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Koopaie M, Arian-Kia S, Manifar S, Fatahzadeh M, Kolahdooz S, Davoudi M. Expression of Salivary miRNAs, Clinical, and Demographic Features in the Early Detection of Gastric Cancer: A Statistical and Machine Learning Analysis. J Gastrointest Cancer 2024; 56:15. [PMID: 39520622 DOI: 10.1007/s12029-024-01136-1] [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] [Accepted: 10/27/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE Gastric cancer ranks as one of the top five deadliest cancers worldwide and is often diagnosed at late stages. Analysis of saliva may provide a non-invasive approach for detection of malignancies in organs associated with the oral cavity. This research aims to analyze salivary microRNA expression together with clinical and demographic features with the aim of diagnosing gastric cancer. MATERIALS The study included 19 patients with early-stage gastric cancer and 19 healthy controls. Saliva samples were collected and processed for RNA isolation. Salivary expression of miR-223-3p and miR-21-5p were measured using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were generated to evaluate the accuracy of diagnostic models. Machine learning algorithms, multiple logistic regression, and principal component analysis (PCA) were used to assess the predictive power of miRNAs in conjunction with clinical-demographic features. RESULTS Significant upregulation of miR-223-3p and downregulation of miR-21-5p in saliva were observed in patients with gastric cancer. The area under ROC curve (AUC) values for salivary miR-21-5p, salivary miR-223-3p, and their multiple logistic regression were determined to be 0.723, 0.791, and 0.850, respectively. The AUC for multiple logistic regression model was 0.919. The PCA model led to the highest diagnostic odds ratio (DOR) of 134.33 (sensitivity = 0.785, specificity = 1.00, AUC = 903). Application of machine learning methods, and in particular a random forest algorithm, showed high accuracy in diagnosing patients with gastric cancer (sensitivity = 1.00, specificity = 0.857, AUC = 0.93). CONCLUSION The application of validated salivary diagnostics in clinical practice could help facilitate earlier diagnosis of gastric cancer and improve medical outcome. Expression of miR-21 and miR-223-3p in saliva together with clinical and demographic features, appears promising in screening for GC.
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Affiliation(s)
- Maryam Koopaie
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, North Kargar St, P.O.BOX:14395-433, Po. Code, Tehran, 14399-55991, Iran.
| | - Sasan Arian-Kia
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, North Kargar St, P.O.BOX:14395-433, Po. Code, Tehran, 14399-55991, Iran
| | - Soheila Manifar
- Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahnaz Fatahzadeh
- Division of Oral Medicine, Department of Oral Medicine, Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ, 07103, USA
| | - Sajad Kolahdooz
- Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran
| | - Mansour Davoudi
- Department of Computer Science and Engineering and IT, School of Electrical and Computer Engineering, Shiraz University, Shiraz, Iran
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Guo J, Zhong L, Momeni MR. MicroRNA-155 and its exosomal form: Small pieces in the gastrointestinal cancers puzzle. Cell Biol Toxicol 2024; 40:77. [PMID: 39283408 PMCID: PMC11405467 DOI: 10.1007/s10565-024-09920-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 09/04/2024] [Indexed: 09/22/2024]
Abstract
Gastrointestinal (GI) cancers are common cancers that are responsible for a large portion of global cancer fatalities. Due to this, there is a pressing need for innovative strategies to identify and treat GI cancers. MicroRNAs (miRNAs) are short ncRNAs that can be considered either cancer-causing or tumor-inhibiting molecules. MicroRNA-155, also known as miR-155, is a vital regulator in various cancer types. This miRNA has a carcinogenic role in a variety of gastrointestinal cancers, including pancreatic, colon, and gastric cancers. Since the abnormal production of miR-155 has been detected in various malignancies and has a correlation with increased mortality, it is a promising target for future therapeutic approaches. Moreover, exosomal miR-155 associated with tumors have significant functions in communicating between cells and establishing the microenvironment for cancer in GI cancers. Various types of genetic material, such as specifically miR-155 as well as proteins found in cancer-related exosomes, have the ability to be transmitted to other cells and have a function in the advancement of tumor. Therefore, it is critical to conduct a review that outlines the diverse functions of miR-155 in gastrointestinal malignancies. As a result, we present a current overview of the role of miR-155 in gastrointestinal cancers. Our research highlighted the role of miR-155 in GI cancers and covered critical issues in GI cancer such as pharmacologic inhibitors of miRNA-155, miRNA-155-assosiated circular RNAs, immune-related cells contain miRNA-155. Importantly, we discussed miRNA-155 in GI cancer resistance to chemotherapy, diagnosis and clinical trials. Furthermore, the function of miR-155 enclosed in exosomes that are released by cancer cells or tumor-associated macrophages is also covered.
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Affiliation(s)
- Jinbao Guo
- Department of Thoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
| | - Li Zhong
- Department of Gynecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
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3
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Zhang Q, Du Z, Wang X, Li F, Liu Y, Sun J, Zhang L, Xiao Y, Lu X, Yu H, Liu T. Cell-free Nucleic Acid as Promising Diagnostic Biomarkers for Gastric Cancer: a Systematic Review. J Cancer 2024; 15:2900-2912. [PMID: 38706900 PMCID: PMC11064260 DOI: 10.7150/jca.92704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 03/09/2024] [Indexed: 05/07/2024] Open
Abstract
Background: Gastric cancer (GC) is a common malignancy with early detection being crucial for survival. Liquid biopsy analysis using cell-free nucleic acid is a preferred method for detection. Hence, we conducted a systematic review to assess the diagnostic efficacy of cell-free nucleic acid markers for GC. Methods: We searched PubMed and ISI Web of Science databases for articles that conformed to our inclusion and exclusion criteria from 2012 to 2022. The following information was abstracted: first author, year of publication, country/region, age, male proportion, tumor stage for cases, specimen type, measurement method, targeted markers and diagnostic related indicators (including sensitivity, specificity, AUC, P-value). Results: Fifty-eight studies examined cell-free RNAs (cfRNAs) with a total of 62 individual circulating markers and 7 panels in serum or plasma, while 21 studies evaluated cell-free DNAs (cfDNAs) with 29 individual circulating markers and 7 panels. For individual cfRNAs, the median (range) sensitivity and specificity were 80% (21% - 98%) and 80% (54% - 99%), respectively. The median (range) sensitivity and specificity for cfRNA panels were 86% (83% - 90%) and 75% (60% - 98%), respectively. In comparison, the median (range) sensitivity and specificity reported for individual cfDNAs were 50% (18% - 96%) and 93% (57% - 100%), respectively, while cfDNA panels had a median (range) sensitivity and specificity of 85% (41% - 92%) and 73.5% (38% - 90%), respectively. The meta results indicate that cfRNA markers exhibit high sensitivity (80%) and low specificity (80%) for detecting GC, while cfDNA markers have lower sensitivity (59%) but higher specificity (92%). Conclusions: This review has demonstrated that cell-free nucleic acids have the potential to serve as useful diagnostic markers for GC. Given that both cfRNA and cfDNA markers have shown promising diagnostic performance for GC, the combination of the two may potentially enhance diagnostic efficiency.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Haixin Yu
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Tao Liu
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Bi W, Li J, Xiong M, Pan B, Zhang Z, Nasifu L, He B, Wang P. The diagnostic and prognostic role of miR-27a in cancer. Pathol Res Pract 2023; 247:154544. [PMID: 37235911 DOI: 10.1016/j.prp.2023.154544] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/11/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023]
Abstract
MicroRNA-27a (miR-27a) has been reported to be abnormally expressed in patients with cancer, and it could play potential roles as a diagnostic and prognostic biomarker of cancers. However, the diagnostic and prognostic role remains unclear. Hence, this meta-analysis, based on published data, was conducted to assess the utility of miR-27a as a diagnostic and prognostic marker in various cancers. To identify eligible studies, databases: Web of Science, PubMed, and CNKI were searched, with 868 literatures obtained, 16 of which were included in the Meta-analysis. The pooled results of studies conducted with serum/plasma showed that miR-27a was a valuable diagnostic biomarker in cancers (area under curve (AUC)= 0.91, sensitivity (SEN)= 0.84, specificity (SPE)= 0.85), with the diagnostic value slightly reduced in tumor tissue samples (AUC=0.83, SEN=0.78, SPE: 0.74). Additionally, the pooled results revealed that high expression of miR-27a predicted poor prognosis of cancer in serum/plasma (hazard ratio (HR) = 0.63, PHeterogeneity = 0.278, I2= 21.50%) but not in tumor tissue (HR = 0.98, PHeterogeneity =0.577, I2= 0.0). In brief, our results suggested that miR-27a in serum/plasma or tumor tissue could act as a diagnostic biomarker, and that miR-27a in serum/plasma could predict cancer patients' survival.
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Affiliation(s)
- Wen Bi
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
| | - Jingjing Li
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
| | - Mengqiu Xiong
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China.
| | - Bei Pan
- Medical College, Southeast University, Nanjing 210006, China.
| | - Zhongqiu Zhang
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China.
| | - Lubanga Nasifu
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China; Department of Biology, Muni University, Arua, Uganda.
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210006, China.
| | - Ping Wang
- School of Preclinical Medicine, Wannan Medical College, Wuhu 241001, China.
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Bernardes JGB, Fernandes MR, Rodrigues JCG, Vinagre LWMS, Pastana LF, Dobbin EAF, Medeiros JAG, Dias Junior LB, Bernardes GM, Bernardes IMM, Santos NPCD, Demachki S, Burbano RMR. Association of Androgenic Regulation and MicroRNAs in Acinar Adenocarcinoma of Prostate. Genes (Basel) 2022; 13:genes13040622. [PMID: 35456428 PMCID: PMC9030213 DOI: 10.3390/genes13040622] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/11/2022] [Accepted: 03/12/2022] [Indexed: 12/13/2022] Open
Abstract
Background: Prostate cancer represents 3.8% of cancer deaths worldwide. For most prostate cancer cells to grow, androgens need to bind to a cellular protein called the androgen receptor (AR). This study aims to demonstrate the expression of five microRNAs (miRs) and its influence on the AR formation in patients from the northern region of Brazil. Material and Methods: Eighty-four tissue samples were investigated, including nodular prostatic hyperplasia (NPH) and acinar prostatic adenocarcinoma (CaP). Five miRs (27a-3p, 124, 130a, 488-3p, and 506) were quantified using the TaqMan® Real Time PCR method and AR was measured using Western blotting. Results: Levels of miRs 124, 130a, 488-3p, and 506 were higher in NPH samples. Conversely, in the CaP cases, higher levels of miR 27a-3p and AR were observed. Conclusion: In the future, these microRNAs may be tested as markers of CaP at the serum level. The relative expression of AR was 20% higher in patients with prostate cancer, which suggests its potential as a biomarker for prostate malignancy.
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Affiliation(s)
- Julio Guilherme Balieiro Bernardes
- Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém 66050-160, Brazil; (J.G.B.B.); (L.B.D.J.); (I.M.M.B.)
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Marianne Rodrigues Fernandes
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
- Hospital Ophir Loyola, Belém 66063-240, Brazil
- Correspondence:
| | - Juliana Carla Gomes Rodrigues
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Lui Wallacy Morikawa Souza Vinagre
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Lucas Favacho Pastana
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Elizabeth Ayres Fragoso Dobbin
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Jéssyca Amanda Gomes Medeiros
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Leonidas Braga Dias Junior
- Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém 66050-160, Brazil; (J.G.B.B.); (L.B.D.J.); (I.M.M.B.)
| | | | | | - Ney Pereira Carneiro Dos Santos
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Samia Demachki
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
| | - Rommel Mario Rodriguez Burbano
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil; (J.C.G.R.); (L.W.M.S.V.); (L.F.P.); (E.A.F.D.); (J.A.G.M.); (N.P.C.D.S.); (S.D.); (R.M.R.B.)
- Hospital Ophir Loyola, Belém 66063-240, Brazil
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Farouk S, Khairy A, Salem AM, Soliman AF, Bader El Din NG. Differential Expression of miR-21, miR-23a, and miR-27a, and Their Diagnostic Significance in Egyptian Colorectal Cancer Patients. Genet Test Mol Biomarkers 2020; 24:825-834. [PMID: 33290159 DOI: 10.1089/gtmb.2020.0184] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: Colorectal cancer (CRC) rates are affected by genetics, ethnicity, and environmental factors; it is considered one of the most aggressive human malignancies with high mortality and morbidity rates worldwide due, in part, to its asymptomatic nature during the early stages of disease. Objective: Owing to the impact of microRNA (miRNA) dysregulation on CRC development and progression, this study was conducted to explore the expression levels of mir-21, -23a, and -27a in the sera and tissues of Egyptian CRC patients and to evaluate their diagnostic efficacy based on circulating levels. Methods: In the test phase, the relative expression levels of the studied miRNAs were evaluated in the sera of 70 participants (35 CRC patients and 35 healthy controls) using quantitative real-time-polymerase chain reaction and to verify their diagnostic value. The exploratory phase was designed to validate the tumor-derived trait by comparing the miRNA levels in the cancerous and adjacent noncancerous tissues. Results: The relative expression levels of the studied miRNAs were significantly upregulated in both serum and tumor tissues of the patients compared to their corresponding controls. In addition, significant positive correlations were found between the relative expression levels of the studied miRNAs in serum samples and their levels in the matched CRC tissues. The serum expression levels of mir-21 and -23a were more predictive of CRC than mir-27a. Conclusion: Circulating mir-21, -23a, and -27a expression levels appear to be valuable diagnostic biomarkers for CRC, especially when combined.
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Affiliation(s)
- Sally Farouk
- Microbial Biotechnology Department, National Research Centre, Giza, Egypt
| | - Ahmed Khairy
- Endemic Medicine Department, Kasr Elainy Hospitals, Cairo University, Giza, Egypt
| | - Ahmed M Salem
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Ahmed F Soliman
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
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Guo X, Li M. LINC01089 is a tumor-suppressive lncRNA in gastric cancer and it regulates miR-27a-3p/TET1 axis. Cancer Cell Int 2020; 20:507. [PMID: 33088215 PMCID: PMC7568383 DOI: 10.1186/s12935-020-01561-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 09/17/2020] [Indexed: 12/21/2022] Open
Abstract
Background Gastric cancer (GC) is one of the most common malignancies around the world. Recently, the role of long non-coding RNA (lncRNA) in cancer biology has become a hot research topic. This work aimed to explore the biological function and underlying mechanism of LINC01089 in GC. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to investigate the expression of LINC01089 in GC tissues and cells. The relationship between the expression level of LINC01089 and the clinicopathological parameters of GC was assessed. Cell models of LINC01089 overexpression, LINC01089 knockdown, miR-27a-3p overexpression, and miR-27a-3p inhibition were established by transfection. CCK-8 assay, BrdU assay, and Transwell assay were utilized to investigate the malignant biological behaviors of GC cell lines after transfection. Dual luciferase activity reporter assay, Pearson’s correlation analysis, and Western blot were utilized to the regulatory relationships among LINC01089, miR-27a-3p and tet methylcytosine dioxygenase 1 (TET1). Result LINC01089 down-regulation was observed in GC tissues and cell lines. Low expression level of LINC01089 in GC tissues was markedly linked to larger tumor size, higher T stage, as well as lymphatic metastasis of the patients. Functional experiments implied that LINC01089 overexpression impeded the proliferation, migration, as well as invasion of GC cells, whereas LINC01089 knockdown promoted the above malignant phenotypes. Additionally, up-regulation of miR-27a-3p was also observed in GC tissues. Functional experiments also showed that, miR-27a-3p overexpression boosted the malignant biological behaviors of GC cells; on the contrast, these phenotypes were impeded by miR-27a-3p inhibition. Moreover, LINC01089 interacted with and repressed miR-27a-3p, and miR-27a-3p antagonized the impact of LINC01089 on GC cells. Additionally, TET1 was verified as a target gene of miR-27a-3p, and could be positively regulated by LINC01089. Conclusion LINC01089 impedes the proliferation, migration, and invasion of GC cells by adsorbing miR-27a-3p and up-regulating the expression of TET1.
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Affiliation(s)
- Xufeng Guo
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430000 Hubei China
| | - Ming Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Zhangzhidong Road, Wuchang District, Wuhan, 430000 Hubei China
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Liu JR, Cai GY, Ning YC, Wang JC, Lv Y, Guo YN, Fu B, Hong Q, Sun XF, Chen XM. Caloric restriction alleviates aging-related fibrosis of kidney through downregulation of miR-21 in extracellular vesicles. Aging (Albany NY) 2020; 12:18052-18072. [PMID: 32963130 PMCID: PMC7585074 DOI: 10.18632/aging.103591] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 04/27/2020] [Indexed: 01/24/2023]
Abstract
Glomerulosclerosis and renal interstitial fibrosis occur with the aging kidney. In this study, we examined the expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF-1α) in the kidney of 3-month-old rats fed ad libitum (YAL), 24-month-old rats fed ad libitum (OAL) and 24-month-old rats subjected to a 70% calorie-restricted diet for 8 months (OCR). We found long-term caloric restriction (CR) ameliorated aging and aging-related fibrosis. CR ameliorated the increment of miR-21 and HIF-1α, as well as the decrement of PPARα in old ad libitum group. Human proximal tubular cells (HPTCs) presented phenotypes of senescence and epithelial to mesenchymal transition (EMT) under high-glucose conditions, in which senescence occurred earlier than EMT. Senescent cells secreted extracellular vesicles (EVs) which contained miR-21 into the recipient cells. Inhibiting miR-21 of donor cells prevented the occurrence of EMT in recipient cells. In addition, miR-21 induced EMT through targeting PPARα protein and consequently enhancing HIF-1α expression, although other pathways cannot be ruled out. These findings demonstrated that miR-21-containing EVs derived from the senescent cells could facilitate EMT of HPTCs via PPARα-HIF-1α signaling pathway. Long-term caloric restriction and caloric restriction mimetics alleviated aging-related-fibrosis of kidney through downregulation of miR-21.
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Affiliation(s)
- Jin-rui Liu
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China,Renal Transplant Division, Department of Nephrology, Zhengzhou No. 7 People's Hospital, Zhengzhou 450017, Henan, China
| | - Guang-yan Cai
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Yi-chun Ning
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Jing-chao Wang
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Yang Lv
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Ya-nan Guo
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Bo Fu
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Quan Hong
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Xue-feng Sun
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang-mei Chen
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
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Li K, Zhu X, Chen X, Wang X. MicroRNA‑27a‑3p promotes epithelial‑mesenchymal transition by targeting NOVA alternative splicing regulator 1 in gastric cancer. Mol Med Rep 2020; 21:1615-1622. [PMID: 32016460 DOI: 10.3892/mmr.2020.10949] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 06/22/2019] [Indexed: 11/05/2022] Open
Abstract
NOVA alternative splicing regulator 1 (NOVA1) dysregulation has been detected in the gastric cancer microenvironment. Decreased NOVA1 expression has been linked to the progression and poor prognosis of gastric cancer; however, the role of NOVA1 in regulating epithelial‑mesenchymal transition (EMT) remains unclear in this disease. Experimental evidence has shown that miR‑27a‑3p is a potential oncogene in gastric cancer. In the present study, we observed that miR‑27a‑3p expression was increased in gastric cancer and was inversely associated with overall survival. Overexpression of miR‑27a‑3p promoted EMT in AGS gastric cancer cells. Additionally, overexpression of miR‑27a‑3p inhibited NOVA1 expression, while silencing of NOVA1 promoted EMT in AGS cells. A total of 108 gastric cancer samples were examined for NOVA1 expression by immunohistochemistry. Decreased NOVA1 expression was linked to lymph node metastasis, tumor‑node‑metastasis stage and shorter overall survival. Therefore, these results indicated that NOVA1 could be a potential tumor suppressive gene and that miR‑27a‑3p promotes EMT by targeting NOVA1 in gastric cancer.
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Affiliation(s)
- Kai Li
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Xiangrong Zhu
- Department of General Surgery, Cixi People's Hospital, Cixi, Zhejiang 315300, P.R. China
| | - Xihua Chen
- Department of General Surgery, Cixi People's Hospital, Cixi, Zhejiang 315300, P.R. China
| | - Xiongtie Wang
- Department of General Surgery, Cixi People's Hospital, Cixi, Zhejiang 315300, P.R. China
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Zhang J, Cao Z, Yang G, You L, Zhang T, Zhao Y. MicroRNA-27a (miR-27a) in Solid Tumors: A Review Based on Mechanisms and Clinical Observations. Front Oncol 2019; 9:893. [PMID: 31572683 PMCID: PMC6751266 DOI: 10.3389/fonc.2019.00893] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 08/27/2019] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs (miRNAs) are a family of highly conserved, non-coding single-stranded RNAs transcribed as ~70 nucleotide precursors to an 18–22 nucleotide product (1). miRNAs can silence their homologous target genes at the post-transcriptional level, and these genes have been revealed to play an important role in tumorigenesis, invasion and metastasis (2). MicroRNA-27a (miR-27a), transcripted by miR-27a gene, has proved to implicate with many kinds of solid tumors, showing potential as a useful biomarker or drug target for clinical application. However, even though miR-27a has been reported in many cancers, the mechanism and signal pathways of miR-27 in oncogenesis, invasion, and metastasis are still obscure. Moreover, recent studies show that miR-27a pays an important role in epithelial-mesenchymal-transition, regulating tumor immune response, and chemoresistance. In this review, we summarize the current literature, demonstrate the established link between miR-27a and tumorigenesis, and focus on recently identified mechanisms. The review also aims to demonstrate the potential of miR-27a as a diagnostic and/or prognostic biomarker in solid tumors and to discuss the possibilities of targeted therapy and drug design.
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Affiliation(s)
- Jingcheng Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhe Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gang Yang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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11
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Mapekula L, Ramorola BR, Goolam Hoosen T, Mowla S. The interplay between viruses & host microRNAs in cancer - An emerging role for HIV in oncogenesis. Crit Rev Oncol Hematol 2019; 137:108-114. [PMID: 31014506 DOI: 10.1016/j.critrevonc.2019.02.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 02/16/2019] [Accepted: 02/17/2019] [Indexed: 12/12/2022] Open
Abstract
Human cancers attributed to viral infections represent a growing proportion of the global cancer burden, with these types of cancers being the leading cause of morbidity and mortality in some regions. The concept that viruses play a causal role in human cancers is not new, but the mechanism thereof, while well described for some viruses, still remains elusive and complex for others, especially in the case of HIV-associated B-cell derived cancers. In the last decade, compelling evidence has demonstrated that cellular microRNAs are deregulated in cancers, with an increasing number of studies identifying microRNAs as potential biomarkers for human cancer diagnosis, prognosis and therapeutic targets or tools. Recent research demonstrates that viruses and viral components manipulate host microRNA expressions to their advantage, and the emerging picture suggests that the virus/microRNA pathway interaction is defined by a plethora of complex mechanisms. In this review, we highlight the current knowledge on virus/microRNA pathway interactions in the context of cancer and provide new insights on HIV as an oncogenic virus.
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Affiliation(s)
- L Mapekula
- Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
| | - B R Ramorola
- Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
| | - T Goolam Hoosen
- Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
| | - S Mowla
- Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa.
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12
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Wei H, Pu K, Liu XG, Li BX, Zhang HS, Wang H, Wang H, Sun WM, Wang YP. The diagnostic value of circulating microRNAs as a biomarker for gastric cancer: A meta‑analysis. Oncol Rep 2019; 41:87-102. [PMID: 30320349 PMCID: PMC6278421 DOI: 10.3892/or.2018.6782] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 10/08/2018] [Indexed: 12/25/2022] Open
Abstract
Recently, cancer research microRNA studies have drawn great attention. However, the results of these studies have been inconsistent and variable regarding the availability of circulating miRNAs in gastric cancer (GC) diagnosis. Thus, results should be interpreted cautiously. The purpose of the present study was to assess the diagnostic performance of circulating miRNAs in GC diagnosis. We conducted a systematic and comprehensive approach for the inclusion of studies. The sensitivity, specificity, and diagnostic odds ratio were pooled with random effects models, and a summary of receiver operator characteristic (SROC) curves were plotted. The potential heterogeneity was assessed with Q test and I2 statistics. Subgroup analyses and meta‑regressions further investigated the sources of heterogeneity. A total of 77 studies from 48 articles were eligible for the meta‑analysis. The results revealed a sensitivity of 0.76, a specificity of 0.81, and an AUC of 0.86 for gastric cancer diagnosis with circulating miRNAs. In addition, subgroup analyses indicated that multiple miRNAs assays, non‑microarray screening approaches, and serum‑based miRNA assays exhibited good diagnostic performance in contrast to a single miRNA assay, microarray expression profiling screening, and plasma‑based miRNA group analysis. The diagnostic ability of miRNAs in early stage I‑II groups and the high expression group were approximately similar to that in the stage I‑IV groups and the low expression group. For the circulating miRNAs, our meta‑analysis identified a combination of multiple miRNAs, non‑microarray chip screening, and serum‑based miRNA assays were associated with the most effective GC diagnostic performance. However, many unclear molecular mechanisms limited the accuracy of the diagnostic results, and should be interpreted with caution. Further large‑scale prospective studies are required for validating the diagnostic applicability of circulating miRNAs in gastric cancer patients.
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Affiliation(s)
- Hui Wei
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Ke Pu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Xiao-Guang Liu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Bo-Xuan Li
- School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Heng-Shuo Zhang
- The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Huan Wang
- The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Hao Wang
- The Second Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Wei-Ming Sun
- Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Yu-Ping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
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13
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Chen J, Shen Z, Deng H, Zhou W, Liao Q, Mu Y. Long non-coding RNA biomarker for human laryngeal squamous cell carcinoma prognosis. Gene 2018; 671:96-102. [DOI: 10.1016/j.gene.2018.05.046] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 05/13/2018] [Indexed: 12/30/2022]
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14
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Bernier A, Sagan SM. The Diverse Roles of microRNAs at the Host⁻Virus Interface. Viruses 2018; 10:v10080440. [PMID: 30126238 PMCID: PMC6116274 DOI: 10.3390/v10080440] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 08/16/2018] [Accepted: 08/17/2018] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. Through this activity, they are implicated in almost every cellular process investigated to date. Hence, it is not surprising that miRNAs play diverse roles in regulation of viral infections and antiviral responses. Diverse families of DNA and RNA viruses have been shown to take advantage of cellular miRNAs or produce virally encoded miRNAs that alter host or viral gene expression. MiRNA-mediated changes in gene expression have been demonstrated to modulate viral replication, antiviral immune responses, viral latency, and pathogenesis. Interestingly, viruses mediate both canonical and non-canonical interactions with miRNAs to downregulate specific targets or to promote viral genome stability, translation, and/or RNA accumulation. In this review, we focus on recent findings elucidating several key mechanisms employed by diverse virus families, with a focus on miRNAs at the host–virus interface during herpesvirus, polyomavirus, retroviruses, pestivirus, and hepacivirus infections.
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Affiliation(s)
- Annie Bernier
- Department of Microbiology & Immunology, McGill University, Montréal, QC H3G 1Y6, Canada.
| | - Selena M Sagan
- Department of Microbiology & Immunology, McGill University, Montréal, QC H3G 1Y6, Canada.
- Department of Biochemistry, McGill University, Montréal, QC H3G 1Y6, Canada.
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15
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Link A, Kupcinskas J. MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer: Current insights and future perspectives. World J Gastroenterol 2018; 24:3313-3329. [PMID: 30122873 PMCID: PMC6092583 DOI: 10.3748/wjg.v24.i30.3313] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 06/10/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
Non-invasive diagnostic biomarkers may contribute to an early identification of gastric cancer (GC) and improve the clinical management. Unfortunately, no sensitive and specific screening biomarkers are available yet and the currently available approaches are limited by the nature of the disease. GC is a heterogenic disease with various distinct genetic and epigenetic events that occur during the multifactorial cascade of carcinogenesis. MicroRNAs (miRNAs) are commonly deregulated in gastric mucosa during the Helicobacter pylori infection and in stepwise manner from chronic gastritis, through preneoplastic conditions such as atrophic gastritis and intestinal metaplasia, to early dysplasia and invasive cancer. Identification of miRNAs in blood in 2008 led to a great interest on miRNA-based diagnostic, prognostic biomarkers in GC. In this review, we provide the most recent systematic review on the existing studies related to miRNAs as diagnostic biomarkers for GC. Here, we systematically evaluate 75 studies related to differential expression of circulating miRNAs in GC patients and provide novel view on various heterogenic aspects of the existing data and summarize the methodological differences. Finally, we highlight several important aspects crucial to improve the future translational and clinical research in the field.
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Affiliation(s)
- Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg 39120, Germany
| | - Juozas Kupcinskas
- Institute for Digestive Research and Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas LT-44307, Lithuania
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16
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Pelloni M, Coltrinari G, Paoli D, Pallotti F, Lombardo F, Lenzi A, Gandini L. Differential expression of miRNAs in the seminal plasma and serum of testicular cancer patients. Endocrine 2017; 57:518-527. [PMID: 27796811 DOI: 10.1007/s12020-016-1150-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 10/17/2016] [Indexed: 02/07/2023]
Abstract
Various microRNAs from the miR-371-3 and miR-302a-d clusters have recently been proposed as markers for testicular germ cell tumours. Upregulation of these miRNAs has been found in both the tissue and serum of testicular cancer patients, but they have never been studied in human seminal plasma. The aim of this study was, therefore, to assess the differences in the expression of miR-371-3 and miR-302a-d between the seminal plasma and serum of testicular cancer patients, and to identify new potential testicular cancer markers in seminal plasma. We investigated the serum and seminal plasma of 28 pre-orchiectomy patients subsequently diagnosed with testicular cancer, the seminal plasma of another 20 patients 30 days post-orchiectomy and a control group consisting of 28 cancer-free subjects attending our centre for an andrological check-up. Serum microRNA expression was analysed using RT-qPCR. TaqMan Array Card 3.0 platform was used for microRNA profiling in the seminal plasma of cancer patients. Results for both miR-371-3 and the miR-302 cluster in the serum of testicular cancer patients were in line with literature reports, while miR-371and miR-372 expression in seminal plasma showed the opposite trend to serum. On array analysis, 37 miRNAs were differentially expressed in the seminal plasma of cancer patients, and the upregulated miR-142 and the downregulated miR-34b were validated using RT-qPCR. Our study investigated the expression of miRNAs in the seminal plasma of patients with testicular cancer for the first time. Unlike in serum, miR-371-3 cannot be considered as markers in seminal plasma, whereas miR-142 levels in seminal plasma may be a potential marker for testicular cancer.
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Affiliation(s)
- Marianna Pelloni
- Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome "La Sapienza", Viale del Policlinico 155, 00161, Roma, Italy
| | - Giulia Coltrinari
- Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome "La Sapienza", Viale del Policlinico 155, 00161, Roma, Italy
| | - Donatella Paoli
- Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome "La Sapienza", Viale del Policlinico 155, 00161, Roma, Italy.
| | - Francesco Pallotti
- Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome "La Sapienza", Viale del Policlinico 155, 00161, Roma, Italy
| | - Francesco Lombardo
- Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome "La Sapienza", Viale del Policlinico 155, 00161, Roma, Italy
| | - Andrea Lenzi
- Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome "La Sapienza", Viale del Policlinico 155, 00161, Roma, Italy
| | - Loredana Gandini
- Laboratory of Seminology-Sperm Bank, Department of Experimental Medicine, University of Rome "La Sapienza", Viale del Policlinico 155, 00161, Roma, Italy
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Zhang Y, Guan DH, Bi RX, Xie J, Yang CH, Jiang YH. Prognostic value of microRNAs in gastric cancer: a meta-analysis. Oncotarget 2017; 8:55489-55510. [PMID: 28903436 PMCID: PMC5589675 DOI: 10.18632/oncotarget.18590] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 05/08/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Previous articles have reported that expression levels of microRNAs (miRNAs) are associated with survival time of patients with gastric cancer (GC). A systematic review and meta-analysis was performed to study the outcome of it. DESIGN Meta-analysis. METHODS English studies estimating expression levels of miRNAs with any of survival curves in GC were identified up till March 19, 2017 through performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two authors independently. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS). RESULTS Sixty-nine relevant articles about 26 miRNAs with 6148 patients were ultimately included. GC patients with high expression of miR-20b (HR=2.38, 95%CI=1.16-4.87), 21 (HR=1.77, 95%CI=1.01-3.08), 106b (HR=1.84, 95%CI=1.15-2.94), 196a (HR=2.66, 95%CI=1.94-3.63), 196b (HR=1.67, 95%CI=1.38-2.02), 214 (HR=1.84, 95%CI=1.27-2.67) or low expression of miR-125a (HR=2.06, 95%CI=1.26-3.37), 137 (HR=3.21, 95%CI=1.68-6.13), 141 (HR=2.47, 95%CI=1.34-4.56), 145 (HR=1.62, 95%CI=1.07-2.46), 146a (HR=2.60, 95%CI=1.63-4.13), 206 (HR=2.85, 95%CI=1.73-4.70), 218 (HR=2.61, 95%CI=1.74-3.92), 451 (HR=1.73, 95%CI=1.19-2.52), 486-5p (HR=2.45, 95%CI=1.65-3.65), 506 (HR=2.07, 95%CI=1.33-3.23) have significantly poor OS (P<0.05). CONCLUSIONS In summary, miR-20b, 21, 106b, 125a, 137, 141, 145, 146a, 196a, 196b, 206, 214, 218, 451, 486-5p and 506 demonstrate significantly prognostic value. Among them, miR-20b, 125a, 137, 141, 146a, 196a, 206, 218, 486-5p and 506 are strong biomarkers of prognosis in GC.
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Affiliation(s)
- Yue Zhang
- 1 First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, People's Republic of China
| | - Dong-Hui Guan
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Rong-Xiu Bi
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Jin Xie
- 2 Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Chuan-Hua Yang
- 3 Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
| | - Yue-Hua Jiang
- 4 Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, People's Republic of China
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Li B, Zhang H. Plasma microRNA-320 is a potential diagnostic and prognostic bio-marker in gastric cancer. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017; 10:7356-7361. [PMID: 31966576 PMCID: PMC6965298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 01/10/2017] [Indexed: 06/10/2023]
Abstract
OBJECTIVE MicroRNA-320 (MiR-320) had been reported to be down-regulated in several cancers. However, its clinical significance in gastric cancer remained unknown. In this study, we aimed to detect the expression of miR-320 and its clinical significance in gastric cancer. METHODS The relative expression levels of miR-320 in plasma of gastric cancer patients and healthy controls were detected using quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to estimate the diagnostic value of miR-320 in gastric cancer. Moreover, its prognostic value was assessed via Kaplan-Meier and Cox regression analyses. RESULTS Compared with healthy individuals, the plasma miR-320 expression in patients with gastric cancer was significantly decreased (P<0.001). The low plasma miR-320 expression was closely associated with TNM stage and lymph node metastasis (P<0.05). Furthermore, plasma miR-320 could be used to distinguish gastric cancer patients from healthy controls with an area under the curve (AUC) of 0.861. The sensitivity and specificity were 82.4% and 75.9%, respectively. Kaplan-Meier analysis revealed that patients with high expression of miR-320 had an obviously longer overall survival than those with low miR-320 expression (log rank test, P=0.003). MiR-320 could be an independent prognostic factor for patients with gastric cancer via univariate and multivariate analyses. CONCLUSIONS Plasma miR-320 is down-regulated and correlated with the progression of gastric cancer. What's more, miR-320 may be a potential bio-marker for the diagnosis and prognosis of gastric cancer patients.
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Affiliation(s)
- Baohui Li
- Department of Medical Medicine, Cangzhou Central HospitalCangzhou, Hebei, China
| | - Hongjie Zhang
- Department of Medical Safety, Cangzhou Central HospitalCangzhou, Hebei, China
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19
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Zhang L, Huang Z, Zhang H, Zhu M, Zhu W, Zhou X, Liu P. Prognostic value of candidate microRNAs in gastric cancer: A validation study. Cancer Biomark 2017; 18:221-230. [PMID: 27983528 DOI: 10.3233/cbm-160091] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Studies have reported the prognostic value of dysregulated microRNAs (miRNAs) in gastric cancer (GC). However, the results demonstrated so far are inconsistent. OBJECTIVE To better understand the miRNAs with prognostic relevance. METHODS Evaluable miRNAs were selected based on our selection criteria and further analyzed in formalin-fixed paraffin-embedded (FFPE) tissue samples of 169 GC patients using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS A total of 19 miRNAs were selected as candidate miRNAs. Among those miRNAs identified, high expression of miR-21-5p was related to poor overall survival (OS) and disease free survival (DFS) and was identified as an independent prognostic factor. Cases with high level of miR-200c-3p showed poor DFS. Subgroup analysis revealed that high expression of miR-21-5p and miR-222-3p was associated with poor OS and DFS in GC patients not received adjuvant chemotherapy. In male patients, high expression level of miR-21-5p was related to poor OS and DFS. CONCLUSIONS The present study confirmed that elevated level of miR-21-5p could serve as an independent predictor for poor OS and DFS of GC patients. Moreover, miR-200c-3p, miR-222-3p might also play important roles in the prognosis of GC patients. Further studies are warranted to validate our findings and identify the functions and mechanisms of these miRNAs.
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Wu F, Li J, Guo N, Wang XH, Liao YQ. MiRNA-27a promotes the proliferation and invasion of human gastric cancer MGC803 cells by targeting SFRP1 via Wnt/β-catenin signaling pathway. Am J Cancer Res 2017; 7:405-416. [PMID: 28401000 PMCID: PMC5385632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 10/18/2016] [Indexed: 06/07/2023] Open
Abstract
This study aims to elucidate the effects of microRNA-27a (miR-27a) on the proliferation and invasion of gastric cancer (GC) cells by targeting SFRP1 via Wnt/β-catenin signaling pathway. GC and normal adjacent tissues were collected from 273 GC patients. Human gastric cancer cell line (MGC803) and normal human gastric mucosal cell line (GES-1) were cultured. The miR-27a mRNA expression was analyzed using Quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) test was used to detect miR-27a and SFRP1 protein expressions. After transfection, cells were divided into five groups: the negative control (NC) group, the miR-27a inhibitor group, the miR-27a mimics group, the miR-27a inhibitor + SFRP1 siRNA group and the miR-27a mimics + SFRP1 overexpression group. Western blotting was conducted to test SFRP1 and Wnt/β-catenin protein expression. Analysis for the target gene of miR-27a was performed using Luciferase assay. Cell proliferation, migration and invasion were determined by CCK8 and Transwell assay. The dual-luciferase reporter assay system was applied to analyze the effects of miR-27a on Wnt/β-catenin signaling pathway. In GC tissue and cell line, miR-27a protein and mRNA expressions were up-regulated, and SFRP1 protein and mRNA expressions were down-regulated. Luciferase assay indicated that miR-27a might target SFRP1 and regulate its expressions. When miR-27a was down-regulated, SFRP1 was up-regulated, and β-catenin, Wnt, p-β-catenin, and p-Wnt were significantly down-regulated. Compared with the NC group, the proliferation, migration and invasion of GC cells were remarkably increased in the miR-27a group, but these were declined in the miR-27a mimics + SFRP1 overexpression group. The proliferation, migration and invasion of GC cells were elevated in the miR-27a inhibitor + SFRP1 siRNA group compared with the miR-27a inhibitor group. These results showed that miR-27a was highly expressed in GC tissues and cells, and it might promote cell proliferation, migration and invasion by targeting SFRP1 via the activation of Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Fang Wu
- Department of Oncology, The First Affiliated Hospital of Nanchang UniversityNanchang 330006, P. R. China
| | - Jun Li
- Department of Radiation Oncology, Jiangxi Cancer HospitalNanchang 330029, P. R. China
| | - Ni Guo
- Department of Oncology, The First Affiliated Hospital of Nanchang UniversityNanchang 330006, P. R. China
| | - Xiao-Hui Wang
- Department of Oncology, The First Affiliated Hospital of Nanchang UniversityNanchang 330006, P. R. China
| | - Yu-Qian Liao
- Department of Medical Oncology, Jiangxi Cancer HospitalNanchang 330029, P. R. China
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Cai Q, Wang T, Yang WJ, Fen X. Protective mechanisms of microRNA-27a against oxygen-glucose deprivation-induced injuries in hippocampal neurons. Neural Regen Res 2016; 11:1285-92. [PMID: 27651777 PMCID: PMC5020828 DOI: 10.4103/1673-5374.189194] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Hypoxic injuries during fetal distress have been shown to cause reduced expression of microRNA-27a (miR-27a), which regulates sensitivity of cortical neurons to apoptosis. We hypothesized that miR-27a overexpression attenuates hypoxia- and ischemia-induced neuronal apoptosis by regulating FOXO1, an important transcription factor for regulating the oxidative stress response. miR-27a mimic was transfected into hippocampal neurons to overexpress miR-27a. Results showed increased hippocampal neuronal viability and decreased caspase-3 expression. The luciferase reporter gene system demonstrated that miR-27a directly binded to FOXO1 3'UTR in hippocampal neurons and inhibited FOXO1 expression, suggesting that FOXO1 was the target gene for miR-27a. These findings confirm that miR-27a protects hippocampal neurons against oxygen-glucose deprivation-induced injuries. The mechanism might be mediated by modulation of FOXO1 and apoptosis-related gene caspase-3 expression.
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Affiliation(s)
- Qun Cai
- Department of Neonatology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Ting Wang
- Department of Emergency, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Wen-Jie Yang
- Medical College of Nantong University, Nantong, Jiangsu Province, China
| | - Xing Fen
- Department of Neonatology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, China
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Zhang M, Du X. Noncoding RNAs in gastric cancer: Research progress and prospects. World J Gastroenterol 2016; 22:6610-6618. [PMID: 27547004 PMCID: PMC4970485 DOI: 10.3748/wjg.v22.i29.6610] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/26/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Noncoding RNAs (ncRNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of ncRNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer (GC). In the past few years, an accumulating body of evidence has deepened our understanding of ncRNAs, and several emerging ncRNAs have been identified, such as PIWI-interacting RNAs (piRNAs) and circular RNAs (circRNAs). The competing endogenous RNA (ceRNA) networks include mRNAs, microRNAs, long ncRNAs (lncRNAs) and circRNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of ncRNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ceRNA network in GC.
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