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Jiang J, Sun M, Wang Y, Huang W, Xia L. Deciphering the roles of the HMGB family in cancer: Insights from subcellular localization dynamics. Cytokine Growth Factor Rev 2024; 78:85-104. [PMID: 39019664 DOI: 10.1016/j.cytogfr.2024.07.004] [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: 06/03/2024] [Revised: 07/08/2024] [Accepted: 07/08/2024] [Indexed: 07/19/2024]
Abstract
The high-mobility group box (HMGB) family consists of four DNA-binding proteins that regulate chromatin structure and function. In addition to their intracellular functions, recent studies have revealed their involvement as extracellular damage-associated molecular patterns (DAMPs), contributing to immune responses and tumor development. The HMGB family promotes tumorigenesis by modulating multiple processes including proliferation, metabolic reprogramming, metastasis, immune evasion, and drug resistance. Due to the predominant focus on HMGB1 in the literature, little is known about the remaining members of this family. This review summarizes the structural, distributional, as well as functional similarities and distinctions among members of the HMGB family, followed by a comprehensive exploration of their roles in tumor development. We emphasize the distributional and functional hierarchy of the HMGB family at both the organizational and subcellular levels, with a focus on their relationship with the tumor immune microenvironment (TIME), aiming to prospect potential strategies for anticancer therapy.
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Affiliation(s)
- Junqing Jiang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, China
| | - Mengyu Sun
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, China
| | - Yufei Wang
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, China
| | - Wenjie Huang
- Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Clinical Medicine Research Center for Hepatic Surgery of Hubei Province, Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, Hubei 430030, China.
| | - Limin Xia
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, China; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi' an 710032, China.
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Bai S, Guo J, Zhang H. A meta-analysis of the clinicopathological significance of the lncRNA MALAT1 in human gastric cancer. Front Oncol 2024; 13:1257120. [PMID: 38239645 PMCID: PMC10794718 DOI: 10.3389/fonc.2023.1257120] [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: 07/12/2023] [Accepted: 11/22/2023] [Indexed: 01/22/2024] Open
Abstract
Background Dysregulation of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been linked to some oncogenic pathways that induce cancer initiation and progression. This meta-analysis was conducted to specifically summarize the most recent research on MALAT1 function in human gastric cancer (GC). Methods The eligible studies were first identified by searching HowNet, Web of Science, PubMed, The Cochrane Library, Embase, and Nature databases for studies published as of April 1, 2023. The meta-analysis included 14 studies assessing MALAT1 expression and presenting clinical parameters and survival outcomes. Results The results illustrated that high MALAT1 expression is predictive of lymph node metastasis (pooled odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.97-4.54, P < 0.001) and distant metastasis in GC (OR = 3.11, 95% CI = 1.68-5.75, P < 0.001). In addition, MALAT1 was associated with GC tumor invasion (T3/T4 vs. T1/T2: OR = 2.90, 95% CI = 1.90- 4.41, P <0.001) and TNM stage (III/IV vs I/II: OR = 2.93, 95% CI: 1.80-4.77, P <0.001). Additionally, higher MALAT-1 expression predicted poorer overall survival in patients with GC (hazard ratio = 1.64, 95% CI = 1.20-2.09, P < 0.001). Conclusions The current findings suggest that the high MALAT1 expression is an adverse biomarker for prognostic outcomes, lymph node metastasis, TNM stage, and distant metastasis in GC and MALAT1 could be a prognostic biomarker for GC.
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Affiliation(s)
- Shaoxiong Bai
- Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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Syllaios A, Gazouli M, Vailas M, Mylonas KS, Sakellariou S, Sougioultzis S, Karavokyros I, Liakakos T, Schizas D. The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma. Int J Mol Sci 2023; 25:98. [PMID: 38203269 PMCID: PMC10778904 DOI: 10.3390/ijms25010098] [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: 10/18/2023] [Revised: 12/09/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.
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Affiliation(s)
- Athanasios Syllaios
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | - Maria Gazouli
- Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Michail Vailas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | | | - Stratigoula Sakellariou
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Stavros Sougioultzis
- Gastroenterology Unit, Department of Pathophysiology, School of Medicine, National and Kapodistrian University Athens, 115 27 Athens, Greece;
| | - Ioannis Karavokyros
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | - Theodoros Liakakos
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece; (M.V.); (I.K.); (T.L.); (D.S.)
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Ebrahimi N, Hakimzadeh A, Bozorgmand F, Speed S, Manavi MS, Khorram R, Farahani K, Rezaei-Tazangi F, Mansouri A, Hamblin MR, Aref AR. Role of non-coding RNAs as new therapeutic targets in regulating the EMT and apoptosis in metastatic gastric and colorectal cancers. Cell Cycle 2023; 22:2302-2323. [PMID: 38009668 PMCID: PMC10730205 DOI: 10.1080/15384101.2023.2286804] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 05/11/2023] [Accepted: 08/01/2023] [Indexed: 11/29/2023] Open
Abstract
Colorectal cancer (CRC) and gastric cancer (GC), are the two most common cancers of the gastrointestinal tract, and are serious health concerns worldwide. The discovery of more effective biomarkers for early diagnosis, and improved patient prognosis is important. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can regulate cellular processes such as apoptosis and the epithelial-mesenchymal transition (EMT) leading to progression and resistance of GC and CRC tumors. Moreover these pathways (apoptosis and EMT) may serve as therapeutic targets, to prevent metastasis, and to overcome drug resistance. A subgroup of ncRNAs is common to both GC and CRC tumors, suggesting that they might be used as biomarkers or therapeutic targets. In this review, we highlight some ncRNAs that can regulate EMT and apoptosis as two opposite mechanisms in cancer progression and metastasis in GC and CRC. A better understanding of the biological role of ncRNAs could open up new avenues for the development of personalized treatment plans for GC and CRC patients.
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Affiliation(s)
- Nasim Ebrahimi
- Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
| | - Ali Hakimzadeh
- Department of Medical Biotechnologies, University of Siena, Tuscany, Italy
| | - Farima Bozorgmand
- Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Sepehr Speed
- Medical Campus, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | | | - Roya Khorram
- Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kobra Farahani
- Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Fatemeh Rezaei-Tazangi
- Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Atena Mansouri
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Reza Aref
- Xsphera Biosciences, Translational Medicine group, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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Batista DMDO, da Silva JMC, Gigek CDO, Smith MDAC, de Assumpção PP, Calcagno DQ. Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression. World J Gastrointest Oncol 2023; 15:1520-1530. [PMID: 37746646 PMCID: PMC10514724 DOI: 10.4251/wjgo.v15.i9.1520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/30/2023] [Accepted: 07/27/2023] [Indexed: 09/13/2023] Open
Abstract
Gastric cancer (GC) remains among the most common cancers worldwide with a high mortality-to-incidence ratio. Accumulated evidence suggests that long noncoding RNAs (lncRNAs) are involved in gastric carcinogenesis. These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels, inducing or inhibiting biological processes and diseases. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression. This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins. In the present review, we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC. Moreover, we highlighted the potential use of MALAT1 as a biomarker, including liquid biopsy.
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Affiliation(s)
| | | | | | - Marília de Arruda Cardoso Smith
- Disciplina de Genética,Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo 04023-900, São Paulo, Brazil
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Wu Z, Huang Y, Yuan W, Wu X, Shi H, Lu M, Xu A. Expression, tumor immune infiltration, and prognostic impact of HMGs in gastric cancer. Front Oncol 2022; 12:1056917. [PMID: 36568211 PMCID: PMC9780705 DOI: 10.3389/fonc.2022.1056917] [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: 09/29/2022] [Accepted: 11/07/2022] [Indexed: 12/13/2022] Open
Abstract
Background In the past decade, considerable research efforts on gastric cancer (GC) have been expended, however, little advancement has been made owing to the lack of effective biomarkers and treatment options. Herein, we aimed to examine the levels of expression, mutations, and clinical relevance of HMGs in GC to provide sufficient scientific evidence for clinical decision-making and risk management. Methods GC samples were obtained from The Cancer Genome Atlas (TCGA). University of California Santa Cruz (UCSC) XENA, Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, LinkedOmics, and DAVID databases were employed. The "ggplot2" package in the R software (×64 3.6.3) was used to thoroughly analyze the effects of HMGs. qRT-PCR was performed to assess HMG levels in GC cell lines. Results A total of 375 GC tissues and 32 paraneoplastic tissues were analyzed. The levels of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN1, HMGN2, and HMGN4 expression were increased in GC tissues relative to normal gastric tissues. HMGA1, HMGA2, HMGB1, HMGB2, and HMGB3 were highly expressed in GC cell lines. The OS was significantly different in the group showing low expressions of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN2, HMGN3, and HMGN5. There was a significant difference in RFS between the groups with low HMGA2, HMGB3, and high HMGN2 expression. The levels of HMGA2, HMGB3, and HMGN1 had a higher accuracy for prediction to distinguish GC from normal tissues (AUC value > 0.9). HMGs were tightly associated with immune infiltration and tumor immune escape and antitumor immunity most likely participates in HMG-mediated oncogenesis in GC. GO and KEGG enrichment analyses showed that HMGs played a vital role in the cell cycle pathway. Conclusions Our results strongly suggest a vital role of HMGs in GC. HMGA2 and HMGB3 could be potential markers for prognostic prediction and treatment targets for GC by interrupting the cell cycle pathway. Our findings might provide renewed perspectives for the selection of prognostic biomarkers among HMGs in GC and may contribute to the determination of the optimal strategy for the treatment of these patients.
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Affiliation(s)
- Zhiheng Wu
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China,Department of General Surgery, Anhui Public Health Clinical Center, Hefei, Anhui, China
| | - Yang Huang
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China,Department of General Surgery, Anhui Public Health Clinical Center, Hefei, Anhui, China
| | - Weiwei Yuan
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China,Department of General Surgery, Anhui Public Health Clinical Center, Hefei, Anhui, China
| | - Xiong Wu
- School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical University, PR China, State Key Laboratory of Optometry, Ophthalmology, and Visual Science, Wenzhou, Zhejiang, China
| | - Hui Shi
- Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
| | - Ming Lu
- Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
| | - Aman Xu
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China,Department of General Surgery, Anhui Public Health Clinical Center, Hefei, Anhui, China
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KIM EOJIN, KIM HYUNJIN, YEO MINKYUNG, KIM CHULHWAN, KIM JOOYOUNG, PARK SUNGSOO, KIM HYUNSOO, CHAE YANGSEOK. Identification of a Novel Long Non-coding RNA, lnc-ATMIN-4:2, and its Clinicopathological and Prognostic Significance in Advanced Gastric Cancer. Cancer Genomics Proteomics 2022; 19:761-772. [PMID: 36316044 PMCID: PMC9620448 DOI: 10.21873/cgp.20358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/21/2022] [Accepted: 09/26/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND/AIM Long non-coding RNAs (lncRNAs) are emerging as significant regulators of gene expression and a novel promising biomarker for cancer diagnosis and prognosis. This study identified a novel, differentially expressed lncRNA in advanced gastric cancer (AGC), Inc-ATMIN-4:2, and evaluated its clinicopathological and prognostic significance. PATIENTS AND METHODS Whole transcriptome sequencing was performed to identify differentially expressed lncRNAs in AGC tissue samples. We also analyzed lnc-ATMIN-4:2 expression in 317 patients with AGC using RNA in situ hybridization. RESULTS High (>30 dots) lnc-ATMIN-4:2 expression significantly correlated with younger age, poorly differentiated histology, diffuse type, deeper invasion depth, perineural invasion, lymph node metastasis, and higher stage group. In addition, high lnc-ATMIN-4:2 expression was significantly associated with worse overall survival in patients with AGC. CONCLUSION This study elucidated the significance of lncRNAs in AGC and indicated the value of lnc-ATMIN-4:2 expression as a predictive biomarker for the overall survival of patients with AGC.
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Affiliation(s)
- EOJIN KIM
- Department of Pathology, Korea University College of Medicine, Seoul, Republic of Korea
| | - HYUNJIN KIM
- Pathology Center, Seegene Medical Foundation, Seoul, Republic of Korea
| | - MIN-KYUNG YEO
- Department of Pathology, Chungnam National University School of Medicine, Daejeon, Republic of Korea
| | - CHUL HWAN KIM
- Department of Pathology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - JOO YOUNG KIM
- Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - SUNGSOO PARK
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - HYUN-SOO KIM
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - YANG-SEOK CHAE
- Department of Pathology, Korea University College of Medicine, Seoul, Republic of Korea,Department of Pathology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Feng YN, Li BY, Wang K, Li XX, Zhang L, Dong XZ. Epithelial-mesenchymal transition-related long noncoding RNAs in gastric carcinoma. Front Mol Biosci 2022; 9:977280. [PMCID: PMC9605205 DOI: 10.3389/fmolb.2022.977280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022] Open
Abstract
As an evolutionarily phenotypic conversion program, the epithelial-mesenchymal transition (EMT) has been implicated in tumour deterioration and has facilitated the metastatic ability of cancer cells via enhancing migration and invasion. Gastric cancer (GC) remains a frequently diagnosed non-skin malignancy globally. Most GC-associated mortality can be attributed to metastasis. Recent studies have shown that EMT-related long non-coding RNAs (lncRNAs) play a critical role in GC progression and GC cell motility. In addition, lncRNAs are associated with EMT-related transcription factors and signalling pathways. In the present review, we comprehensively described the EMT-inducing lncRNA molecular mechanisms and functional perspectives of EMT-inducing lncRNAs in GC progression. Taken together, the statements of this review provided a clinical implementation in identifying lncRNAs as potential therapeutic targets for advanced GC.
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Qiu X, Liu W, Zheng Y, Zeng K, Wang H, Sun H, Dai J. Identification of HMGB2 associated with proliferation, invasion and prognosis in lung adenocarcinoma via weighted gene co-expression network analysis. BMC Pulm Med 2022; 22:310. [PMID: 35962344 PMCID: PMC9373369 DOI: 10.1186/s12890-022-02110-y] [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: 04/26/2022] [Accepted: 08/09/2022] [Indexed: 11/25/2022] Open
Abstract
Background High mobility group protein B2 (HMGB2) is a multifunctional protein that plays various roles in different cellular compartments. Moreover, HMGB2 serves as a potential prognostic biomarker and therapeutic target for lung adenocarcinoma (LUAD). Methods In this study, the expression pattern, prognostic implication, and potential role of HMGB2 in LUAD were evaluated using the integrated bioinformatics analyses based on public available mRNA expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, both at the single-cell level and the tissue level. Further study in the patient-derived samples was conducted to explore the correlation between HMGB2 protein expression levels with tissue specificity, (tumor size-lymph node-metastasis) TNM stage, pathological grade, Ki-67 status, and overall survival. In vitro experiments, such as CCK-8, colony-formation and Transwell assay, were performed with human LUAD cell line A549 to investigate the role of HMGB2 in LUAD progression. Furthermore, xenograft tumor model was generated with A549 in nude mice. Results The results showed that the HMGB2 expression was higher in the LUAD samples than in the adjacent normal tissues and was correlated with high degree of malignancy in different public data in this study. Besides, over-expression of HMGB2 promoted A549 cells proliferation and migration while knocking down of HMGB2 suppressed the tumor promoting effect. Conclusions Our study indicated that HMGB2 was remarkably highly expressed in LUAD tissues, suggesting that it is a promising diagnostic and therapeutic marker for LUAD in the future. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-02110-y.
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Affiliation(s)
- Xie Qiu
- Department of Cardiothoracic Surgery, The First People's Hospital of Lianyungang, Lianyungang, People's Republic of China
| | - Wei Liu
- Department of Thoracic Surgery, Haian People's Hospital Affiliated to Nantong University, Haian, People's Republic of China
| | - Yifan Zheng
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nantong University, Nantong, People's Republic of China
| | - Kai Zeng
- Department of Thyroid Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518000, China
| | - Hao Wang
- Yancheng TCM Hospital, Nanjing University of Chinese Medicine, Yancheng, 224002, China
| | - Haijun Sun
- Department of Cardiothoracic Surgery, The First People's Hospital of Lianyungang, Lianyungang, People's Republic of China.
| | - Jianhua Dai
- Department of Cardiothoracic Surgery, The First People's Hospital of Lianyungang, Lianyungang, People's Republic of China.
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10
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Jiang P, Mao L, Lei X, Luo C, Zhang Y, Zhong X, Yin Z, Xu X, Li D, Zheng Q. miR-1297 inhibits osteosarcoma cell proliferation and growth by targeting CCND2. Am J Cancer Res 2022; 12:3464-3478. [PMID: 35968334 PMCID: PMC9360223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/02/2022] [Indexed: 06/15/2023] Open
Abstract
Cyclin D2 (CCND2) is abnormally overexpressed in many tumor types and has been associated with tumor cell proliferation. Although the important role of miR-1297 is well established, the molecular mechanism between CCND2 and miR-1297 in osteosarcoma (OS) has not been determined. In the present study, we found CCND2 was highly expressed in OS cells, and its downregulation suppressed cell proliferation, resulting in G1 phase cell cycle arrest. In contrast, miR-1297 was lowly expressed in OS compared to normal tissue. Several data platforms predicted that CCND2 was a target of miR-1297, which was validated by a dual-luciferase reporter assay that revealed miR-1297 could bind with CCND2-3'UTR. miR-1297 overexpression greatly inhibited CCND2 protein expression and exerted the same phenotypic effect as CCND2 downregulation in OS cells. Furthermore, miR-1297 inhibition could also be rescued by CCND2. Nude mice injected cells stable overexpressing miR-1297 OS cells showed lower size and tumor weight. Moreover, lower fluorescence activity recorded by in vivo imaging system and bone erosion revealed by microCT in the miR-1297 group demonstrated miR-1297 inhibited OS tumor growth via CCND2. Our findings demonstrated that miR-1297 can inhibit proliferation and tumor growth in OS by directly targeting CCND2, which indicates that miR-1297 may represent a novel therapeutic target for OS.
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Affiliation(s)
- Pan Jiang
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
- Guizhou Orthopedics HospitalGuizhou, China
| | - Lianghao Mao
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
| | - Xuan Lei
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
| | | | - Yiming Zhang
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
| | - Xinyu Zhong
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
| | - Zhenyu Yin
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
| | - Xiaofeng Xu
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
| | - Dapeng Li
- Affiliated Hospital of Jiangsu UniversityZhenjiang, China
| | - Qiping Zheng
- Department of Laboratory Science, School of Medicine, Jiangsu UniversityZhenjiang, China
- Shenzhen Walgenron Bio-Pharm Co., Ltd.Shenzhen 518118, Guangdong, China
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11
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Yang Z, Xia L. Resveratrol inhibits the proliferation, invasion, and migration, and induces the apoptosis of human gastric cancer cells through the MALAT1/miR-383-5p/DDIT4 signaling pathway. J Gastrointest Oncol 2022; 13:985-996. [PMID: 35837196 DOI: 10.21037/jgo-22-307] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/27/2022] [Indexed: 11/06/2022] Open
Abstract
Background We aimed to study the effects and potential mechanism of resveratrol (RS) in gastric cancer (GC). Methods The human GC cell line SGC7901 was treated with different concentrations of RS (0, 1, 5 µM) for 24 hours. The messenger ribonucleic acid or protein expressions levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), micro ribonucleic acid-383-5p (miR-383-5p), and DNA damage-inducible transcript 4 (DDIT4) in GC cells were determined by Western blot and quantitative real-time polymerase chain assays. Cells were then transfected with miR-383-5p inhibitor (inhibitor), inhibitor negative control (NC), MALAT1-interfering RNA (si-MALAT1), si-DDIT4 and negative interference control (si-NC). The Cell Counting Kit-8 method, scratch assay, and transwell assay were performed to evaluate cell proliferation, migration, and invasion. Additionally, flow cytometry was used to examine apoptosis, and the target relationship was examined by a luciferase-reporter gene analysis. Results RS treatment downregulated the expression of MALAT1, repressed cell proliferation, inhibited cell migration and invasion (all P<0.05), and induced apoptosis (P<0.05) in GC cells. When the cells were treated with RS and inhibited the expression of MALAT1 meanwhile, the above anti-cancer effects were more significant (all P<0.05). Target prediction and the luciferase-reporter gene analysis showed that MALAT1 targeted miR-383-5p (P<0.05). When suppressing the expression of MALAT1 and miR-383-5p, the anti-cancer effects caused by the silencing of MALAT1 were absent (all P<0.05). We also found that miR-383-5p targeted DDIT4 protein. When the expression of miR-383-5p and DDIT4 in the GC cells was inhibited, the promoting cancer effects caused by the inhibition of miR-383-5p were reversed (all P<0.05). Conclusions This study found that RS inhibited the proliferation, migration, and invasion of human GC cells through the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-383-5p/DDIT4 pathway and induced apoptosis.
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Affiliation(s)
- Zhuying Yang
- Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Liang Xia
- Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China
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Mei J, Liu G, Li R, Xiao P, Yang D, Bai H, Hao Y. LncRNA SNHG6 knockdown inhibits cisplatin resistance and progression of gastric cancer through miR-1297/BCL-2 axis. Biosci Rep 2021; 41:BSR20211885. [PMID: 34821362 PMCID: PMC8661508 DOI: 10.1042/bsr20211885] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 11/11/2021] [Accepted: 11/15/2021] [Indexed: 12/11/2022] Open
Abstract
Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelial-mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were up-regulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment.
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Affiliation(s)
- Jiazhuan Mei
- Department of Oncology, People’s Hospital of Zhengzhou Affiliated to Southern Medical University, Zhengzhou, Henan, China
| | - Guiju Liu
- Department of Oncology, People’s Hospital of Zhengzhou Affiliated to Southern Medical University, Zhengzhou, Henan, China
| | - Ruijun Li
- Department of Oncology, People’s Hospital of Zhengzhou Affiliated to Southern Medical University, Zhengzhou, Henan, China
| | - Peng Xiao
- Department of Oncology, People’s Hospital of Zhengzhou Affiliated to Southern Medical University, Zhengzhou, Henan, China
| | - Dan Yang
- Department of Oncology, People’s Hospital of Zhengzhou Affiliated to Southern Medical University, Zhengzhou, Henan, China
| | - Hua Bai
- Department of Oncology, People’s Hospital of Zhengzhou Affiliated to Southern Medical University, Zhengzhou, Henan, China
| | - Yibin Hao
- Department of Oncology, People’s Hospital of Zhengzhou Affiliated to Southern Medical University, Zhengzhou, Henan, China
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Wang Y, Liu X, Wang L, Zhang Z, Li Z, Li M. Circ_PGPEP1 Serves as a Sponge of miR-1297 to Promote Gastric Cancer Progression via Regulating E2F3. Dig Dis Sci 2021; 66:4302-4313. [PMID: 33386518 DOI: 10.1007/s10620-020-06783-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 12/11/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Circular RNA (circRNA) is a special kind of noncoding RNA that plays a vital function in the progression of gastric cancer (GC). However, the role of a new circRNA, circ_PGPEP1, in GC is unclear. AIMS Exploring the role and mechanism of circ_PGPEP1 in GC progression. METHODS The expression levels of circ_PGPEP1, miR-1297, and E2F transcription factor 3 (E2F3) were determined using quantitative real-time PCR. Flow cytometry, colony formation assay, MTT assay, and transwell assay were used to evaluate cell cycle, apoptosis, proliferation, migration, and invasion. The protein levels of apoptosis-related markers and E2F3 were measured by western blot analysis. The interaction between circ_PGPEP1 and miR-1297 or miR-1297 and E2F3 was confirmed by dual-luciferase reporter assay. In addition, animal experiments were performed to assess the effect of circ_PGPEP1 on GC tumor growth in vivo. RESULTS Circ_PGPEP1 was a highly expressed circRNA in GC. Loss-of-function experiment indicated that circ_PGPEP1 silencing could induce cell cycle arrest and apoptosis, while inhibit proliferation, migration, and invasion in GC cells. MiR-1297 could be sponged by circ_PGPEP1, and its expression was downregulated in GC. MiR-1297 inhibitor could reverse the negatively regulation of circ_PGPEP1 knockdown on GC progression. Furthermore, we also found that E2F3 could be targeted by miR-1297, and its expression was positively regulated by circ_PGPEP1. Overexpression of E2F3 could invert the inhibitory effect of miR-1297 on GC progression. Animal experiments suggested that silenced circ_PGPEP1 could reduce GC tumor growth. CONCLUSION Our research showed that circ_PGPEP1 might serve as a potential biomarker for GC.
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Affiliation(s)
- Yingxin Wang
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Xia Liu
- Department of Forensic Pathology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Liwei Wang
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Zhenduo Zhang
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Zhong Li
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China
| | - Ming Li
- Department of General Surgery, Shijiazhuang People's Hospital, No. 365 Jianhuanan Street, Shijiazhuang, 050031, Hebei, China.
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Wang W, Li L, Zhao L. LINC00184 plays an oncogenic role in non-small cell lung cancer via regulation of the miR-524-5p/HMGB2 axis. J Cell Mol Med 2021; 25:9927-9938. [PMID: 34651416 PMCID: PMC8572802 DOI: 10.1111/jcmm.16247] [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: 02/25/2020] [Revised: 11/19/2020] [Accepted: 12/03/2020] [Indexed: 12/13/2022] Open
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. We aimed to investigate the role of LINC00184 in NSCLC. Migration, proliferation and invasion of NSCLC cells were analysed using the wound healing assay, cell counting kit-8 assay and transwell assay, respectively. Apoptosis and cell cycle were assessed using flow cytometry. Online bioinformatics tools were utilized to predict downstream microRNAs (miRNA) or genes related to LINC00184 expression. The RNA pull-down experiment and luciferase reporter assay were performed to verify the predictions thereof. LINC00184, miR-524-5p, and high mobility group 2 protein (HMGB2) expression levels in NSCLC tissues and cell lines were detected using quantitative real-time polymerase chain reaction. An NSCLC mouse model was constructed for in vivo experiments. LINC00184 overexpression was observed in NSCLC tissues and cell lines and was found to be correlated with poor prognosis. LINC00184 knockdown inhibited cell proliferation, migration and invasion, induced cell cycle arrest and accelerated apoptosis in NSCLC cell lines. LINC00184 suppressed tumour growth and proliferation in NSCLC mouse models and directly targeted the miR-524-5p/HMGB2 axis. Moreover, the expression levels of LINC00184 and HMGB2 were negatively correlated with miR-524-5p expression, whereas LINC00184 expression was positively correlated with HMGB2 expression. LINC00184 affected the cell cycle, proliferation, apoptosis, migration and invasion in NSCLC via regulation of the miR-524-5p/HMGB2 axis.
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Affiliation(s)
- Wuming Wang
- Department of Thoracic Surgery, Jiangxi Provincial Chest Hospital, Nanchang, China
| | - Lin Li
- Department of Thoracic Surgery, Ji'an Central People's Hospital, Ji'an, China
| | - Long Zhao
- Department of Thoracic Surgery, Jiangxi Provincial Chest Hospital, Nanchang, China
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Alizadeh-Fanalou S, Khosravi M, Alian F, Rokhsartalb-Azar S, Nazarizadeh A, Karimi-Dehkordi M, Mohammadi F. Dual role of microRNA-1297 in the suppression and progression of human malignancies. Biomed Pharmacother 2021; 141:111863. [PMID: 34243098 DOI: 10.1016/j.biopha.2021.111863] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/21/2021] [Accepted: 06/28/2021] [Indexed: 02/07/2023] Open
Abstract
MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded and tiny RNAs that modulate several biological functions, more importantly, the pathophysiology of numerous human cancers. They are bound with target mRNAs and thereby regulate gene expression at post-transcriptional levels. MiRNAs can either trigger cancer progression as an oncogene or alleviate it as a tumor suppressor. Abnormal expression of microRNA-1297 (miR-1297) has been noticed in several human cancers suggesting a distinct role for the miRNA in tumorigenesis. More specifically, it is both up-regulated and down-regulated in various cancers suggesting that it can act as both tumor suppressor and oncogene. This review systematically highlights the different roles of miR-1297 in the pathophysiology of human cancers, explains the mechanisms underlying miR-1297-mediated tumorigenesis, and discusses its potential prognostic, diagnostic, and therapeutic importance.
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Affiliation(s)
- Shahin Alizadeh-Fanalou
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Khosravi
- Department of Biochemistry, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Fatemeh Alian
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Shirin Rokhsartalb-Azar
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University (TMU), Tehran, Iran
| | - Ali Nazarizadeh
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Karimi-Dehkordi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
| | - Forogh Mohammadi
- Department of Veterinary, Agriculture Faculty, Kermanshah branch, Islamic Azad University, Kermanshah, Iran.
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Ye J, Li J, Zhao P. Roles of ncRNAs as ceRNAs in Gastric Cancer. Genes (Basel) 2021; 12:genes12071036. [PMID: 34356052 PMCID: PMC8305186 DOI: 10.3390/genes12071036] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/28/2021] [Accepted: 06/28/2021] [Indexed: 01/19/2023] Open
Abstract
Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.
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Affiliation(s)
- Junhong Ye
- State Key Laboratory of Silkworm Genome Biology, Biological Science Research Center, Southwest University, Chongqing 400716, China;
| | - Jifu Li
- College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400716, China;
| | - Ping Zhao
- State Key Laboratory of Silkworm Genome Biology, Biological Science Research Center, Southwest University, Chongqing 400716, China;
- Correspondence: ; Tel.: +86-23-6825-0885
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The LncRNA RP11-301G19.1/miR-582-5p/HMGB2 axis modulates the proliferation and apoptosis of multiple myeloma cancer cells via the PI3K/AKT signalling pathway. Cancer Gene Ther 2021; 29:292-303. [PMID: 33707625 DOI: 10.1038/s41417-021-00309-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 01/26/2021] [Accepted: 02/05/2021] [Indexed: 12/15/2022]
Abstract
Long non-coding RNAs (lncRNAs) have recently been reported to act as crucial regulators and prognostic biomarkers of human tumorigenesis. Based on microarray data, RP11-301G19.1 was previously identified as an upregulated lncRNA during B cell development. However, the effect of RP11-301G19.1 on multiple myeloma (MM) cells remains unclear. In the present study, the effects of RP11-301G19.1 on tumour progression were ascertained both in vitro and in vivo. Our results demonstrated that RP11-301G19.1 was upregulated in MM cell lines and that its downregulation inhibited the proliferation and cell cycle progression and promoted the apoptosis of MM cells. Bioinformatic analysis and luciferase reporter assay results revealed that RP11-301G19.1 can upregulate the miR-582-5p-targeted gene HMGB2 as a competing endogenous RNA (ceRNA). Furthermore, Western blot results indicated that RP11-301G19.1 knockdown decreased the levels of PI3K and AKT phosphorylation without affecting their total protein levels. Additionally, in a xenograft model of human MM, RP11-301G19.1 knockdown significantly inhibited tumour growth by downregulating HMGB2. Overall, our data demonstrated that RP11-301G19.1 is involved in MM cell proliferation by sponging miR-582-5p and may serve as a therapeutic target for MM.
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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 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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Wang J, Wang F, Li Q, Wang Q, Li J, Wang Y, Sun J, Lu D, Zhou H, Li S, Ma S, Xie J, Wen T. Proteomics and molecular network analyses reveal that the interaction between the TAT-DCF1 peptide and TAF6 induces an antitumor effect in glioma cells. Mol Omics 2021; 16:73-82. [PMID: 31899468 DOI: 10.1039/c9mo00068b] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Glioblastoma is the most lethal brain cancer in adults. Despite advances in surgical techniques, radiotherapy, and chemotherapy, their therapeutic effect is far from significant, since the detailed underlying pathological mechanism of this cancer is unclear. The establishment of molecular interaction networks has laid the foundation for the exploration of these mechanisms with a view to improving therapy for glioblastoma. In the present study, to further explore the cellular role of DCF1 (dendritic cell-derived factor 1), the proteins bound to TAT-DCF1 (transactivator of transcription-dendritic cell-derived factor 1) were identified, and biosystem analysis was employed. Functional enrichment analyses indicate that TAT-DCF1 induced important biological changes in U251 cells. Furthermore, the established molecular interaction networks indicated that TAT-DCF1 directly interacted with TAF6 in glioma cells and with UBC in HEK293T (human embryonic kidney 293T) cells. In addition, further biological experiments demonstrate that TAT-DCF1 induced the activation of the RPS27A/TOP2A/HMGB2/BCL-2 signaling pathway via interaction with TAF6 in U251 cells. Taken together, these findings suggest that the TAT-DCF1 peptide possesses great potential for the development of glioblastoma therapy through the interaction with TAF6-related pathways and provides further theoretic evidence for the mechanisms underlying the antitumor effects of TAT-DCF1.
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Affiliation(s)
- Jiao Wang
- Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, 99 Shang Da Road, Shanghai 200444, China.
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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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Chaleshi V, Asadzadeh Aghdaei H, Nourian M, Iravani S, Jalaeikhoo H, Rajaeinejad M, Khoshdel AR, Naghoosi H. Association of MALAT1 expression in gastric carcinoma and the significance of its clinicopathologic features in an Iranian patient. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2021; 14:108-114. [PMID: 33968337 PMCID: PMC8101524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 08/29/2020] [Indexed: 02/08/2023]
Abstract
AIM The aim of this study was to evaluate the expression of MALAT1 and the relationship between its expression with clinical characteristics in an Iranian gastric cancer patient. BACKGROUND Long non-coding RNAs (LncRNAs) play critical roles in the initiation and development of gastric cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved lncRNA and plays key roles in various types of human cancer. However, our understanding of the role of lncRNAs in the occurrence and development of gastric cancer is not fully clear. METHODS This cross-sectional study was performed on 41 gastric tumor tissue samples with matched normal adjacent tumor tissues. The RNA level of lncRNA MALAT1 gene was assessed using quantitative Real-time polymerase chain reaction. B2M was used as an internal control. The 2 -ΔΔCq method was adopted to determine expression fold changes. RESULTS A significant association was observed between the levels of MALAT1 in gastric tumor tissues compared with normal adjacent tissues (mean= 1.558, p= 0.014). In addition, clinicopathologic data on MALAT1 RNA expression levels in gastric cancer tissues was evaluated. No significant association was observed between the relative expression of MALAT1 and the stage, grade, H. pylori infection, and tumor size groups among gastric cancer patients (p= 0.82, p= 0.904, p= 0.407, and p= 0.701, respectively). CONCLUSION The current results showed that MALAT1 has a significant association in gastric cancer. The expression of MALAT1 may be used as a diagnostic biomarker for monitoring gastric cancer patients.
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Affiliation(s)
- Vahid Chaleshi
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahyar Nourian
- Mahak Hematology Oncology Research Center (Mahak-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrokh Iravani
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Hasan Jalaeikhoo
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Mohsen Rajaeinejad
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Ali Reza Khoshdel
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
| | - Hamed Naghoosi
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran.
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Fu S, Wang Y, Li H, Chen L, Liu Q. Regulatory Networks of LncRNA MALAT-1 in Cancer. Cancer Manag Res 2020; 12:10181-10198. [PMID: 33116873 PMCID: PMC7575067 DOI: 10.2147/cmar.s276022] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 10/03/2020] [Indexed: 12/18/2022] Open
Abstract
Long noncoding (lnc)RNAs are a group of RNAs with a length greater than 200 nt that do not encode a protein but play an essential role in regulating the expression of target genes in normal biological contexts as well as pathologic processes including tumorigenesis. The lncRNA metastasis-associated lung adenocarcinoma transcript (MALAT)-1 has been widely studied in cancer. In this review, we describe the known functions of MALAT-1; its mechanisms of action; and associated signaling pathways and their clinical significance in different cancers. In most malignancies, including lung, colorectal, thyroid, and other cancers, MALAT-1 functions as an oncogene and is upregulated in tumors and tumor cell lines. MALAT-1 has a distinct mechanism of action in each cancer type and is thus at the center of large gene regulatory networks. Dysregulation of MALAT-1 affects cellular processes such as alternative splicing, epithelial–mesenchymal transition, apoptosis, and autophagy, which ultimately results in the abnormal cell proliferation, invasion, and migration that characterize cancers. In other malignancies, such as glioma and endometrial carcinoma, MALAT-1 functions as a tumor suppressor and thus forms additional regulatory networks. The current evidence indicates that MALAT-1 and its associated signaling pathways can serve as diagnostic or prognostic biomarker or therapeutic target in the treatment of many cancers.
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Affiliation(s)
- Shijian Fu
- The First Affiliated Hospital of Harbin Medical University, Harbin 150081, People's Republic of China
| | - Yanhong Wang
- Department of Laboratory Medicine, Yuebei People's Hospital of Shaoguan, The Affiliated Hospital of Shantou University, Shaoguan 512025, People's Republic of China
| | - Hang Li
- The First Affiliated Hospital of Harbin Medical University, Harbin 150081, People's Republic of China
| | - Leilei Chen
- Department of Cardiology, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing 100029, People's Republic of China
| | - Quanzhong Liu
- Department of Medical Genetics, Harbin Medical University, Harbin 150081, People's Republic of China
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Long noncoding RNA PART1 restrains aggressive gastric cancer through the epigenetic silencing of PDGFB via the PLZF-mediated recruitment of EZH2. Oncogene 2020; 39:6513-6528. [PMID: 32901105 DOI: 10.1038/s41388-020-01442-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 07/19/2020] [Accepted: 08/21/2020] [Indexed: 01/26/2023]
Abstract
Current reports refer to the role of long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) as a tumor suppressor in some types of cancer but as an oncogene in other kinds of cancer. In gastric cancer, it had been reported to be downregulated. However, the clinical significance and underlying mechanism of PART1 function in gastric cancer remains undefined. Here, seven differential expression levels of noncoding RNAs (DE-lncRNAs) were screened from gastric cancer through a probe reannotation of a human exon array. PART1 was selected for further study because of its high fold change number. In our cohort, PART1 was identified as a significant downregulated lncRNA in gastric cancer tissues by qPCR and in situ hybridization (ISH), and its low expression was significantly correlated with postoperative metastasis and short overall survival time after surgery. Through the results of gain-of-function experiments, PART1 was confirmed as a tumor suppressor that can decrease not only cell viability, migration, and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) showed that PART1 interacts with androgen receptor (AR), and then, promyelocytic leukemia zinc finger (PLZF) is upregulated in an androgen-independent manner. In a chain reaction, chromatin immunoprecipitation (ChIP) assay additionally illustrated that PLZF upregulation increased the enrichment of EZH2 and H3K27 trimethylation in the platelet-derived growth factor (PDGFB) promotor, thereby inhibition of PDGFB and the subsequent PDGFRβ/PI3K/Akt signaling pathway. Based on these findings, we showed PART1 plays a tumor suppressor role by promoting PLZF expression followed by recruitment of EZH2 to mediate epigenetic PDGFB silencing and downstream PI3K/Akt inhibition, suggesting that PART1 has a key role in restraining the aggressive ability of GC cells and providing a novel perspective on lncRNAs in GC progression.
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24
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Yang S, Ye Z, Wang Z, Wang L. High mobility group box 2 modulates the progression of osteosarcoma and is related with poor prognosis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1082. [PMID: 33145301 PMCID: PMC7576003 DOI: 10.21037/atm-20-4801] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background Increased expression of high mobility group box 2 (HMGB2) has been reported to promote the progression of several malignancies and be related to poor outcome. However, few studies have explored the relationship between HMGB2 and osteosarcoma. In this study, we aimed to obtain a better understanding of HMGB2 and its function in osteosarcoma. Methods Utilizing osteosarcoma paraffin sections and osteosarcoma cell lines, we observed the clinico-pathological relationship of osteosarcoma with HMGB2 expression and investigated the functions of HMGB2 in vitro. The possible pathways and regulation networks in which HMGB2 is involved were further explored through analysis of miRNA, mRNA and lncRNA micro array data sets. Results Strong expression of HMGB2 was found to be related with Enneking staging (P=0.002), tumor size (P=0.006), metastasis (P<0.001), and survival (P=0.011) in osteosarcoma. Multivariate analysis revealed that HMGB2 might have independent prognostic value in osteosarcoma (P=0.022). Kaplan-Meier curves and the log-rank test showed that survival time was significantly reduced in OS patients with strong HMGB2 expression (P=0.0056). In vitro experiments showed that HMGB2 overexpression promoted cell proliferation and enhanced the migration and invasion ability of osteosarcoma cells. Gene Ontology (GO) term analysis of osteosarcoma cell lines revealed HMGB2 to have various functions and to be mainly enriched in regulation of cell proliferation, cell death, and DNA binding. A competing endogenous RNA (ceRNA) network of miR-139-5p and six candidate lncRNAs was also suggested as targeting HMGB2 in osteosarcoma. Conclusions Our findings suggest that HMGB2 might have various functions in promoting the progression of osteosarcoma and may serve as a new target for osteosarcoma research.
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Affiliation(s)
- Shicong Yang
- Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ziyin Ye
- Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhuo Wang
- Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liantang Wang
- Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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25
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Cámara-Quílez M, Barreiro-Alonso A, Rodríguez-Bemonte E, Quindós-Varela M, Cerdán ME, Lamas-Maceiras M. Differential Characteristics of HMGB2 Versus HMGB1 and their Perspectives in Ovary and Prostate Cancer. Curr Med Chem 2020; 27:3271-3289. [PMID: 30674244 DOI: 10.2174/0929867326666190123120338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 10/28/2018] [Accepted: 12/06/2018] [Indexed: 01/24/2023]
Abstract
We have summarized common and differential functions of HMGB1 and HMGB2 proteins with reference to pathological processes, with a special focus on cancer. Currently, several "omic" approaches help us compare the relative expression of these 2 proteins in healthy and cancerous human specimens, as well as in a wide range of cancer-derived cell lines, or in fetal versus adult cells. Molecules that interfere with HMGB1 functions, though through different mechanisms, have been extensively tested as therapeutic agents in animal models in recent years, and their effects are summarized. The review concludes with a discussion on the perspectives of HMGB molecules as targets in prostate and ovarian cancers.
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Affiliation(s)
- María Cámara-Quílez
- EXPRELA Group, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxia. Facultade de Ciencias, INIBIC- Universidade da Coruna, Campus de A Zapateira, 15071, A Coruna, Spain
| | - Aida Barreiro-Alonso
- EXPRELA Group, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxia. Facultade de Ciencias, INIBIC- Universidade da Coruna, Campus de A Zapateira, 15071, A Coruna, Spain
| | - Esther Rodríguez-Bemonte
- EXPRELA Group, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxia. Facultade de Ciencias, INIBIC- Universidade da Coruna, Campus de A Zapateira, 15071, A Coruna, Spain
| | - María Quindós-Varela
- Translational Cancer Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Carretera del Pasaje s/n, 15006 A Coruña, Spain
| | - M Esperanza Cerdán
- EXPRELA Group, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxia. Facultade de Ciencias, INIBIC- Universidade da Coruna, Campus de A Zapateira, 15071, A Coruna, Spain
| | - Mónica Lamas-Maceiras
- EXPRELA Group, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxia. Facultade de Ciencias, INIBIC- Universidade da Coruna, Campus de A Zapateira, 15071, A Coruna, Spain
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26
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Hong JH, Jin EH, Chang IA, Kang H, Lee SI, Sung JK. Association Between lncRNA HULC rs7763881 Polymorphism and Gastric Cancer Risk. PHARMACOGENOMICS & PERSONALIZED MEDICINE 2020; 13:121-126. [PMID: 32308466 PMCID: PMC7154033 DOI: 10.2147/pgpm.s247082] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
Purpose Gastric cancer (GC) is one of the most common cancers in the world. Recently, several studies have suggested that single-nucleotide polymorphisms (SNPs) of long noncoding RNA (lncRNA) are associated with GC risk. However, the association of the lncRNA highly upregulated in liver cancer (HULC) SNP with GC risk is not yet known. The aims of this study were to evaluate the association between HULC rs7763881 SNP and the risk of GC and GC subgroups via a case–control study. Patients and Methods rs7763881 was genotyped using TaqMan genotyping assay with 459 GC patients and 379 controls. Results A significant association between HULC rs7763881 SNP and GC risk was not found. However, after adjustment for age and gender, the rs7763881 recessive model (CC) showed a significant association with an increased GC risk in the undifferentiated (odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.17–2.94, P = 0.009), diffuse-type GC (OR = 1.72, 95% CI = 1.05–2.82, P = 0.033), LNM-positive (OR = 2.02, 95% CI = 1.24–3.27, P = 0.004), T3/T4 (OR = 1.75, 95% CI = 1.05–2.91, P = 0.032), and tumor stage III (OR = 2.01, 95% CI = 1.17–3.45, P = 0.011) subgroups when compared to the rs7763881 combined genotypes (AA+AC). Furthermore, after adjusting for age and gender, the rs7763881 additive model (CC) indicated a significantly higher GC risk than rs7763881 AA genotype in the undifferentiated (OR = 1.96, 95% CI = 1.15–3.32, P = 0.013), diffuse-type GC (OR = 2.08, 95% CI = 1.23–3.52, P = 0.004), and LNM-positive (OR = 2.00, 95% CI = 1.14–3.49, P = 0.016) subgroups. Conclusion Our findings suggest that the HULC rs7763881 SNP is associated with increased susceptibility to GC. However, further studies are required to validate our results in large populations as well as different ethnic groups.
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Affiliation(s)
- Jang Hee Hong
- Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic of Korea.,Department of Pharmacology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Eun-Heui Jin
- Research Institute for Medical Sciences, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - In Ae Chang
- Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Hyojin Kang
- Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Sang-Il Lee
- Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Jae Kyu Sung
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Republic of Korea
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27
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Wang C, Zhuang X, Xu J, Dai Z, Wu W, Zhang C, Lin S, Chen S, Lin H, Tang W. Variants of MIR137HG Genes are Associated with Liver Cancer Risk in Chinese Li Population. Onco Targets Ther 2020; 13:1809-1818. [PMID: 32184616 PMCID: PMC7053808 DOI: 10.2147/ott.s225669] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 02/11/2020] [Indexed: 12/20/2022] Open
Abstract
Background Liver cancer (LC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide, and its incidence rate is high in China. Methods In this study, we aimed to investigate the contribution of MIR137HG (MIR137 Host Gene) polymorphisms to LC risk in a case–control study with 432 LC patients and 430 healthy controls. A logistic recession model was used to evaluate the effects of candidate single nucleotide polymorphisms (SNPs) on LC risk. HaploReg v 4.1 database was conducted to predict the potential functionality of SNPs. Results The results revealed that rs17371457 and rs7554283 in the MIR137HG gene were correlated with an enhanced LC risk under the allele (P = 0.001 and P = 0.043, respectively) and genetic models (P < 0.05). When the sample was stratified by gender and age, statistically significant associations were found. Rs9440302, rs17371457 and rs7554283 were associated with an increased the risk of LC among individuals aged >55 years (P < 0.05); rs17371457 was related to higher LC risk in males (P < 0.05). Similarly, the haplotype AG constituted by rs12333983 and rs3735451 significantly increased LC risk in Chinese Li population (P = 0.043). Six SNPs distributed in MIR137HG were successfully predicted as regulatory SNPs with different biological functions. Conclusion Our research firstly showed that MIR137HG gene polymorphisms were implicated in LC susceptibility among Chinese Li population.
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Affiliation(s)
- Chaoying Wang
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People's Republic of China
| | - Xiaohong Zhuang
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People's Republic of China
| | - Junnv Xu
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People's Republic of China.,Hainan Medical University, Haikou, Hainan 571199, People's Republic of China
| | - Zhisheng Dai
- Department of Medical Oncology, The Second People's Hospital of Hainan Province, Wuzhishan, Hainan 572200, People's Republic of China
| | - Weixiong Wu
- Intensive Care Medicine 1 District, The Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan 570311, People's Republic of China
| | - Chengsheng Zhang
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People's Republic of China
| | - Shu Lin
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People's Republic of China
| | - Sehong Chen
- Department of Medical Oncology, The Second People's Hospital of Hainan Province, Wuzhishan, Hainan 572200, People's Republic of China
| | - Haifeng Lin
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People's Republic of China
| | - Wenjun Tang
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People's Republic of China
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Hu J, Ji C, Hua K, Wang X, Deng X, Li J, Graham D, Fang L. Hsa_circ_0091074 regulates TAZ expression via microRNA‑1297 in triple negative breast cancer cells. Int J Oncol 2020; 56:1314-1326. [PMID: 32319577 DOI: 10.3892/ijo.2020.5000] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 01/31/2020] [Indexed: 12/24/2022] Open
Abstract
Triple negative breast cancer (TNBC) has the highest recurrence, metastasis and mortality rate of all breast cancer subtypes, due to its typically more aggressive characteristics and lack of effective targeted treatment options. The Hippo pathway is a signaling cascade composed of a group of conserved kinases, which serves an important role in almost all cancer types. Both circular RNAs (circRNAs) and microRNAs (miRNAs) are types of non‑coding RNAs, which influence cancer progression. CircRNAs have been demonstrated to serve as miRNA 'sponges', binding to miRNAs to inhibit their function. In the present study, it was revealed that circular RNA hsa_circ_0091074 binds miR‑1297, and that there is an inverse association between the expression levels of the two non‑coding RNAs in breast cells, indicating that hsa_circ_0091074 may serve as an endogenous 'sponge' for miR‑1297. Subsequently, the potential function and mechanism underlying the involvement of miR‑1297 in breast cancer was investigated via MTT, colony formation, wound healing and cell cycle assays. Increased miR‑1297 expression resulted in a decrease in the protein levels of critical Hippo pathway transcriptional mediator Transcriptional coactivator with PDZ‑binding motif (TAZ), which is a putative target of miR‑1297. This was confirmed using dual‑luciferase reporter assays, which revealed that miR‑1297 targets TAZ by binding its 3'‑untranslated region (3'UTR). The current results indicate that miR‑1297 serves as a suppressor of breast cancer cell proliferation and invasiveness, and that this can be partially reversed by hsa_circ_0091074, suggesting that the hsa_circ_0091074/miR‑1297/TAZ/TEAD4 axis may represent a potential therapeutic target for triple negative breast cancer in the future.
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Affiliation(s)
- Jiashu Hu
- Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Changle Ji
- Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Kaiyao Hua
- Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Xuehui Wang
- Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Xiaochong Deng
- Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Jiayi Li
- Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
| | - Dinny Graham
- Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales 2145, Australia
| | - Lin Fang
- Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
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Zhang Z, Li M, Zhang Z. lncRNA MALAT1 modulates oxaliplatin resistance of gastric cancer via sponging miR-22-3p. Onco Targets Ther 2020; 13:1343-1354. [PMID: 32104001 PMCID: PMC7026158 DOI: 10.2147/ott.s196619] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 01/30/2019] [Indexed: 02/06/2023] Open
Abstract
Objective Various regulatory mechanisms have been demonstrated to be associated with cancer progression. ncRNA and mRNA play important roles in gastric cancer (GC) cell growth and drug resistance, respectively. However, the regulatory network of ncRNA and mRNA in GC oxaliplatin (OXA) resistance has not been fully clarified. Methods The expression of miR-22-3p, MALAT1, and zinc finger protein 91 (ZFP91) was detected in tissues and cells using quantitative real-time PCR. The protein level of ZFP91 was measured by Western blot analysis. Luciferase reporter, pull-down, and RNA immunoprecipitation assays were used to determine the relationship between MALAT1, miR-22-3p, and ZFP91. MTT assay was applied to measure cell survival and proliferation. Cell apoptosis was detected using flow cytometry. Tumor xenograft assay was used to detect the function of miR-22-3p in vivo. Results In this study, we found that MALAT1 and ZFP91 expression was upregulated while the expression of miR-22-3p was downregulated in GC/OXA tissues and cells. Additionally, miR-22-3p was a target miRNA of MALAT1 and ZFP91 was a target mRNA of miR-22-3p. Functional studies showed that the knockdown of MALAT1 or overexpression of miR-22-3p inhibited GC/OXA cell survival, proliferation, and drug resistance as well as induced apoptosis, which could be reversed by the inhibition of miR-22-3p or overexpression of ZFP91. Conclusion We observed a new regulatory network for MALAT1 in drug resistance of GC. MALAT1 modulates ZFP91 to promote GC cells OXA resistance via sponging miR-22-3p.
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Affiliation(s)
- Zhenming Zhang
- Department II of General Surgery, Zhangye People's Hospital Affiliated to Hexi University, Zhangye, Gansu, China
| | - Ming Li
- Department II of General Surgery, Zhangye People's Hospital Affiliated to Hexi University, Zhangye, Gansu, China
| | - Zhitao Zhang
- Department of Oncology, Zhangye People's Hospital Affiliated to Hexi University, Zhangye, Gansu, China
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30
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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, Hebei 050017, People's Republic of China.,Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, People's Republic of China.,Department of General SurgeryⅡ, Baoding First Central Hospital, Baoding, Hebei 071000, People's Republic of China
| | - Jiangqiao Zhao
- Department of General Surgery, Cangzhou People's Hospital, Cangzhou, Hebei 061000, 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, Hebei 050017, People's Republic of China.,Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, People's Republic of China
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31
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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: 58] [Impact Index Per Article: 9.7] [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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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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Li HT, Pei XR, Li HT, Hao ML. Long-chain non-coding RNA SNHG14 regulates proliferation and apoptosis of gastric cancer cells by targeting miR-144-3p. Shijie Huaren Xiaohua Zazhi 2019; 27:1304-1312. [DOI: 10.11569/wcjd.v27.i21.1304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Long-chain non-coding RNAs (lncRNAs) are closely related to the development of gastric cancer. LncRNA SNHG14 play an oncogene role in tumorigenesis, but its mechanism of action in gastric cancer has not been elucidated. Bioinformatics prediction showed that miR-144-3p may be a target gene of SNHG14, but whether SNHG14 participates in the development of gastric cancer by regulating the expression of microRNA-144-3p (miR-144-3p) is unknown.
AIM To investigate whether the lncRNA SNHG14 can regulate the proliferation and apoptosis of gastric cancer cells by targeting miR-144-3p.
METHODS Real-time quantitative polymerase chain reaction was used to detect the expression of SNHG14 and miR-144-3p in normal human gastric epithelial cells and gastric cancer cells. Human gastric cancer MGC-803 cells were cultured in vitro and randomly divided into five groups: NC group, si-con group, si-SNHG14 group, si-SNHG14 + anti-miR-con group, and si-SNHG14 + anti-miR-144-3p group. MTT assay was used to detect the proliferation of cells in each group. Flow cytometry was used to detect the apoptosis of cells. The dual luciferase reporter system was used to validate whether there is a targeted regulatory relationship between SNHG14 and miR-144-3p. The expression of CyclinD1, Bcl-2, p21, Bcl-2-associated X protein (Bax), and PI3K/AKT signaling pathway-related proteins was detected by Western blot.
RESULTS The expression level of SNHG14 in gastric cancer cells was significantly higher than that in normal gastric epithelial cells (P < 0.05), while the expression level of miR-144-3p was significantly decreased (P < 0.05). Compared with the NC group and si-con group, the proliferation of MGC-803 cells in the si-SNHG14 group was significantly decreased (P < 0.05), and the apoptosis rate was significantly increased (P < 0.05). The expression of p-AKT, CyclinD1, Bcl-2, and p-PI3K protein was significantly decreased (P < 0.05), while the expression of p21, Bax, and cleaved caspase-3 protein was significantly increased (P < 0.05). The dual luciferase reporter assay showed that SNHG14 can bind to miR-144-3p and negatively regulate the expression and activity of miR-144-3p. Interference with miR-144-3p partially reversed the effect of silencing SNHG14 on the proliferation, apoptosis, and PI3K/AKT signaling pathways in gastric cancer cells.
CONCLUSION SNHG14 can promote the proliferation of gastric cancer cells and inhibit apoptosis by targeting and down-regulating the expression of miR-144-3p, which may play a role by activating the PI3K/AKT signaling pathway.
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Affiliation(s)
- Hao-Tian Li
- General Surgery Department of Tianjin Taida Hospital Tianjin 300457, China
| | - Xiao-Rui Pei
- General Surgery Department of Tianjin Taida Hospital Tianjin 300457, China
| | - Hong-Tao Li
- General Surgery Department of Tianjin Taida Hospital Tianjin 300457, China
| | - Ming-Li Hao
- General Surgery Department of Tianjin Taida Hospital Tianjin 300457, China
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Hou ZH, Xu XW, Fu XY, Zhou LD, Liu SP, Tan DM. Long non-coding RNA MALAT1 promotes angiogenesis and immunosuppressive properties of HCC cells by sponging miR-140. Am J Physiol Cell Physiol 2019; 318:C649-C663. [PMID: 31693399 DOI: 10.1152/ajpcell.00510.2018] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in adults. Previous studies in our laboratory found that long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated in HCC cells, which could affect the metastasis and invasion of HCC. However, the underlying mechanism remains unknown. Herein, we studied the interaction between MALAT1 and miR-140 on the regulation of angiogenesis and immunosuppressive properties. We revealed that the expression of MALAT1 and VEGF-A was significantly increased in HCC cells. Knockdown of MALAT1 in HCC cells suppressed the production of VEGF-A, impaired the angiogenesis of HUVECs, and facilitated the polarization of macrophage toward the M1 subset. Mechanistically, the interaction between MALAT1 and miR-140 or between miR-140 and VEGF-A was confirmed by multiple assays. Besides, a negative correlation between MALAT1 and miR-140 was found in HCC tissues. Furthermore, miR-140 inhibition significantly increased VEGF-A expression, promoted angiogenesis of HUVECs, and redirected the polarization of macrophages toward the M2 subset. In addition, in vivo studies also verified the regulatory network of the MALAT1/miR-140 axis on VEGF-A in HCC progression. In summary, this study revealed the mechanism that MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in the future.
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Affiliation(s)
- Zhou-Hua Hou
- Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, People's Republic of China.,Key Laboratory of Viral Hepatitis of Hunan Province, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Xu-Wen Xu
- Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, People's Republic of China.,Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Xiao-Yu Fu
- Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Le-Du Zhou
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Shui-Ping Liu
- Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, People's Republic of China.,Department of Microbiology, Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - De-Ming Tan
- Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, People's Republic of China.,Key Laboratory of Viral Hepatitis of Hunan Province, Xiangya Hospital, Central South University, Changsha, People's Republic of China
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35
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Fattahi S, Kosari-Monfared M, Golpour M, Emami Z, Ghasemiyan M, Nouri M, Akhavan-Niaki H. LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine. J Cell Physiol 2019; 235:3189-3206. [PMID: 31595495 DOI: 10.1002/jcp.29260] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 09/03/2019] [Indexed: 02/06/2023]
Abstract
Gastric cancer is the third leading cause of cancer death with 5-year survival rate of about 30-35%. Since early detection is associated with decreased mortality, identification of novel biomarkers for early diagnosis and proper management of patients with the best response to therapy is urgently needed. Long noncoding RNAs (lncRNAs) due to their high specificity, easy accessibility in a noninvasive manner, as well as their aberrant expression under different pathological and physiological conditions, have received a great attention as potential diagnostic, prognostic, or predictive biomarkers. They may also serve as targets for treating gastric cancer. In this review, we highlighted the role of lncRNAs as tumor suppressors or oncogenes that make them potential biomarkers for the diagnosis and prognosis of gastric cancer. Relatively, lncRNAs such as H19, HOTAIR, UCA1, PVT1, tissue differentiation-inducing nonprotein coding, and LINC00152 could be potential diagnostic and prognostic markers in patients with gastric cancer. Also, the impact of lncRNAs such as ecCEBPA, MLK7-AS1, TUG1, HOXA11-AS, GAPLINC, LEIGC, multidrug resistance-related and upregulated lncRNA, PVT1 on gastric cancer epigenetic and drug resistance as well as their potential as therapeutic targets for personalized medicine was discussed.
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Affiliation(s)
- Sadegh Fattahi
- Department of Genetics, Student Research Committee, Babol University of Medical Sciences, Babol, Iran.,Department of Genetics, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.,Department of Biochemistry, North Research Center, Pasteur Institute, Amol, Iran
| | | | - Monireh Golpour
- Department of Immunology, Molecular and Cell Biology Research Center, Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zakieh Emami
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Ghasemiyan
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Nouri
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Haleh Akhavan-Niaki
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
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36
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Li H, He C, Wang X, Wang H, Nan G, Fang L. MicroRNA-183 affects the development of gastric cancer by regulating autophagy via MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR signals. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:3163-3171. [PMID: 31352788 DOI: 10.1080/21691401.2019.1642903] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Huiying Li
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Chengyan He
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Xuekui Wang
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Hai Wang
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Guangxian Nan
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Ling Fang
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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37
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Mo Y, Fang RH, Wu J, Si Y, Jia SQ, Li Q, Bai JZ, She XN, Wang JQ. MicroRNA-329 upregulation impairs the HMGB2/β-catenin pathway and regulates cell biological behaviors in melanoma. J Cell Physiol 2019; 234:23518-23527. [PMID: 31219186 DOI: 10.1002/jcp.28920] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 05/17/2019] [Accepted: 05/20/2019] [Indexed: 12/29/2022]
Abstract
Melanoma is responsible for the majority of deaths caused by skin cancer. Antitumor activity of microRNA-329 (miR-329) has been seen in several human cancers. In this study, we identify whether miR-329 serves as a candidate regulator in melanoma. Melanoma-related differentially expressed genes were screened with its potential molecular mechanism predicted. Melanoma tissues and pigmented nevus tissues were collected, where the levels of miR-329 and high-mobility group box 2 (HMGB2) were determined. To characterize the regulatory role of miR-329 on HMGB2 and the β-catenin pathway in melanoma cell activities, miR-329 mimics, miR-329 inhibitors, and siRNA-HMGB2 were transfected into melanoma cells. Cell viability, migration, invasion, cell cycle, and apoptosis were assessed. miR-329 was predicted to influence melanoma by targeting HMGB2 via the β-catenin pathway. High level of HMGB2 and low miR-329 expression were observed in melanoma tissues. HMGB2 was targeted and negatively regulated by miR-329. In melanoma cells transfected with miR-329 mimics or siRNA-HMGB2, cell proliferation, migration, and invasion were impeded, yet cell cycle arrest and apoptosis were promoted, corresponding to decreased levels of β-catenin, cyclin D1, and vimentin and increased levels of GSK3β and E-cadherin. Collectively, our results show that miR-329 can suppress the melanoma progression by downregulating HMGB2 via the β-catenin pathway.
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Affiliation(s)
- You Mo
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Rui-Hua Fang
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Jiang Wu
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Yuan Si
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Shu-Qing Jia
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Qun Li
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Jing-Zhu Bai
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Xi-Ning She
- Department of Dermatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Jian-Qin Wang
- Institute of Dermatology, Guangzhou Medical University, Guangzhou, P.R. China.,Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, P.R. China
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38
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Delshad E, Shamsabadi FT, Bahramian S, Mehravar F, Maghsoudi H, Shafiee M. In silico identification of novel lncRNAs with a potential role in diagnosis of gastric cancer. J Biomol Struct Dyn 2019; 38:1954-1962. [PMID: 31179892 DOI: 10.1080/07391102.2019.1624615] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastric cancer (GC) is the second leading cause of cancer-related deaths in the world. Due to the shortage of adequate symptoms in the early stages, it is diagnosed when the tumor has spread to distant organs. Early recognition of GC enhances the chance of successful treatment. Molecular mechanisms of GC are still poorly understood. LncRNAs are emerging as new players in cancer in both oncogene and tumor suppressor roles. High-throughput technologies such as RNA-Seq, have revealed thousands of lncRNAs which are dysregulated in GC. In this study, we retrieved lncRNAs obtained by High-throughput technologies from OncoLnc database. Consequently, retrieved lncRNAs were compared in literature-based databases including PubMed. As a result, two lists, including experimentally validated lncRNAs and predicted lncRNAs were provided. We found 43 predicted lncRNAs that had not been experimentally validated in GC, so far. Further Bioinformatics analyses were performed to obtain the expression profile of predicted lncRNAs in tumor and normal tissues. Also, the roles and targets of predicted lncRNAs in GC were identified by related databases. Finally, using the GEPIA database was reviewed the significant relationship of predicted lncRNAs with the survival of GC patients. By recognizing the lncRNAs involved in initiation and progression of GC, they may be considered as potential biomarkers in the GC early diagnosis or targeted treatment and lead to novel therapeutic strategies. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Encieh Delshad
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh T Shamsabadi
- Department of Medical Biotechnology, Faculty of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Shabbou Bahramian
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh Mehravar
- Health Management and Social Development Research Center, Golestan university of Medical Sciences, Gorgan, Iran
| | | | - Mohammad Shafiee
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
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39
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Li F, Li X, Qiao L, Liu W, Xu C, Wang X. MALAT1 regulates miR-34a expression in melanoma cells. Cell Death Dis 2019; 10:389. [PMID: 31101802 PMCID: PMC6525244 DOI: 10.1038/s41419-019-1620-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 04/16/2019] [Accepted: 04/29/2019] [Indexed: 12/16/2022]
Abstract
Melanoma is one of the most common skin malignancies. Both microRNAs and long non-coding RNAs (lncRNAs) have critical roles in the progression of cancers, including melanoma. However, the underlying molecular mechanism has not been fully characterized. We demonstrated that miR-34a is negatively correlated with MALAT1 in melanoma cells and tumor specimens. Interestingly, MALAT1, which contains functional sequence-specific miR-34a-binding sites, regulates miR-34a stability in melanoma cells and in vivo. Importantly, MALAT1 was significantly enriched in the Ago2 complex, but not when the MALAT1-binding site of miR-34a was mutated. Furthermore, MALAT1 could be shown to regulate c-Myc and Met expression by functioning as a miR-34a sponge. Our results reveal an unexpected mode of action for MALAT1 as an important regulator of miR-34a.
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Affiliation(s)
- Fei Li
- Department of Dermatology, Air Force Medical Center, PLA, Beijing, China.
| | - Xinji Li
- Department of Radiation Oncology, Air Force Medical Center, PLA, Beijing, China
| | - Li Qiao
- Department of Dermatology, Air Force Medical Center, PLA, Beijing, China
| | - Wen Liu
- Department of Dermatology, Air Force Medical Center, PLA, Beijing, China
| | - Chengshan Xu
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Xiaogang Wang
- Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Beihang University, Beijing, China.
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40
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Wu Q, Shi M, Meng W, Wang Y, Hui P, Ma J. Long noncoding RNA FOXD3‐AS1 promotes colon adenocarcinoma progression and functions as a competing endogenous RNA to regulate SIRT1 by sponging miR‐135a‐5p. J Cell Physiol 2019; 234:21889-21902. [PMID: 31058315 DOI: 10.1002/jcp.28752] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 04/12/2019] [Accepted: 04/15/2019] [Indexed: 12/30/2022]
Affiliation(s)
- Qiong Wu
- Department of Gastroenterology, Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Min Shi
- Department of Gastroenterology, Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Wenying Meng
- Department of Gastroenterology, Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Yugang Wang
- Department of Gastroenterology, Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Pingping Hui
- Department of Gastroenterology, Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Jiali Ma
- Department of Gastroenterology, Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
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41
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Wang X, Gao S, Xie F, Li W, Li M, Yan N, Gao T, Fang L. Retracted
: High expression of TCF12 contributes to gastric cancer development via being target regulated by miR‐183 and activating PI3K/AKT pathway. J Cell Biochem 2019; 120:13903-13911. [DOI: 10.1002/jcb.28664] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 01/23/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Xuekui Wang
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Shen Gao
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Feng Xie
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Wei Li
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Miyang Li
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Ning Yan
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Tiehe Gao
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
| | - Ling Fang
- Department of Breast and Thyroid Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin China
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42
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Yu MJ, Zhao N, Shen H, Wang H. Long Noncoding RNA MRPL39 Inhibits Gastric Cancer Proliferation and Progression by Directly Targeting miR-130. Genet Test Mol Biomarkers 2019; 22:656-663. [PMID: 30452299 DOI: 10.1089/gtmb.2018.0151] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most prevalent malignant tumors displaying both high incidence and mortality throughout much of the world. Recently, long noncoding RNAs (lncRNAs) have been implicated in the development and progression of GC. MATERIALS AND METHODS In the present study, we investigated the biological function and molecular mechanisms of lncRNA MRPL39 in GC. RESULTS We found that MRPL39 was significantly downregulated in GC tissues and cell lines and that its expression level was negatively associated with carcinoma size, tumor, lymph node, metastasis (TNM) stage, and lymphatic metastasis. Patients with low MRPL39 expression levels revealed a short overall and disease-free survival period. Over-expression of MRPL39 in the GC cell lines BGC823 and SGC-7901 inhibited cell growth, proliferation, migration, and invasion. MiR-130, a putative target gene of MRPL39, displayed an inverse association with the expression of MRPL39 in GC tissues and cell lines. Moreover, a luciferase assay demonstrated a direct binding between the miR-130 and MRPL39, and the reintroduction of miR-130 abrogated the anti-tumor effect of MRPL39 on GC cells. CONCLUSION Taken together, these findings indicate that MRPL39 serves as a tumor suppressor by directly targeting miR-130 in GC, which suggests that it might be a novel biomarker in the diagnosis and prognosis of GC.
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Affiliation(s)
- Ming Jun Yu
- Department of Surgery, Hangzhou Third Hospital , Hangzhou, China
| | - Na Zhao
- Department of Surgery, Hangzhou Third Hospital , Hangzhou, China
| | - Haibin Shen
- Department of Surgery, Hangzhou Third Hospital , Hangzhou, China
| | - Haiming Wang
- Department of Surgery, Hangzhou Third Hospital , Hangzhou, China
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43
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Oskooei VK, Ghafouri-Fard S. Are long non-coding RNAs involved in the interaction circuit between estrogen receptor and vitamin D receptor? Meta Gene 2019. [DOI: 10.1016/j.mgene.2018.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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44
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Li H, Wang Y. Long Noncoding RNA (lncRNA) MIR22HG Suppresses Gastric Cancer Progression through Attenuating NOTCH2 Signaling. Med Sci Monit 2019; 25:656-665. [PMID: 30670679 PMCID: PMC6352764 DOI: 10.12659/msm.912813] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Long noncoding RNAs (lncRNAs) are important regulators in human disease, including cancers. LncRNA MIR22HG has been shown to inhibit the progression of endometrial carcinoma, lung cancer, and hepatocellular carcinoma. Its role in gastric cancer is unclear. This study investigated MIR22HG effects on gastric cancer. MATERIAL AND METHODS Gastric cancer tissues (n=43) and adjacent normal tissues (n=21) were collected. Patients' 5-year overall survival rate was analyzed. Human normal gastric mucosal cell line (GES-1) and gastric cancer cell lines (MKN-45, AGS, SGC-7901) were cultured. AGS and MKN-45 cells were transfected by pcDNA3 empty vector, pcDNA3-MIR22HG overexpression vector, MIR22HG siRNA and its negative control, NOTCH2 siRNA and its negative control, respectively. Proliferation was explored by CCK-8 assay. Migration and invasion were explored by Transwell. qRT-PCR and western blot were used to investigate mRNA and proteins expression, respectively. RESULTS MIR22HG expression was decreased in gastric cancer tissues and cells (P<0.05). Low MIR22HG expression indicated lower 5-year overall survival rate (P<0.05). Upregulation of MIR22HG inhibited AGS and MKN-45 cell proliferation, migration and invasion (all P<0.05). Downregulation of MIR22HG elevated AGS and MKN-45 cell proliferation, migration, and invasion (all P<0.05). MIR22HG negatively regulated NOTCH2 signaling. Silencing MIR22HG elevated HEY1 and nucleus NOTCH2 expression. Silencing of NOTCH2 suppressed AGS and MKN-45 cells proliferation, migration and invasion (all P<0.05). CONCLUSIONS LncRNA MIR22HG suppressed gastric cancer progression through attenuating NOTCH2 signaling.
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Affiliation(s)
- Huihui Li
- Department of Digestive System, Beilun People's Hospital, Ningbo, Zhejiang, China (mainland)
| | - Yue Wang
- Department of Pharmacology and Toxicology, Wright State University, Fairborn, OH, USA
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45
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MiR-137 suppresses migration and invasion by targeting EZH2-STAT3 signaling in human hepatocellular carcinoma. Pathol Res Pract 2018; 214:1980-1986. [DOI: 10.1016/j.prp.2018.08.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 07/26/2018] [Accepted: 08/06/2018] [Indexed: 02/07/2023]
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46
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Cui G, Cai F, Ding Z, Gao L. HMGB2 promotes the malignancy of human gastric cancer and indicates poor survival outcome. Hum Pathol 2018; 84:133-141. [PMID: 30296520 DOI: 10.1016/j.humpath.2018.09.017] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 09/23/2018] [Accepted: 09/29/2018] [Indexed: 11/16/2022]
Abstract
HMGB2 is an important protein in carcinogenesis. However, little is known about the specific role of HMGB2 in gastric cancer. In the present study, HMGB2 expression was evaluated in 198 primary gastric cancer tissues and their adjacent nontumor controls. The correlation between HMGB2 expression and clinico-pathological features and survival was assessed. The effect of HMGB2 on cell proliferation, invasion, and glycolysis was examined in vitro. The expression of HMGB2 was significantly increased in human gastric cancer when compared with nontumor tissues (P < .001). High HMGB2 expression correlated with large tumor size (P = .001), advanced T stage (P = .007), and presence of lymph node metastasis (P = .004). Moreover, high HMGB2 expression was validated as an independent prognostic factor in both univariate and multivariate analyses (P < .05). Experimentally, silencing HMGB2 expression by stable transfected shRNA significantly decreased the proliferation, invasion, and glycolysis of gastric cancer cells. In conclusion, HMGB2 is a novel prognostic biomarker for survival in gastric cancer, and knockdown HMGB2 expression in gastric cancer cells attenuated proliferation and invasion, and impaired glycolysis in gastric cancer cells. Hence, HMGB2 may serve as a new biomarker and a potential therapeutic target in gastric cancer.
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Affiliation(s)
- Guangfei Cui
- Department of Gastrointestinal Surgery, The First People's Hospital of Shangqiu, Shangqiu 476100, Henan Province, China.
| | - Feng Cai
- Department of Gastrointestinal Surgery, The First People's Hospital of Shangqiu, Shangqiu 476100, Henan Province, China.
| | - Zhanwei Ding
- Department of Gastrointestinal Surgery, The First People's Hospital of Shangqiu, Shangqiu 476100, Henan Province, China.
| | - Ling Gao
- Department of Gastrointestinal Surgery, The First People's Hospital of Shangqiu, Shangqiu 476100, Henan Province, China.
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47
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Yu H, Rong L. Emerging role of long non-coding RNA in the development of gastric cancer. World J Gastrointest Oncol 2018; 10:260-270. [PMID: 30254721 PMCID: PMC6147769 DOI: 10.4251/wjgo.v10.i9.260] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 06/14/2018] [Accepted: 06/27/2018] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is a common, worldwide malignancy and has a poor prognosis due to late diagnosis. Long non-coding RNAs (lncRNAs) are a significant subtype of RNA molecules with a length longer than 200 nucleotides (nt) that rarely encode proteins. In recent decades, deregulation of lncRNAs has been shown to be involved in tumorigenesis and tumor progression in various human carcinomas, including gastric cancer. Accumulating evidence has shown that some lncRNAs may function as diagnostic biomarkers or therapeutic targets for gastric cancer. Thus, exploring the specific functions of lncRNAs will help both gain a better understanding of the pathogenesis and develop novel treatments for gastric cancer. In this review, we highlight the expression and functional roles of lncRNAs in gastric cancer, and analyze the potential applications of lncRNAs as diagnostic markers and therapeutic targets.
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Affiliation(s)
- Hang Yu
- Department of Endoscopic Center, Peking University First Hospital, Beijing 100034, China
| | - Long Rong
- Department of Endoscopic Center, Peking University First Hospital, Beijing 100034, China
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Downregulation of MiR-1297 predicts poor prognosis and enhances gastric cancer cell growth by targeting CREB1. Biomed Pharmacother 2018; 105:413-419. [DOI: 10.1016/j.biopha.2018.05.094] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 05/19/2018] [Accepted: 05/20/2018] [Indexed: 11/24/2022] Open
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Lei L, Chen J, Huang J, Lu J, Pei S, Ding S, Kang L, Xiao R, Zeng Q. Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1. J Cell Physiol 2018; 234:134-151. [PMID: 30132842 DOI: 10.1002/jcp.26759] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 04/26/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Li Lei
- Department of Dermatology, Xiangya Hospital Central South University Changsha Hunan China
- Department of Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital, Central South University Changsha Hunan China
| | - Jing Chen
- Department of Dermatology Third Xiangya Hospital, Central South University Changsha Hunan China
| | - Jinhua Huang
- Department of Dermatology Third Xiangya Hospital, Central South University Changsha Hunan China
| | - Jianyun Lu
- Department of Dermatology Third Xiangya Hospital, Central South University Changsha Hunan China
| | - Shiyao Pei
- Department of Dermatology Third Xiangya Hospital, Central South University Changsha Hunan China
| | - Shu Ding
- Department of Dermatology Third Xiangya Hospital, Central South University Changsha Hunan China
| | - Liyang Kang
- Department of Dermatology Third Xiangya Hospital, Central South University Changsha Hunan China
| | - Rong Xiao
- Department of Dermatology Second Xiangya Hospital, Central South University Changsha Hunan China
| | - Qinghai Zeng
- Department of Dermatology Third Xiangya Hospital, Central South University Changsha Hunan China
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Gao S, Zhao ZY, Wu R, Zhang Y, Zhang ZY. Prognostic value of long noncoding RNAs in gastric cancer: a meta-analysis. Onco Targets Ther 2018; 11:4877-4891. [PMID: 30147339 PMCID: PMC6098423 DOI: 10.2147/ott.s169823] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background In the last few years, accumulating evidence has indicated that numerous long noncoding RNAs (lncRNAs) are abnormally expressed in gastric cancer (GC) and are associated with the survival of GC patients. This study aimed to conduct a meta-analysis on 19 lncRNAs (AFAP1 antisense RNA 1 [AFAP1-AS1], CDKN2B antisense RNA 1 [ANRIL], cancer susceptibility 15 [CASC15], colon cancer associated transcript 2 [CCAT2], gastric adenocarcinoma associated, positive CD44 regulator, long intergenic noncoding RNA [GAPLINC], H19, imprinted maternally expressed transcript [H19], HOX transcript antisense RNA [HOTAIR], HOXA distal transcript antisense RNA [HOTTIP], long intergenic non-protein coding RNA 673 [LINC00673], metastasis-associated lung adenocarcinoma transcript 1 [MALAT1], maternally expressed 3 [MEG3], promoter of CDKN1A antisense DNA damage activated RNA [PANDAR], Pvt1 oncogene [PVT1], SOX2 overlapping transcript [Sox2ot], SPRY4 intronic transcript 1 [SPRY4-IT1], urothelial cancer associated 1 [UCA1], X inactive specific transcript [XIST], ZEB1 antisense RNA 1 [ZEB1-AS1] and ZNFX1 antisense RNA 1 [ZFAS1]) to systematically estimate their prognostic value in GC. Methods The qualified literature was systematically searched in PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews (up to March 16, 2018), and one meta-analysis relating to the relationship between lncRNA expression and overall survival (OS) of GC patients was performed. The only evaluation criterion of survival results was OS. Results A total of 6,095 GC patients and 19 lncRNAs from 51 articles were included in the present study. Among the listed 19 lncRNAs, 18 lncRNAs (other than SPRY4-IT1) showed a significantly prognostic value (P<0.05). Conclusion This meta-analysis suggested that the abnormally expressed lncRNAs (AFAP1-AS1, ANRIL, CASC15, CCAT2, GAPLINC, H19, HOTAIR, HOTTIP, LINC00673, MALAT1, MEG3, PANDAR, PVT1, Sox2ot, UCA1, XIST, ZEB1-AS1 and ZFAS1) were significantly associated with the survival of GC patients, among which AFAP1-AS1, CCAT2, LINC00673, PANDAR, PVT1, Sox2ot, ZEB1-AS1 and ZFAS1 were strong candidates in predicting the prognosis of GC patients.
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Affiliation(s)
- Song Gao
- The Second Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China,
| | - Zhi-Ying Zhao
- Division of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Rong Wu
- The Second Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China,
| | - Yue Zhang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China,
| | - Zhen-Yong Zhang
- The Second Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China,
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