SR, Makvandy S, Zabihi A, Goldoost Y, Gholinia N, Kakavand A, Tavakolpournegari A, Salimimoghadam S, Nabavi N, Zarrabi A, Taheriazam A, Entezari M, Hushmandi K. Non-coding RNAs targeting notch signaling pathway in cancer: From proliferation to cancer therapy resistance. Int J Biol Macromol 2022; 222:1151-1167. [DOI: 10.1016/j.ijbiomac.2022.09.203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 09/22/2022] [Indexed: 11/26/2022]
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Qiu H, Liu M, Shi X, Ma M, Zhang J, Liu H. LncRNA HOTAIR inhibits the progression of fibroblast-like synoviocytes by sponging miRNA-106b-5p in rheumatoid arthritis. Autoimmunity 2022; 55:567-576. [PMID: 36164683 DOI: 10.1080/08916934.2022.2126460] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease of unknown etiology. Human fibroblast-like synoviocytes (HFLSs) are the main effector cells for synovial hyperplasia and invasion in RA. Long non-coding RNAs (lncRNAs) play key roles in several autoimmune diseases, including RA. We investigated the effects of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) on the pathological behavior of HFLSs in RA. The microRNAs (miRNAs) with potential binding sites for lncRNA HOTAIR were predicted using Starbase v2.0. TargetScan (http://www.targetscan.org) was used to analyze the potential target genes of miR-106b-5p. The interactions were further verified using a dual-luciferase reporter assay. RNA and protein expression was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. The proliferation, cell invasion and migration, and cell apoptosis of HFLSs in RA was detected by the 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry (FCM). The dual luciferase reporter assay confirmed the interactions between lncRNA HOTAIR and miR-106b-5p and between miR-106b-5p and SMAD family member 7 (SMAD7). The qRT-PCR results indicated that the expression of lncRNA HOTAIR was markedly decreased and that of miR-106b-5p was markedly increased in HFLSs of RA. Cell proliferation, invasion, and migration of HFLSs were inhibited by lncRNA HOTAIR upregulation, and the expression of miR-106b-5p was negatively regulated by lncRNA HOTAIR in HFLSs. Apoptosis of HFLS cells was improved by the overexpression of lncRNA HOTAIR. All the effects of lncRNA HOTAIR upregulation on HFLSs were reversed after the overexpression of miR-106b-5p. Smad7 was identified as a target gene of miR-106b-5p, and the effects of downregulation of miR-106b-5p on HFLSs could be abolished by silencing Smad7. We found that lncRNA HOTAIR was significantly downregulated in the HFLSs of patients with RA. Moreover, lncRNA HOTAIR influenced cell growth, migration, invasion, and apoptosis in HFLSs through the miR-106b-5p/Smad7 axis.
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Affiliation(s)
- Hongxia Qiu
- Department of Rheumatology, Xi'an No.5 Hospital, Xi'an, China.,Medical Department, Hospital of Northwest Polytechnic University, Xi'an, China
| | - Meixia Liu
- Department of Rehabilitation and Physical Therapy, Zaozhuang Municipal Hospital, Zaozhuang, China
| | - Xuefei Shi
- Department of Rheumatology, Xi'an No.5 Hospital, Xi'an, China
| | - Miao Ma
- Department of Rheumatology, Xi'an No.5 Hospital, Xi'an, China
| | - Jing Zhang
- Department of Rheumatology, Xi'an No.5 Hospital, Xi'an, China
| | - Hua Liu
- Department of Rheumatology, Xi'an No.5 Hospital, Xi'an, China
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Chen L, Liu H, Sun C, Pei J, Li J, Li Y, Wei K, Wang X, Wang P, Li F, Gai S, Zhao Y, Zheng Z. A Novel LncRNA SNHG3 Promotes Osteoblast Differentiation Through BMP2 Upregulation in Aortic Valve Calcification. JACC Basic Transl Sci 2022; 7:899-914. [PMID: 36317131 PMCID: PMC9617132 DOI: 10.1016/j.jacbts.2022.06.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 06/15/2022] [Accepted: 06/15/2022] [Indexed: 11/30/2022]
Abstract
The long noncoding RNA SNHG3 was upregulated in the leaflets of both patients and mice with calcific aortic valve disease. SNHG3 can associate with EZH2 in the nucleus of hVICs to epigenetically upregulate BMP2, a key mediator of calcification. SNHG3 promoted osteoblast differentiation of hVICs via upregulation of the BMP2 pathway. SNHG3 silencing significantly ameliorated aortic valve calcification in experimental animals, providing a novel therapeutic target for CAVD. Based on high-throughput transcriptomic sequencing, SNHG3 was among the most highly expressed long noncoding RNAs in calcific aortic valve disease. SNHG3 upregulation was verified in human and mouse calcified aortic valves. Moreover, in vivo and in vitro studies showed SNHG3 silencing markedly ameliorated aortic valve calcification. In-depth functional assays showed SNHG3 physically interacted with polycomb repressive complex 2 to suppress the H3K27 trimethylation BMP2 locus, which in turn activated BMP2 expression and signaling pathways. Taken together, SNHG3 promoted aortic valve calcification by upregulating BMP2, which might be a novel therapeutic target in human calcific aortic valve disease.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Zhe Zheng
- Address for correspondence: Dr Zhe Zheng, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, PR China.
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Chen L, Wei K, Li J, Li Y, Cao H, Zheng Z. Integrated Analysis of LncRNA-Mediated ceRNA Network in Calcific Aortic Valve Disease. Cells 2022; 11:2204. [PMID: 35883646 PMCID: PMC9315639 DOI: 10.3390/cells11142204] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 06/24/2022] [Accepted: 06/27/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The high morbidity and mortality of calcific aortic valve disease (CAVD) represents an unmet clinical need to investigate the molecular mechanisms involved. Evidence suggests that long non-coding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) by binding to microRNAs and regulating target genes in cardiovascular diseases. Nevertheless, the role of lncRNAs related ceRNA regulation in CAVD remains unclear. METHODS RNAseq data of human diseased aortic valves were downloaded from GEO data sets (GSE153555, GSE199718), and differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs) between CAVD and non-calcific aortic valve tissues with limma R package. Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Set Enrichment analysis (GSEA) were performed with clusterProfiler and gesaplot2 R package. The pivotal microRNAs were predicted by three databases intersection including TargetScan, MiRwalk, miRDB according to the genes related to the crucial pathways. ENCORI was used to predict targeted lncRNAs of hub microRNAs. We constructed lncRNA-miRNA-mRNA ceRNA network with Cytoscape software. The lncRNAs in ceRNA network were verified by RT-qPCR in human 30 calcific and 20 noncalcified aortic valve tissues. RESULTS In total, 1739 DEmRNAs and 266 DElncRNAs were identified in CAVD. GO, KEGG pathway, GSEA annotations suggested that most of these genes are enriched in extracellular matrix (ECM)-reporter interaction pathways. The ceRNA networks associated with ECM-reporter interaction are constructed and related lncRNAs including H19, SNHG3 and ZNF436-AS1 were significant upregulated in human calcific aortic valve tissues, which might be potential therapeutic targets for CAVD. CONCLUSIONS In this study, we proposed a novel lncRNA-miRNA-mRNA ceRNA network related to ECM-reporter interaction pathways, which potentially regulates CAVD progression.
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Affiliation(s)
- Long Chen
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (L.C.); (K.W.); (J.L.); (Y.L.)
| | - Ke Wei
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (L.C.); (K.W.); (J.L.); (Y.L.)
| | - Jun Li
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (L.C.); (K.W.); (J.L.); (Y.L.)
| | - Yue Li
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (L.C.); (K.W.); (J.L.); (Y.L.)
| | - Huiqing Cao
- Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100084, China
| | - Zhe Zheng
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China & Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (L.C.); (K.W.); (J.L.); (Y.L.)
- National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Central-China Branch of National Center for Cardiovascular Diseases, Fuwai Central-China Hospital, Beijing 100037, China
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Oncogenic role and potential regulatory mechanism of topoisomerase IIα in a pan-cancer analysis. Sci Rep 2022; 12:11161. [PMID: 35778520 PMCID: PMC9249858 DOI: 10.1038/s41598-022-15205-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 06/20/2022] [Indexed: 11/08/2022] Open
Abstract
Topoisomerase IIα (TOP2A) plays an oncogenic role in multiple tumor types. However, no pan-cancer analysis about the function and the upstream molecular mechanism of TOP2A is available. For the first time, we analyzed potential oncogenic roles of TOP2A in 33 cancer types via The Cancer Genome Atlas (TCGA) database. Overexpression of TOP2A was existed in almost all cancer types, and related to poor prognosis and advanced pathological stages in most cases. Besides, the high frequency of TOP2A genetic alterations was observed in several cancer types, and related to prognosis in some cases. Moreover, we conduct upstream miRNAs and lncRNAs of TOP2A to establish ceRNA networks in kidney renal clear cell carcinoma (SNHG3-miR-139-5p), kidney renal papillary cell carcinoma (TMEM147-AS1/N4BP2L2-IT2/THUMPD3-AS1/ERICD/TTN-AS1/SH3BP5-AS1/THRB-IT1/SNHG3/NEAT1-miR-139-5p), liver hepatocellular carcinoma (SNHG3/THUMPD3-AS1/NUTM2B-AS1/NUTM2A-AS1-miR-139-5p and SNHG6/GSEC/SNHG1/SNHG14/LINC00265/MIR3142HG-miR-101-3p) and lung adenocarcinoma (TYMSOS/HELLPAR/SNHG1/GSEC/SNHG6-miR-101-3p). TOP2A expression was generally positively correlated with cancer associated fibroblasts, M0 and M1 macrophages in most cancer types. Furthermore, TOP2A was positively associated with expression of immune checkpoints (CD274, CTLA4, HAVCR2, LAG3, PDCD1 and TIGIT) in most cancer types. Our first TOP2A pan-cancer study contributes to understanding the prognostic roles, immunological roles and potential upstream molecular mechanism of TOP2A in different cancers.
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Identification of m6A-Related lncRNA to Predict the Prognosis of Patients with Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4169150. [PMID: 35592519 PMCID: PMC9112178 DOI: 10.1155/2022/4169150] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 03/16/2022] [Accepted: 04/01/2022] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In the past decades, HCC treatment has achieved great progress; however, the overall prognosis remains poor. Therefore, it is the need of the hour to identify new prognostic biomarkers which can advance our understanding related to the underlying molecular mechanism of adverse prognosis and apply them to clinical work in prognosis prediction. In the present study, data of 576 HCC patients and 292 normal control cases from TCGA and ICGC databases were enrolled to our bioinformatic analysis. SNHG1 and SNHG3 were identified as overlapping genes in TCGA and ICGC databases using Pearson correlation analysis and univariate Cox regression analysis. Further, we used the median of the SNHG1 and SNHG3 expression values as the cutoff values to define the HCC patient groups with high or low expression level. The subsequent analysis revealed that abnormal high expression of SNHG1 or SNHG3 affected the immune infiltration patterns and the crosstalk among immune cells. Moreover, high expression of SNHG1 or SNHG3 resulted in drug resistant to AKT inhibitor VII, bexarotene, bicalutamide, dasatinib, erlotinib, and gefitinib. In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Further, we found significant relation between the aberrant upregulation of SNHG1 and SNHG3 in tumor grade and stage. We established a nomogram to systematically predict the 5- and 8-year overall survival of liver cancer patients with good accuracy. Finally, the in vitro assays suggest that SNHG1 and SNHG3 promote the proliferative, migratory, and invasive abilities of HCC cells.
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Shan DD, Zheng QX, Wang J, Chen Z. Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression. World J Gastroenterol 2022; 28:1641-1655. [PMID: 35581965 PMCID: PMC9048787 DOI: 10.3748/wjg.v28.i16.1641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/09/2022] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.
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Affiliation(s)
- Dan-Dan Shan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qiu-Xian Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Jing Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Bieńkiewicz J, Romanowicz H, Szymańska B, Domańska-Senderowska D, Wilczyński M, Stepowicz A, Malinowski A, Smolarz B. Analysis of lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 in endometrial cancer. BMC Cancer 2022; 22:343. [PMID: 35351056 PMCID: PMC8966281 DOI: 10.1186/s12885-022-09426-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/16/2022] [Indexed: 11/10/2022] Open
Abstract
Background The analysis of long non-coding RNA (lncRNA) in endometrial cancer is a novel field of science. Although numerous lncRNA sequences have been identified until today, their correlation with endometrial cancer is still undetermined. The aim of this study was to analyze the expression of four lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 and to investigate their significance in endometrial cancer. Methods LncRNA sequences were investigated in paraffin blocks (tumor tissue and non-malignant endometrial tissue in archival postoperative specimens) in endometrial cancer patients (Cases, n = 120) and in cancer-free controls (n = 80) using real-time PCR assay. Results This study revealed a lower expression of LINC01468 in endometrial cancer patients than in controls. Both LINC01468 and FAM3D-AS1 were positively correlated with Body Mass Index (BMI) in cancer-free controls. Conclusions LncRNA LINC01468 may be a protective factor in development of endometrial cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09426-2.
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Affiliation(s)
- Jan Bieńkiewicz
- Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother's Memorial Hospital - Research Institute, 281/289, Rzgowska Street, 93-338, Lodz, Poland.
| | - Hanna Romanowicz
- Department of Clinical Pathology, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland
| | - Bożena Szymańska
- Research Laboratory CoreLab, Medical University of Lodz, Lodz, Poland
| | | | - Miłosz Wilczyński
- Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother's Memorial Hospital - Research Institute, 281/289, Rzgowska Street, 93-338, Lodz, Poland
| | - Anna Stepowicz
- Department of Obstetrics, Perinatology and Gynecology, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland
| | - Andrzej Malinowski
- Department of Operative and Endoscopic Gynecology, Medical University of Lodz, Lodz, Poland
| | - Beata Smolarz
- Department of Clinical Pathology, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland
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Stavast CJ, van Zuijen I, Erkeland SJ. MicroRNA-139, an Emerging Gate-Keeper in Various Types of Cancer. Cells 2022; 11:cells11050769. [PMID: 35269391 PMCID: PMC8909004 DOI: 10.3390/cells11050769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 02/17/2022] [Accepted: 02/19/2022] [Indexed: 11/25/2022] Open
Abstract
Mounting data show that MIR139 is commonly silenced in solid cancer and hematological malignancies. MIR139 acts as a critical tumor suppressor by tuning the cellular response to different types of stress, including DNA damage, and by repressing oncogenic signaling pathways. Recently, novel insights into the mechanism of MIR139 silencing in tumor cells have been described. These include epigenetic silencing, inhibition of POL-II transcriptional activity on gene regulatory elements, enhanced expression of competing RNAs and post-transcriptional regulation by the microprocessor complex. Some of these MIR139-silencing mechanisms have been demonstrated in different types of cancer, suggesting that these are more general oncogenic events. Reactivation of MIR139 expression in tumor cells causes inhibition of tumor cell expansion and induction of cell death by the repression of oncogenic mRNA targets. In this review, we discuss the different aspects of MIR139 as a tumor suppressor gene and give an overview on different transcriptional mechanisms regulating MIR139 in oncogenic stress and across different types of cancer. The novel insights into the expression regulation and the tumor-suppressing activities of MIR139 may pave the way to new treatment options for cancer.
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Sun Z, Hu J, Ren W, Fang Y, Hu K, Yu H, Liao D, Liu S, Zhou L, He T, Zhang Y. LncRNA SNHG3 regulates the BMSC osteogenic differentiation in bone metastasis of breast cancer by modulating the miR-1273g-3p/BMP3 axis. Biochem Biophys Res Commun 2022; 594:117-123. [DOI: 10.1016/j.bbrc.2021.12.075] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 12/21/2021] [Indexed: 12/17/2022]
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A diagnostic and prognostic value of blood-based circulating long non-coding RNAs in Thyroid, Pancreatic and Ovarian Cancer. Crit Rev Oncol Hematol 2022; 171:103598. [PMID: 35033662 DOI: 10.1016/j.critrevonc.2022.103598] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 12/12/2022] Open
Abstract
Several studies have demonstrated the potential of circulating long non-coding RNAs (lncRNAs) as promising cancer biomarkers. Herein, we addressed the regulatory role of circulating lncRNAs and their potential value as diagnostic/prognostic markers for thyroid, pancreatic and ovarian cancers. Furthermore, we analyzed and measured the clinical implications and association of lncRNAs with sensitivity, specificity, and area under the ROC curve (AUC). Based on our meta-analysis, we found that GAS8-AS1 could discriminate thyroid cancer from non-cancer and other cancers with higher accuracy (AUC = 0.746; sensitivity = 61.70%, and specificity = 90.00%). Similarly, for ovarian cancer, lncRNA RP5-837J1.2 was found to have ideal diagnostic potential with critical clinical specifications of AUC = 0.996; sensitivity = 97.30% and specificity = 94.60%. Whereas we could not find any lncRNA having high diagnostic/prognostic efficiency in pancreatic cancer. We believe that lncRNAs mentioned above may explore clinical settings for the diagnosis and prognosis of cancer patients.
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Sun JY, Ni MM. Long non-coding RNA HEIH: a novel tumor activator in multiple cancers. Cancer Cell Int 2021; 21:558. [PMID: 34689775 PMCID: PMC8543845 DOI: 10.1186/s12935-021-02272-5] [Citation(s) in RCA: 7] [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: 08/04/2021] [Accepted: 10/16/2021] [Indexed: 12/27/2022] Open
Abstract
The last decade has witnessed the altered expression levels of long non-coding RNA HEIH in different types of cancer. More than half of the HEIH studies in cancer have been published within the last two years. To our knowledge, this is the first review to discuss very recent developments and insights into HEIH contribution to carcinogenesis. The functional role, molecular mechanism, and clinical significance of HEIH in human cancers are described in detail. The expression of HEIH is elevated in a broad spectrum of cancers, and its disorder contributes to cell proliferation, migration, invasion, and drug resistance of cancer cells through different underlying mechanisms. In addition, the high expression of HEIH is significantly associated with advanced tumor stage, tumor size and decreased overall survival, suggesting HEIH may function as a prognostic biomarker and potential therapeutic target for human cancers.
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Affiliation(s)
- Jie-Yu Sun
- Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China
| | - Ming-Ming Ni
- Department of Pharmacy, Children's Hospital of Nanjing Medical University, 72 Guangzhou Rd., Nanjing, 210008, People's Republic of China.
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