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Wang X, Li Z, Zhang C. Integrated Analysis of Serum and Tissue microRNA Transcriptome for Biomarker Discovery in Gastric Cancer. ENVIRONMENTAL TOXICOLOGY 2025; 40:281-290. [PMID: 39400980 DOI: 10.1002/tox.24430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/25/2024] [Accepted: 08/31/2024] [Indexed: 10/15/2024]
Abstract
Gastric cancer (GC) poses a significant global health challenge, demanding a detailed exploration of its molecular landscape. Studies suggest that exposure to environmental pollutants can lead to changes in microRNA (miRNA) expression patterns, which may contribute to the development and progression of GC. MiRNAs have emerged as crucial regulators implicated in GC pathogenesis. The largest GC serum miRNA dataset to date, comprising 1417 non-cancer controls and 1417 GC samples was used. We conducted a comprehensive analysis of miRNA expression profiles. Differential expression analysis, co-expression network construction, and machine learning models were employed to identify key serum miRNAs and their association with clinical parameters. Weighted Gene Co-expression Network Analysis (WGCNA) and immune infiltration analysis were used to validate the importance of the key miRNA. A total of 1766 differentially expressed miRNAs were identified, with miR-1290, miR-1246, and miR-451a among the top up-regulated, and miR-6875-5p, miR-6784-5p, miR-1228-5p, and miR-6765-5p among the top down-regulated. WGCNA revealed that modules M1 and M5 were significantly associated with GC subtypes and disease status. MiRNA-target gene network analysis identified prognostically significant genes TP53, EMCN, CBX8, and ALDH1A3. Machine learning models LASSO, SVM, randomforest, and XGBOOST demonstrated the diagnostic potential of miRNA profiles. Tissue and serum miR-187 emerged as an independent prognostic factor, influencing patient survival across clinical parameters. Gene expression and immune cell infiltration were different in tissues stratified by miR-187 expression. In summary, the integration of differential gene expression, co-expression analysis, and immune cell profiling provided insights into the molecular intricacies of GC progression.
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Affiliation(s)
- Xinfeng Wang
- Department of Pharmacy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Zhuoran Li
- Department of Optometry, Fenyang College of Shanxi Medical University, Fenyang, China
| | - Chengyan Zhang
- Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
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Li M, Gao N, Wang SL, Guo YF, Liu Z. Hotspots and trends of risk factors in gastric cancer: A visualization and bibliometric analysis. World J Gastrointest Oncol 2024; 16:2200-2218. [PMID: 38764808 PMCID: PMC11099465 DOI: 10.4251/wjgo.v16.i5.2200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/08/2024] [Accepted: 03/11/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND The lack of specific symptoms of gastric cancer (GC) causes great challenges in its early diagnosis. Thus it is essential to identify the risk factors for early diagnosis and treatment of GC and to improve the survival rates. AIM To assist physicians in identifying changes in the output of publications and research hotspots related to risk factors for GC, constructing a list of key risk factors, and providing a reference for early identification of patients at high risk for GC. METHODS Research articles on risk factors for GC were searched in the Web of Science core collection, and relevant information was extracted after screening. The literature was analyzed using Microsoft Excel 2019, CiteSpace V, and VOSviewer 1.6.18. RESULTS A total of 2514 papers from 72 countries and 2507 research institutions were retrieved. China (n = 1061), National Cancer Center (n = 138), and Shoichiro Tsugane (n = 36) were the most productive country, institution, or author, respectively. The research hotspots in the study of risk factors for GC are summarized in four areas, namely: Helicobacter pylori (H. pylori) infection, single nucleotide polymorphism, bio-diagnostic markers, and GC risk prediction models. CONCLUSION In this study, we found that H. pylori infection is the most significant risk factor for GC; single-nucleotide polymorphism (SNP) is the most dominant genetic factor for GC; bio-diagnostic markers are the most promising diagnostic modality for GC. GC risk prediction models are the latest current research hotspot. We conclude that the most important risk factors for the development of GC are H. pylori infection, SNP, smoking, diet, and alcohol.
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Affiliation(s)
- Meng Li
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ning Gao
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Shao-Li Wang
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yu-Feng Guo
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zhen Liu
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Bakinowska E, Kiełbowski K, Skórka P, Dach A, Olejnik-Wojciechowska J, Szwedkowicz A, Pawlik A. Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer-A Narrative Review. Int J Mol Sci 2024; 25:5144. [PMID: 38791187 PMCID: PMC11121563 DOI: 10.3390/ijms25105144] [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: 04/08/2024] [Revised: 05/03/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
Non-coding RNAs (ncRNAs) represent a broad family of molecules that regulate gene expression, including microRNAs, long non-coding RNAs and circular RNAs, amongst others. Dysregulated expression of ncRNAs alters gene expression, which is implicated in the pathogenesis of several malignancies and inflammatory diseases. Gastric cancer is the fifth most frequently diagnosed cancer and the fourth most common cause of cancer-related death. Studies have found that altered expression of ncRNAs may contribute to tumourigenesis through regulating proliferation, apoptosis, drug resistance and metastasis. This review describes the potential use of ncRNAs as diagnostic and prognostic biomarkers. Moreover, we discuss the involvement of ncRNAs in the pathogenesis of gastric cancer, including their interactions with the members of major signalling pathways.
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Affiliation(s)
| | | | | | | | | | | | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (E.B.); (K.K.); (P.S.); (A.D.); (J.O.-W.); (A.S.)
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Huang Y, Shao Y, Yu X, Chen C, Guo J, Ye G. Global progress and future prospects of early gastric cancer screening. J Cancer 2024; 15:3045-3064. [PMID: 38706913 PMCID: PMC11064266 DOI: 10.7150/jca.95311] [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: 02/14/2024] [Accepted: 03/21/2024] [Indexed: 05/07/2024] Open
Abstract
Gastric cancer is a prevalent malignancy that poses a serious threat to global health. Despite advances in medical technologies, screening methods, and public awareness, gastric cancer remains a significant cause of morbidity and mortality worldwide. Early gastric cancer frequently does not present with characteristic symptoms, while advanced stage disease is characterized by a dismal prognosis. As such, early screening in gastric cancer is of great importance. In recent years, advances have been made globally in both clinical and basic research for the screening of early gastric cancer. The current predominant screening methods for early gastric cancer include imaging screening, endoscopic screening and serum biomarker screening. Imaging screening encompasses upper gastrointestinal barium meal, multidimensional spiral computed tomography (MDCT), Magnetic resonance imaging (MRI), and ultrasonography. Endoscopic screening methods include white light endoscopy, chromoendoscopy, computed virtual chromoendoscopy, and other endoscopic techniques like endocytoscopy, confocal laser endomicroscopy, optical coherence tomography and so on. Biomarkers screening involves the assessment of conventional biomarkers such as CEA, CA19-9 and CA72-4 as well as more emerging biomarkers such as peptides (PG, G-17, GCAA, TAAs and others), DNA (cfDNA, DNA methylation, MSI), noncoding RNA (miRNA, lncRNA, circRNA, and tsRNA) and others. Each screening method has its strengths and limitations. This article systematically summarizes worldwide progress and future development of early gastric cancer screening methods to provide new perspectives and approaches for early diagnostic and treatment advancements in gastric cancer worldwide.
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Affiliation(s)
- Yixiao Huang
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo 315020, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Yongfu Shao
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo 315020, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Xuan Yu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Chujia Chen
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Guoliang Ye
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo 315020, China
- Institute of Digestive Disease of Ningbo University, Ningbo 315020, China
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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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Matsuoka T, Yashiro M. Novel biomarkers for early detection of gastric cancer. World J Gastroenterol 2023; 29:2515-2533. [PMID: 37213407 PMCID: PMC10198055 DOI: 10.3748/wjg.v29.i17.2515] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/31/2023] [Accepted: 04/13/2023] [Indexed: 05/23/2023] Open
Abstract
Gastric cancer (GC) remains a leading cause of cancer-related death worldwide. Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms. GC is a heterogeneous disease associated with a number of genetic and somatic mutations. Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality. The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers: However, these approaches are invasive, costly, and time-consuming. Thus, novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current methods. Recent technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual disease. These biomarkers include circulating DNA, RNA, extracellular vesicles, and proteins, and their clinical applications are currently being investigated. The identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision medicine. This review provides an overview of current topics regarding the novel, recently developed diagnostic markers for GC.
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Affiliation(s)
- Tasuku Matsuoka
- Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka 5458585, Japan
| | - Masakazu Yashiro
- Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka 5458585, Japan
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MicroRNA-34c-5p exhibits anticancer properties in gastric cancer by targeting MAP2K1 to inhibit cell proliferation, migration, and invasion. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7375661. [PMID: 36203485 PMCID: PMC9532111 DOI: 10.1155/2022/7375661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 08/27/2022] [Indexed: 12/02/2022]
Abstract
Purpose Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment. Methods The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay. Results The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC. Conclusion MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.
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Gu J, Ni X, Ji J, Wei G, Shi L, Xu C. Efficacy of Apatinib plus S-1 Therapy in the Treatment of Advanced Gastric Cancer Patients and the Effect on the Levels of Tumor Markers and Th1 and Th2-Like Cytokines. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:8060026. [PMID: 35529932 PMCID: PMC9068304 DOI: 10.1155/2022/8060026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/24/2022] [Accepted: 04/16/2022] [Indexed: 12/11/2022]
Abstract
Objective To assess the efficacy of apatinib plus S-1 therapy in the treatment of advanced gastric cancer patients and the effect on the levels of tumor markers and Th1 and Th2-like cytokines. Methods From October 2019 to December 2020, 100 patients with advanced gastric cancer assessed for eligibility were recruited and assigned at a ratio of 1 : 1 to receive either S-1 regimen (tegafur, gimeracil, and oteracil potassium capsules) (observation group) or apatinib plus S-1 therapy (experimental group). Outcome measures included clinical efficacy serum tumor marker levels, Th1 and Th2-like cytokine levels, time to progression (TTP), overall survival (OS), and adverse events. Results The S-1 therapy plus apatinib was associated with a significantly higher efficacy versus S-1 therapy alone (P < 0.05). The eligible patients given S-1 therapy plus apatinib showed significantly lower levels of serum carcinoembryonic antigen (CEA), glycoantigen 199 (CA199), and glycoantigen 125 (CA125) versus those receiving S-1 therapy (P < 0.05). S-1 therapy plus apatinib outperformed the single therapy of S-1 therapy in mitigating the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and interleukin-10 (IL-10) (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). S-1 therapy plus apatinib was associated with a significantly shorter TTP (5.2 ± 0.7 months) and a longer OS (9.3 ± 2.5 months) versus S-1 therapy alone (7.1 ± 1.3, 5.1 ± 1.3 months) (P < 0.05). Conclusion The efficacy of apatinib plus S-1 therapy showed better improvement in lowering the serum tumor marker levels and ameliorating the Th1 and Th2-like cytokine levels versus S-1 therapy alone, so it is worthy of clinical application.
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Affiliation(s)
- Jishu Gu
- Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu 226006, China
| | - Xuejiao Ni
- Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu 226006, China
| | - Jinfeng Ji
- Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu 226006, China
| | - Guohua Wei
- Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu 226006, China
| | - Lei Shi
- Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu 226006, China
| | - Chunming Xu
- Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu 226006, China
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Low Serum miR-607 Level as a Potential Diagnostic and Prognostic Biomarker in Patients of Pancreatic Ductal Adenocarcinoma: A Preliminary Study. Can J Gastroenterol Hepatol 2021; 2021:8882129. [PMID: 34222137 PMCID: PMC8213505 DOI: 10.1155/2021/8882129] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 05/23/2021] [Accepted: 05/29/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND One of the microRNAs (miRNAs) known to be associated with cancer development is miR-607. The aim of this study is to investigate the clinical significance and diagnostic and prognostic value of miR-607 and to explore its potential role in pancreatic ductal adenocarcinoma (PDAC). METHODS The expression levels of miR-607 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between miR-607 expression and clinical characteristics was analyzed by the Chi-square test. Overall survival (OS) and progression-free survival (PFS) were evaluated via the Kaplan-Meier method, and the association between miR-607 expression and OS was investigated by the Cox proportional hazard analysis. The diagnostic value was estimated via receiver operating characteristic (ROC) curve analysis. The effect of miR-607 overexpression on cell migration, invasion, and epithelial-mesenchymal transition (EMT) was determined by wound-healing, Transwell invasion, and Western blotting assays. RESULTS miR-607 levels were downregulated in PDAC tumor tissues compared with normal tissues. Also, low miR-607 levels were observed in serum samples from PDAC patients than that in healthy controls. The miR-607 level was found to be closely correlated with lymphatic metastasis and liver metastasis, perineural invasion, and OS and PFS, and the low miR-607 level was an independent prognostic factor for the poor OS of PDAC patients. Furthermore, the area under the curve (AUC) of serum miR-607 for discriminating PDAC patients was 0.785 with a sensitivity of 0.647 and a specificity of 0.772, which was better than those for CA19-9 (AUC: 0.702, sensitivity: 0.607, specificity: 0.736) and CEA (AUC: 0.648, sensitivity: 0.542, specificity: 0.670). The AUC (0.863), sensitivity (0.766), and specificity (0.831) of their combination in the diagnosis of PDAC were better than those for alone. Moreover, ectopic overexpression of miR-607 could inhibit cell migration and invasion of BxPc-3 and PANC-1 cells by decreasing EMT ability. CONCLUSIONS Low serum miR-607 level may serve as a potential diagnostic and prognostic biomarker through regulation of tumor metastasis in PDAC patients.
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Ouyang J, Xie Z, Lei X, Tang G, Gan R, Yang X. Clinical crosstalk between microRNAs and gastric cancer (Review). Int J Oncol 2021; 58:7. [PMID: 33649806 PMCID: PMC7895535 DOI: 10.3892/ijo.2021.5187] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
Globally, there were over 1 million new gastric cancer (GC) patients in 2018 and GC has become the sixth most common cancer worldwide. GC caused 783,000 deaths worldwide in 2018, making it the third most deadly cancer type. miRNAs are short (~22 nucleotides in length) non‑coding RNA molecules, which can regulate gene expression passively at a post‑transcriptional level. There are more and more in‑depth studies on miRNAs. There are numerous conclusive evidences that there is an inseparable link between miRNAs and GC. miRNAs can affect the entire process of GC, including the oncogenesis, development, diagnosis, treatment and prognosis of GC. Although many miRNAs have been linked to GC, few can be applied to clinical practice. This review takes the clinical changes of GC as a clue and summarizes the miRNAs related to GC that have confirmed the mechanism of action in the past three years. Through in‑depth study and understanding of the mechanism of those miRNAs, we predict their possible clinical uses, and suggest some new insights to overcome GC.
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Affiliation(s)
- Jing Ouyang
- Institute of Pharmacy and Pharmacology, University of South China
| | - Zhizhong Xie
- Institute of Pharmacy and Pharmacology, University of South China
| | - Xiaoyong Lei
- Institute of Pharmacy and Pharmacology, University of South China
| | - Guotao Tang
- Institute of Pharmacy and Pharmacology, University of South China
| | - Runliang Gan
- Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Xiaoyan Yang
- Institute of Pharmacy and Pharmacology, University of South China
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11
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Yang S, Chen B, Zhang B, Li C, Qiu Y, Yang H, Huang Z. miR‑204‑5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER‑2. Mol Med Rep 2020; 22:2645-2654. [PMID: 32945425 PMCID: PMC7453524 DOI: 10.3892/mmr.2020.11367] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 05/20/2020] [Indexed: 12/17/2022] Open
Abstract
Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR‑204‑5p in gastric cancer. The mRNA expression levels of miR‑204‑5p in gastric cancer were determined by reverse transcription‑quantitative PCR. Cell proliferation was determined using Cell Counting Kit‑8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR‑204‑5p in the 3' untranslated region of human epidermal growth factor receptor 2 (HER‑2) was predicted using a bioinformatics algorithm and confirmed using a dual‑luciferase reporter assay. miR‑204‑5p levels were downregulated in gastric cancer cells. Overexpression of miR‑204‑5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR‑204‑5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR‑204‑5p, along with increased expression levels of Bax and decreased expression levels of Bcl‑2. HER‑2 was a direct target of miR‑204‑5p, and inhibition of HER‑2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR‑204‑5p expression. These results suggested that miR‑204‑5p could exert its anti‑tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER‑2, which may be a potential therapeutic target for gastric cancer.
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Affiliation(s)
- Shu Yang
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Binni Chen
- Department of Ophthalmology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Baogen Zhang
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Caiping Li
- Department of Endoscopy Room, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Yuena Qiu
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Hanhui Yang
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Zhongxin Huang
- Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
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12
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Yan Q, Hu D, Li M, Chen Y, Wu X, Ye Q, Wang Z, He L, Zhu J. The Serum MicroRNA Signatures for Pancreatic Cancer Detection and Operability Evaluation. Front Bioeng Biotechnol 2020; 8:379. [PMID: 32411694 PMCID: PMC7201024 DOI: 10.3389/fbioe.2020.00379] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 04/06/2020] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer (PC) has high morbidity and mortality. It is the fourth leading cause of cancer death. Its diagnosis and treatment are difficult. Liquid biopsy makes early diagnosis of pancreatic cancer possible. We analyzed the expression profiles of 2,555 serum miRNAs in 100 pancreatic cancer patients and 150 healthy controls. With advanced feature selection methods, we identified 13 pancreatic cancer signature miRNAs that can classify the pancreatic cancer patients and healthy controls. For pancreatic cancer treatment, operation is still the first choice. But many pancreatic cancer patients are already inoperable. Therefore, we compared the 79 inoperable and 21 operable patients and identified 432 miRNAs that can predict whether a pancreatic cancer patient was operable. The functional analysis of the 13 pancreatic cancer signatures and the 432 operability miRNAs revealed the molecular mechanisms of pancreatic cancer and shield light on the diagnosis and therapy of pancreatic cancer in clinical practice.
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Affiliation(s)
- Qiuliang Yan
- Department of General Surgery, Jinhua People's Hospital, Jinhua, China
| | - Dandan Hu
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Maolan Li
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Chen
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiangsong Wu
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qinghuang Ye
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhijiang Wang
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lingzhe He
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinhui Zhu
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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13
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Baj J, Korona-Głowniak I, Forma A, Maani A, Sitarz E, Rahnama-Hezavah M, Radzikowska E, Portincasa P. Mechanisms of the Epithelial-Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer. Cells 2020; 9:1055. [PMID: 32340207 PMCID: PMC7225971 DOI: 10.3390/cells9041055] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/16/2020] [Accepted: 04/17/2020] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world's population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial-mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial-mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.
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Affiliation(s)
- Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Izabela Korona-Głowniak
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland;
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Amr Maani
- Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Elżbieta Sitarz
- Chair and 1st Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin, Gluska Street 1, 20-439 Lublin, Poland;
| | - Mansur Rahnama-Hezavah
- Chair and Department of Oral Surgery, Medical University of Lublin, 20-081 Lublin, Poland;
| | - Elżbieta Radzikowska
- Department of Plastic Surgery, Central Clinical Hospital of the MSWiA in Warsaw, 01-211 Warsaw, Poland;
| | - Piero Portincasa
- Clinica Medica A. Murri, Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro Medical School, 70126 Bari, Italy;
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14
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林 爱, 卜 文, 汪 萍, 高 继, 杨 建, 丁 飞, 李 铁. [miR-449a/b negatively regulates E2F1 to suppress proliferation of gastric cancer cells]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2020; 40:13-19. [PMID: 32376557 PMCID: PMC7040752 DOI: 10.12122/j.issn.1673-4254.2020.01.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To investigate the possible role of miR-449a/b in the occurrence of gastric cancer. METHODS The expression of miR-449a/b and E2F1 mRNA in gastric cancer cells BGC-823 and gastric mucosal cells GES-1 were detected with qRT-PCR. miR-449a/b mimics or a negative control was transiently transfected into BGC-823 cells, and the changes in cell proliferation, apoptosis, and migration ability were assessed using CCK-8 assay, flow cytometry, and scratch wound healing assay, respectively. Western blotting was used to observe the effects of miR-449a/b upregulation on its target gene expression. The effects of transfection with an E2F1-over-expressing plasmid or an empty plasmid were analyzed on the expression level of miR-449a/b in BGC-823 cells using qRT-PCR and digital PCR. RESULTS The gastric cancer cell line BGC-823 showed significantly a lowered expression of miR-449a/b compared with the normal gastric mucosal cell line GES-1 (P < 0.01). Overexpression of miR-449a/b obviously inhibited the proliferation and migration and promoted apoptosis of BGC-823 cells (P < 0.05). Overexpression E2F1 in the cells resulted in significantly up-regulated expression of miR-449a/b (P < 0.001). Upregulation of miR-449a/b caused significant down-regulation of its direct target genes CDK4 and CDK6 and also of the expression of E2F1 protein via the CDKs-pRb-E2F1 signaling pathway. CONCLUSIONS The low expression of miR-449a/b and the high expression of E2F1 are both involved in the occurrence and progression of gastric cancer, and miR-449a/b negatively regulates E2F1 to inhibit the proliferation of gastric cancer cells.
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Affiliation(s)
- 爱琴 林
- 皖南医学院 医学生物学教研室，安徽 芜湖 241002Department of Medical Biology, Wannan Medical College, Wuhu 241002, China
| | - 文婕 卜
- 皖南医学院 医学生物学教研室，安徽 芜湖 241002Department of Medical Biology, Wannan Medical College, Wuhu 241002, China
| | - 萍 汪
- 皖南医学院 医学生物学教研室，安徽 芜湖 241002Department of Medical Biology, Wannan Medical College, Wuhu 241002, China
| | - 继光 高
- 皖南医学院 医学生物学教研室，安徽 芜湖 241002Department of Medical Biology, Wannan Medical College, Wuhu 241002, China
| | - 建课 杨
- 皖南医学院 医学生物学教研室，安徽 芜湖 241002Department of Medical Biology, Wannan Medical College, Wuhu 241002, China
| | - 飞雨 丁
- 皖南医学院 临床医学院，安徽 芜湖 241002Clinical College of Medicine, Wannan Medical College, Wuhu 241002, China
| | - 铁臣 李
- 皖南医学院 医学生物学教研室，安徽 芜湖 241002Department of Medical Biology, Wannan Medical College, Wuhu 241002, China
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