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Wang Y, Huang D, Li M, Yang M. MicroRNA-99 family in cancer: molecular mechanisms for clinical applications. PeerJ 2025; 13:e19188. [PMID: 40161350 PMCID: PMC11955196 DOI: 10.7717/peerj.19188] [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: 09/16/2024] [Accepted: 02/25/2025] [Indexed: 04/02/2025] Open
Abstract
MicroRNAs (miRNAs) are a class of non-coding RNA sequences that regulate gene expression post-transcriptionally. The miR-99 family, which is highly evolutionarily conserved, comprises three homologs: miR-99a, miR-99b, and miR-100. Its members are under-expressed in most cancerous tissues, suggesting their cancer-repressing properties in multiple cancers; however, in some contexts, they also promote malignant lesion progression. MiR-99 family members target numerous genes involved in various tumor-related processes such as tumorigenesis, proliferation, cell-cycle regulation, apoptosis, invasion, and metastasis. We review the recent research on this family, summarize its implications in cancer, and explore its potential as a biomarker and cancer therapeutic target. This review contributes to the clinical translation of the miR-99 family members.
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Affiliation(s)
- Yueyuan Wang
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, ChangChun, Jilin, China
| | - Dan Huang
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, ChangChun, Jilin, China
| | - Mingxi Li
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, ChangChun, Jilin, China
| | - Ming Yang
- Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, ChangChun, Jilin, China
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Wang C, Chen Z, Ni W, Wang J, Zhou W. Research and progress of microRNA-136 in metastatic tumors. Front Oncol 2025; 15:1555270. [PMID: 40104500 PMCID: PMC11913677 DOI: 10.3389/fonc.2025.1555270] [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: 01/04/2025] [Accepted: 02/11/2025] [Indexed: 03/20/2025] Open
Abstract
Background MiR-136 is abnormally expressed in many types of metastatic tumors and is closely associated with tumor cell proliferation, apoptosis, invasion, and metastasis, indicating its important role in tumor development and progression. This review summarizes current knowledge regarding miR-136's molecular mechanisms, functional roles, and impact on chemotherapy in different human cancers. Methods A literature search was conducted in PubMed and Web of Science using "miR-136" and "metastatic tumors" as English keywords, and in CNKI and Wanfang databases using the same terms in Chinese. Studies related to miR-136 research in metastatic tumors and high-quality evidence from similar studies were included. Meta-analyses, dissertations, conference papers, low-quality articles, unavailable full-text articles, and republished articles were excluded. Results This review synthesizes the current understanding of miR-136's role in various cancers, including osteosarcoma, gastric cancer, gallbladder cancer, esophageal cancer, prostate cancer, colorectal cancer, breast cancer, glioma, and thyroid cancer. miR-136 acts as a tumor suppressor by targeting various genes, including MTDH, PTEN, MAP2K4, MUC1, LRH-1, MIEN1, RASAL2, CYR61, and KLF7. It influences multiple signaling pathways, including the ERK/mitogen-activated protein kinase, Wnt/β-catenin, Ha-Ras, PI3K/Akt, Aurora-A kinase, nuclear factor-κB, and JNK pathways. Furthermore, miR-136 is involved in chemoresistance by modulating ROCK1, PPP2R2A, and the miR-136-Notch3 signaling axis. Conclusions MiR-136 demonstrates promising potential as a novel biomarker and therapeutic target in various human cancers. Further research is needed to fully elucidate its complex roles in cancer development, progression, and drug resistance, particularly regarding its potential in immunotherapy.
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Affiliation(s)
- Chenwen Wang
- Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zixiong Chen
- Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Ni
- Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Jiang Wang
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Zhou
- Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Bagheri M, Akrami H. Studying the non-coding RNA expression and its role in drug resistance mechanisms of gastric cancer. Pathol Res Pract 2025; 265:155742. [PMID: 39602870 DOI: 10.1016/j.prp.2024.155742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 11/23/2024] [Accepted: 11/25/2024] [Indexed: 11/29/2024]
Abstract
Gastric cancer is the fifth most common malignancy and the fifth primary cause of death from cancer all over the world. Because of diagnosis of gastric cancer at advanced, incurable stages and limited response to treatment, the disease has an adverse prognosis and a low survival rate. Chemotherapy consisting of medications such as platinum and 5-Fluorouracil can be effective for patients with advanced stomach cancer. Nevertheless, drug resistance eventually leads to unsuccessful therapy and adverse outcomes for gastric cancer patients. Most therapy failures in gastric cancer patients undergoing chemotherapy are caused by the development of drug resistance. Several studies have shown that noncoding RNAs (ncRNAs) play important roles in the resistance of gastric cancer to chemotherapy drugs. The development of stomach cancer is greatly impacted by a number of ncRNAs, including microRNAs (e.g., miR-21, miR-27a), circular RNAs (e.g., CircPVT1), and long noncoding RNAs (e.g., HOTAIR). Because of their regulatory characteristics in certain genes implicated in the chemoresistant phenotype of gastric cancer, much evidence has demonstrated their function in the emergence and persistence of drug resistance. In the future, ncRNA-based treatment could represent a novel approach to treating drug resistance. Despite numerous studies on anticancer drug resistance mechanisms, it is still unclear how these mechanisms are regulated. In this review, we investigated the evolving function and molecular mechanisms of ncRNAs related to drug resistance, their function in controlling drug resistance in gastric cancer, and their potential to create targeted therapeutics for reducing drug resistance in gastric cancer.
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Affiliation(s)
- Mahdi Bagheri
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hassan Akrami
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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Liu Z, Liu F, Petinrin OO, Wang F, Zhang Y, Wong KC. Uncovering the ceRNA Network Related to the Prognosis of Stomach Adenocarcinoma Among 898 Patient Samples. Biochem Genet 2024; 62:4770-4790. [PMID: 38361095 PMCID: PMC11604743 DOI: 10.1007/s10528-023-10656-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 12/29/2023] [Indexed: 02/17/2024]
Abstract
Stomach adenocarcinoma (STAD) patients are often associated with significantly high mortality rates and poor prognoses worldwide. Among STAD patients, competing endogenous RNAs (ceRNAs) play key roles in regulating one another at the post-transcriptional stage by competing for shared miRNAs. In this study, we aimed to elucidate the roles of lncRNAs in the ceRNA network of STAD, uncovering the molecular biomarkers for target therapy and prognosis. Specifically, a multitude of differentially expressed lncRNAs, miRNAs, and mRNAs (i.e., 898 samples in total) was collected and processed from TCGA. Cytoplasmic lncRNAs were kept for evaluating overall survival (OS) time and constructing the ceRNA network. Differentially expressed mRNAs in the ceRNA network were also investigated for functional and pathological insights. Interestingly, we identified one ceRNA network including 13 lncRNAs, 25 miRNAs, and 9 mRNAs. Among them, 13 RNAs were found related to the patient survival time; their individual risk score can be adopted for prognosis inference. Finally, we constructed a comprehensive ceRNA regulatory network for STAD and developed our own risk-scoring system that can predict the OS time of STAD patients by taking into account the above.
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Affiliation(s)
- Zhe Liu
- Department of Computer Science, City University of Hong Kong, Hong Kong, China
| | - Fang Liu
- College of Chemistry and Chemical Engineering, Central South University, Changsha, China
| | | | - Fuzhou Wang
- Department of Computer Science, City University of Hong Kong, Hong Kong, China
| | - Yu Zhang
- College of Life Sciences, Xinyang Normal University, Xinyang, China
| | - Ka-Chun Wong
- Department of Computer Science, City University of Hong Kong, Hong Kong, China.
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Zhou Y, Li R. Exosomal miR-502-5p suppresses the progression of gastric cancer by repressing angiogenesis through the Wnt/β-catenin pathway. Ir J Med Sci 2024; 193:2681-2694. [PMID: 39325329 DOI: 10.1007/s11845-024-03789-0] [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: 04/30/2024] [Accepted: 08/15/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND Gastric cancer (GC) is a significant global health concern, ranking as the fifth most common cancer and the third leading cause of cancer-related deaths. The role of miR-502-5p in various cancers has been studied, but its specific impact on gastric cancer through exosomes is not well understood. This study aimed to investigate the role and mechanism of exosome-derived miR-502-5p in gastric cancer. METHODS Differential expression of miR-502-5p in tissues or serum of GC patients was determined using qRT-PCR. The impact of miR-502-5p on cell proliferation, migration, and invasion was assessed through in vitro and in vivo experiments. The potential of exosome-miR-502-5p to inhibit metastatic ability was also explored by using vivo and vitro assay. Furthermore, the underlying mechanism of miR-502-5p in gastric cancer was investigated using western blotting. RESULTS It was found that miR-502-5p suppressed the proliferation, migration, and invasion of gastric cancer cells. Exosome-miR-502-5p expression was negatively linked to metastatic ability and demonstrated inhibition of metastasis in vitro and in vivo. Additionally, miR-502-5p appeared to inhibit angiogenesis through the Wnt/β-catenin pathway in gastric cancer. CONCLUSIONS Exosomal miR-502-5p acts as a suppressor in the development and progression of gastric cancer, suggesting its potential as a target for anti-cancer therapy or as a diagnostic biomarker.
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Affiliation(s)
- Yanwu Zhou
- Department of Thoracic Surgery, Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Rong Li
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, People's Republic of China.
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Xu H, Huang K, Shi M, Gong H, Han M, Tian W, Wang X, Zhang D. MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application. Pharmacol Res 2024; 205:107216. [PMID: 38761883 DOI: 10.1016/j.phrs.2024.107216] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 05/20/2024]
Abstract
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
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Affiliation(s)
- Huimei Xu
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Ke Huang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Mingxuan Shi
- Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Hang Gong
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Mengyu Han
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Wenji Tian
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Xiaoying Wang
- Department of Emergency, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
| | - Dekui Zhang
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
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da Silva LM, Martins MR, Dos Santos RL, Da Silva JPA, Lima CAC, Forones NM, Torres LC. Evaluation of soluble co-inhibitors and co-stimulators levels of the immune response in gastric cancer. J Surg Oncol 2024. [PMID: 38946193 DOI: 10.1002/jso.27747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/21/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND Co-inhibitor and co-stimulator mediators trigger actions that result in immunological homeostasis and are being evaluated as potential therapeutic targets in gastric cancer (GC). OBJECTIVE To evaluate the soluble levels of sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL in GC patients. METHODS The cross-sectional study was carried out at the Hospital de Cancer de Pernambuco, Brazil between 2017 and 2018. A total of 74 GC patients and 30 healthy controls were included. RESULTS Low levels of sPD1 (p = 0.0179), sPDL2 (p = 0.0003), and sGal9 (p < 0.0001), and higher levels of sPDL1 (p = 0.004), sTIM-3 (p = 0.0072), sGITR (p = 0.0179), and sGITRL (p = 0.0055) compared to the control group. High sPD-1, sTIM-3, and sGal9 levels in stage IV compared I/II and III (p < 0.05). High sPDL1, sGal9, and sGITRL levels in esophagogastric junction compared to body and Pylorus/Antrum groups (p < 0.05). No significant differences were observed in sPD1, sPDL1, sPDL2, sTIM3, sGal9, sGITR, and sGITRL levels between the intestinal, diffuse, and mixed GC groups. Low sGITR levels in GC patients who died within the first 24 months compared to the who survived (p = 0.0332). CONCLUSIONS There is an association of sPD1, sTIM-3, and sGal9 with disease progression and sGITR with death, these mediators may be potential prognostic biomarkers in GC.
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Affiliation(s)
- Luciana Mata da Silva
- Translational Research Laboratory, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil
- Research Department, Hospital de Câncer de Pernambuco, Recife, Brazil
- Department of Medicine, Postgraduate Program in Translational Medicine, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Mário Rino Martins
- Translational Research Laboratory, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil
- Research Department, Hospital de Câncer de Pernambuco, Recife, Brazil
- Department of Medicine, Postgraduate Program in Translational Medicine, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Rogerio Luiz Dos Santos
- Translational Research Laboratory, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil
- Research Department, Hospital de Câncer de Pernambuco, Recife, Brazil
| | - Jeronimo Paulo Assis Da Silva
- Translational Research Laboratory, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil
- Research Department, Hospital de Câncer de Pernambuco, Recife, Brazil
- Department of Medicine, Postgraduate Program in Translational Medicine, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Cecilia Araujo Carneiro Lima
- Translational Research Laboratory, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil
- Research Department, Hospital de Câncer de Pernambuco, Recife, Brazil
- Department of Medicine, Postgraduate Program in Translational Medicine, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Nora Manoukian Forones
- Department of Digestive Surgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Leuridan Cavalcante Torres
- Translational Research Laboratory, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil
- Research Department, Hospital de Câncer de Pernambuco, Recife, Brazil
- Department of Medicine, Postgraduate Program in Translational Medicine, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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Bhadra M, Sachan M. An overview of challenges associated with exosomal miRNA isolation toward liquid biopsy-based ovarian cancer detection. Heliyon 2024; 10:e30328. [PMID: 38707279 PMCID: PMC11068823 DOI: 10.1016/j.heliyon.2024.e30328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 04/23/2024] [Accepted: 04/23/2024] [Indexed: 05/07/2024] Open
Abstract
As one of the deadliest gynaecological cancers, ovarian cancer has been on the list. With lesser-known symptoms and lack of an accurate detection method, it is still difficult to catch it early. In terms of both the diagnosis and outlook for cancer, liquid biopsy has come a long way with significant advancements. Exosomes, extracellular components commonly shed by cancerous cells, are nucleic acid-rich particles floating in almost all body fluids and hold enormous promise, leading to minimallyinvasive molecular diagnostics. They have been shown as potential biomarkers in liquid biopsy, being implicated in tumour growth and metastasis. In order to address the drawbacks of ovarian cancer tumor heterogeneity, a liquid biopsy-based approach is being investigated by detecting cell-free nucleic acids, particularly non-coding RNAs, having the advantage of being less invasive and more prominent in nature. microRNAs are known to actively contribute to cancer development and their existence inside exosomes has also been made quite apparent which can be leveraged to diagnose and treat the disease. Extraction of miRNAs and exosomes is an arduous execution, and while other approaches have been investigated, none have produced results that are as encouraging due to limits in time commitment, yield, and, most significantly, damage to the exosomal structure resulting discrepancies in miRNA-based expression profiling for disease diagnosis. We have briefly outlined and reviewed the difficulties with exosome isolation techniques and the need for their standardization. The several widely used procedures and their drawbacks in terms of the exosomal purity they may produce have also been outlined.
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Affiliation(s)
- Mridula Bhadra
- Department of Biotechnology, Motilal Nehru National Institute of Technology-Allahabad, Prayagraj, 211004, Uttar Pradesh, India
| | - Manisha Sachan
- Department of Biotechnology, Motilal Nehru National Institute of Technology-Allahabad, Prayagraj, 211004, Uttar Pradesh, India
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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: 2] [Impact Index Per Article: 2.0] [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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Christodoulidis G, Koumarelas KE, Kouliou MN, Thodou E, Samara M. Gastric Cancer in the Era of Epigenetics. Int J Mol Sci 2024; 25:3381. [PMID: 38542354 PMCID: PMC10970362 DOI: 10.3390/ijms25063381] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 03/12/2024] [Accepted: 03/13/2024] [Indexed: 11/11/2024] Open
Abstract
Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein-Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor's metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance.
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Affiliation(s)
- Grigorios Christodoulidis
- Department of General Surgery, University Hospital of Larissa, University of Thessaly, Biopolis Campus, 41110 Larissa, Greece; (G.C.); (K.-E.K.); (M.-N.K.)
| | - Konstantinos-Eleftherios Koumarelas
- Department of General Surgery, University Hospital of Larissa, University of Thessaly, Biopolis Campus, 41110 Larissa, Greece; (G.C.); (K.-E.K.); (M.-N.K.)
| | - Marina-Nektaria Kouliou
- Department of General Surgery, University Hospital of Larissa, University of Thessaly, Biopolis Campus, 41110 Larissa, Greece; (G.C.); (K.-E.K.); (M.-N.K.)
| | - Eleni Thodou
- Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis Campus, 41110 Larissa, Greece;
| | - Maria Samara
- Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis Campus, 41110 Larissa, Greece;
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Akbari A, Noorbakhsh Varnosfaderani SM, Haeri MS, Fathi Z, Aziziyan F, Yousefi Rad A, Zalpoor H, Nabi-Afjadi M, Malekzadegan Y. Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights. Hum Cell 2024; 37:139-153. [PMID: 37924488 DOI: 10.1007/s13577-023-00996-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/11/2023] [Indexed: 11/06/2023]
Abstract
According to the findings of recent research, Helicobacter Pylori (H. pylori) infection is not only the primary cause of gastric cancer (GC), but it is also linked to the spread and invasion of GC through a number of processes and factors that contribute to virulence. In this study, we discussed that H. pylori infection can increase autophagy in GC tumor cells, leading to poor prognosis in such patients. Until now, the main concerns have been focused on H. pylori's role in GC development. According to our hypothesis, however, H. pylori infection may also lead to GC dormancy, metastasis, and recurrence by stimulating autophagy. Therefore, understanding how H. pylori possess these processes through its virulence factors and various microRNAs can open new windows for providing new prevention and/or therapeutic approaches to combat GC dormancy, metastasis, and recurrence which can occur in GC patients with H. pylori infection with targeting autophagy and eradicating H. pylori infection.
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Affiliation(s)
- Abdullatif Akbari
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | | | - Melika Sadat Haeri
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Zeinab Fathi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Aziziyan
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Yousefi Rad
- Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
| | - Hamidreza Zalpoor
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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Chen W, Guo Q, Zhang H, Du Y, Zhou Y, Huang Z, Zhang M, Qin S. Differentially expressed microRNA in prognosis of gastric cancer with Lauren classification. Cancer Biomark 2024; 41:41-54. [PMID: 39177588 PMCID: PMC11492042 DOI: 10.3233/cbm-230303] [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: 08/07/2023] [Accepted: 07/19/2024] [Indexed: 08/24/2024]
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common tumors. There were several classifications of GC recently. The value of Lauren classification in evaluating the prognosis after radical gastrectomy was still unclear and the prognosis of gastric cancer remained relatively poor in the absence of prognostic biomarkers. This study aimed to explore microRNA (miRNA) in the prognosis of GC with different Lauren classification. METHODS A retrospective study of 1144 patients was performed in this study. Quantificational reverse transcription-PCR (qRT-PCR) was used to examine the expression of miRNAs. Univariate and multivariate analysis were performed to evaluate prognosis value of Lauren classification. RESULTS Total 1144 GC patients were recruited in this cohort, including 302 diffuse type (26.4%), 436 intestinal type (38.1%) and 406 mixed type (35.5%) GC. Multivariate analysis showed that Lauren classification, patients' age, tumor size, tumor infiltrating depth, vascular nerve infiltrating and metastatic lymph nodes ration were significantly correlated with GC patients' OS and DFS. The miR-141-3p, miR-200b-3p and miR-133a-5p were significantly down-regulated in diffuse type compared to intestinal type GC tissues, the miR-105-5p had significant lower expression in diffuse type compared with intestinal type and mixed type GC tissues. As a consequence of univariate analysis, low miR-141-3p in diffuse type GC showed significant worse OS and DFS than high miR-141-3p. CONCLUSIONS Lauren classification was an independent prognostic factor in GC. MiR-141-3p was an independent prognostic factor and a promising prognostic biomarker in Lauren classification GC.
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Affiliation(s)
- Wenjiao Chen
- Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Oncology, Affiliated Yixing Hospital of Jiangsu University, Wuxi, China
| | - Qin Guo
- Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Clinical Laboratory, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Huo Zhang
- Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Medical Oncology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Yiping Du
- Department of Oncology, First People’s Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, China
| | - Yan Zhou
- Department of Oncology, Affiliated Yixing Hospital of Jiangsu University, Wuxi, China
| | - Zebo Huang
- Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Meiling Zhang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Songbing Qin
- Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou, China
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Zhu Q, Tan J, Zhan T, Liu M, Zou Y, Liu W. LINC00115 promotes gastric cancer partly by the miR-212-5p/ATPAF1 axis. AN ACAD BRAS CIENC 2023; 95:e20230480. [PMID: 38088732 DOI: 10.1590/0001-3765202320230480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 08/09/2023] [Indexed: 12/18/2023] Open
Abstract
LncRNAs are known to be key regulators in the initiation and development of diverse cancers. Whether LINC00115 is involved in the regulation of gastric cancer (GC) progression remains unclear. Here, we aimed to show the function of LINC00115 in GC. RT-qPCR was used to measure gene expression in GC tissues and cells. Colony formation, EdU, TUNEL, and wound healing assays were used to analyze cellular processes in GC. The in vivo GC xenograft model was established. We observed that LINC00115 was highly expressed in GC. Functionally, silencing LINC00115 inhibited GC cell proliferation, and migration but facilitated GC apoptosis. Mechanistically, LINC00115 sponged miR-212-5p, while miR-212-5p targeted ATPAF1 in GC cells. Rescue assays showed ATPAF1 overexpression countervailed the inhibitory role of LINC00115 depletion in GC progression in vitro and in vivo. Overall, LINC00115 promoted GC progression by upregulating ATPAF1 via miR-212-5p.
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Affiliation(s)
- Qingxi Zhu
- Tongren Hospital of Wuhan University (Wuhan Third Hospital), Department of Gastroenterology, No.241, Pengliuyang Road, Wuhan 430060, Hubei, China
| | - Jie Tan
- Tongren Hospital of Wuhan University (Wuhan Third Hospital), Department of Gastroenterology, No.241, Pengliuyang Road, Wuhan 430060, Hubei, China
| | - Ting Zhan
- Tongren Hospital of Wuhan University (Wuhan Third Hospital), Department of Gastroenterology, No.241, Pengliuyang Road, Wuhan 430060, Hubei, China
| | - Meng Liu
- Tongren Hospital of Wuhan University (Wuhan Third Hospital), Department of Gastroenterology, No.241, Pengliuyang Road, Wuhan 430060, Hubei, China
| | - Yanli Zou
- Tongren Hospital of Wuhan University (Wuhan Third Hospital), Department of Gastroenterology, No.241, Pengliuyang Road, Wuhan 430060, Hubei, China
| | - Weijie Liu
- Tongren Hospital of Wuhan University (Wuhan Third Hospital), Department of Gastroenterology, No.241, Pengliuyang Road, Wuhan 430060, Hubei, China
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Lai TC, Lee CW, Hsu MH, Chen YC, Lin SR, Lin SW, Lee TL, Lin SY, Hsu SH, Tsai JS, Chen YL. Nanocurcumin Reduces High Glucose and Particulate Matter-Induced Endothelial Inflammation: Mitochondrial Function and Involvement of miR-221/222. Int J Nanomedicine 2023; 18:7379-7402. [PMID: 38084125 PMCID: PMC10710795 DOI: 10.2147/ijn.s433658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
Purpose Particulate matter (PM) 2.5, harmful air pollutants, and diabetes are associated with high morbidity and mortality from cardiovascular disease (CVD). However, the molecular mechanisms underlying the combined effects of PM and diabetes on CVD remain unclear. Methods Endothelial cells (ECs) treated with high glucose (HG) and PM mimic hyperglycemia and air pollutant exposure in CVD. Endothelial inflammation was evaluated by Western blot and immunofluorescence of ICAM-1 expression and monocyte adhesion. The mechanisms underlying endothelial inflammation were elucidated through MitoSOX Red analysis, JC-1 staining, MitoTracker analysis, and Western blot analysis of mitochondrial fission-related, autophagy-related, and mitophagy-related proteins. Furthermore. nanocurcumin (NCur) pretreatment was used to test if it has a protective effect. Results ECs under co-exposure to HG and PM increased ICAM-1 expression and monocyte adhesion, whereas NCur pretreatment attenuated these changes and improved endothelial inflammation. PM exposure increased mitochondrial ROS levels, worsened mitochondrial membrane potential, promoted mitochondrial fission, induced mitophagy, and aggravated inflammation in HG-treated ECs, while NCur reversed these changes. Also, HG and PM-induced endothelial inflammation is through the JNK signaling pathway and miR-221/222 specifically targeting ICAM-1 and BNIP3. PM exposure also aggravated mitochondrial ROS levels, mitochondrial fission, mitophagy, and endothelial inflammation in STZ-induced hyperglycemic mice, whereas NCur attenuated these changes. Conclusion This study elucidated the mechanisms underlying HG and PM-induced endothelial inflammation in vitro and in vivo. HG and PM treatment increased mitochondrial ROS, mitochondrial fission, and mitophagy in ECs, whereas NCur reversed these conditions. In addition, miR-221/222 plays a role in the amelioration of endothelial inflammation through targeting Bnip3 and ICAM-1, and NCur pretreatment can modulate miR-221/222 levels. Therefore, NCur may be a promising approach to intervene in diabetes and air pollution-induced CVD.
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Affiliation(s)
- Tsai-Chun Lai
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
- Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China
- The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, Republic of China
| | - Chiang-Wen Lee
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County, Taiwan, Republic of China
- Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County, Taiwan, Republic of China
- Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan City, Taiwan, Republic of China
| | - Mei-Hsiang Hsu
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Yu-Chen Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, Republic of China
| | - Shu-Rung Lin
- Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan, Republic of China
- Center for Nanotechnology and Center for Biomedical Technology, Chung-Yuan Christian University, Taoyuan, Taiwan, Republic of China
| | - Shu-Wha Lin
- Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Tzu-Lin Lee
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Shin-Yu Lin
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China
| | - Shu-Hao Hsu
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Jaw-Shiun Tsai
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
- Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Yuh-Lien Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
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Bilan F, Amini M, Doustvandi MA, Tohidast M, Baghbanzadeh A, Hosseini SS, Mokhtarzadeh A, Baradaran B. Simultaneous suppression of miR-21 and restoration of miR-145 in gastric cancer cells; a promising strategy for inhibition of cell proliferation and migration. BIOIMPACTS : BI 2023; 14:27764. [PMID: 38505672 PMCID: PMC10945301 DOI: 10.34172/bi.2023.27764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 06/13/2023] [Accepted: 06/25/2023] [Indexed: 03/21/2024]
Abstract
Introduction Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. microRNAs are a group of regulatory non-coding RNAs that are involved in GC progression. miR-145 as a tumor suppressor and miR-21 as an oncomiR were shown to be dysregulated in many cancers including GC. This research aimed to enhance the expression of miR-145 while reducing the expression of miR-21 and examine their impact on the proliferation, apoptosis, and migration of GC cells. Methods KATO III cells with high expression levels of miR-21-5p and low expression of miR-145-5p were selected. These cells were then transfected with either miR-145-5p mimics or anti-miR-21-5p, alone or in combination. Afterward, the cell survival rate was determined using the MTT assay, while apoptosis induction was investigated through V-FITC/PI and DAPI staining. Additionally, cell migration was examined using the wound healing assay, and cell cycle progression was analyzed through flow cytometry. Furthermore, gene expression levels were quantified utilizing the qRT-PCR technique. Results The study's findings indicated that the co-replacement of miR-145-5p and anti-miR-21-5p led to a decrease in cell viability and the induction of apoptosis in GC cells. This was achieved via modulating the expression of Bax and Bcl-2, major cell survival regulators. Additionally, the combination therapy significantly increased sub-G1 cell cycle arrest and reduced cell migration by downregulating MMP-9 expression as an epithelial-mesenchymal transition marker. This study provides evidence for the therapeutic possibility of the combination of miR-145-5p and anti-miR-21-5p and also suggests that they could inhibit cell proliferation by modulating the PTEN/AKT1 signaling pathway. Conclusion Our research revealed that utilizing miR-145-5p and anti-miR-21-5p together could be a promising therapeutic approach for treating GC.
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Affiliation(s)
- Farzaneh Bilan
- Department of Biological Science, Faculty of Basic Science, Higher Education Institute of Rab-Rashid, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Maryam Tohidast
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Baghbanzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Zhou Y, Dong Y, Zhang A, Wu J, Sun Q. The role of mesenchymal stem cells derived exosomes as a novel nanobiotechnology target in the diagnosis and treatment of cancer. Front Bioeng Biotechnol 2023; 11:1214190. [PMID: 37662434 PMCID: PMC10470003 DOI: 10.3389/fbioe.2023.1214190] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 08/03/2023] [Indexed: 09/05/2023] Open
Abstract
Mesenchymal stem cells (MSCs), one of the most common types of stem cells, are involved in the modulation of the tumor microenvironment (TME). With the advancement of nanotechnology, exosomes, especially exosomes secreted by MSCs, have been found to play an important role in the initiation and development of tumors. In recent years, nanobiotechnology and bioengineering technology have been gradually developed to detect and identify exosomes for diagnosis and modify exosomes for tumor treatment. Several novel therapeutic strategies bioengineer exosomes to carry drugs, proteins, and RNAs, and further deliver their encapsulated cargoes to cancer cells through the properties of exosomes. The unique properties of exosomes in cancer treatment include targeting, low immunogenicity, flexibility in modification, and high biological barrier permeability. Nevertheless, the current comprehensive understanding of the roles of MSCs and their secreted exosomes in cancer development remain inadequate. It is necessary to better understand/update the mechanism of action of MSCs-secreted exosomes in cancer development, providing insights for better modification of exosomes through bioengineering technology and nanobiotechnology. Therefore, this review focuses on the role of MSCs-secreted exosomes and bioengineered exosomes in the development, progression, diagnosis, and treatment of cancer.
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Affiliation(s)
- You Zhou
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Yuqing Dong
- China Medical University and Department of Pathology, Shenyang, China
| | - Aixue Zhang
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Jibin Wu
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Qiang Sun
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
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17
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Wang HN, Vo-Dinh T. Cascade Amplified Plasmonics Molecular Biosensor for Sensitive Detection of Disease Biomarkers. BIOSENSORS 2023; 13:774. [PMID: 37622860 PMCID: PMC10452163 DOI: 10.3390/bios13080774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/26/2023]
Abstract
Recent advances in molecular technologies have provided various assay strategies for monitoring biomarkers, such as miRNAs for early detection of various diseases and cancers. However, there is still an urgent unmet need to develop practical and accurate miRNA analytical tools that could facilitate the incorporation of miRNA biomarkers into clinical practice and management. In this study, we demonstrate the feasibility of using a cascade amplification method, referred to as the "Cascade Amplification by Recycling Trigger Probe" (CARTP) strategy, to improve the detection sensitivity of the inverse Molecular Sentinel (iMS) nanobiosensor. The iMS nanobiosensor developed in our laboratory is a unique homogeneous multiplex bioassay technique based on surface-enhanced Raman scattering (SERS) detection, and was used to successfully detect miRNAs from clinical samples. The CARTP strategy based on the toehold-mediated strand displacement reaction is triggered by a linear DNA strand, called the "Recycling Trigger Probe" (RTP) strand, to amplify the iMS SERS signal. Herein, by using the CARTP strategy, we show a significantly improved detection sensitivity with the limit of detection (LOD) of 45 fM, which is 100-fold more sensitive than the non-amplified iMS assay used in our previous report. We envision that the further development and optimization of this strategy ultimately will allow multiplexed detection of miRNA biomarkers with ultra-high sensitivity for clinical translation and application.
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Affiliation(s)
- Hsin-Neng Wang
- Fitzpatrick Institute for Photonics, Duke University, Durham, NC 27708, USA;
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA
| | - Tuan Vo-Dinh
- Fitzpatrick Institute for Photonics, Duke University, Durham, NC 27708, USA;
- Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA
- Department of Chemistry, Duke University, Durham, NC 27708, USA
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18
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Pan D, Li Z, Lin X, Li L. Transcriptome sequencing and miRNA-mRNA network construction in exosome of macrophage M2 in stomach adenocarcinoma. World J Surg Oncol 2023; 21:193. [PMID: 37370118 DOI: 10.1186/s12957-023-03070-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 06/11/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Stomach adenocarcinoma (STAD) is the most common histological type of gastric cancer (GC). Macrophages are an essential part of the tumor microenvironment. We attempted to search for potential molecular markers associated with macrophages, which might be helpful for STAD diagnosis and treatment. METHODS Firstly, exosome in macrophages was extracted for RNA sequencing to identify differentially expressed microRNAs (miRNAs) (DEmiRNAs). Then, DEmiRNAs and differentially expressed mRNAs (DEmRNAs) were screened in the Cancer Genome Atlas (TCGA) database. The miRNAs related to macrophage M2 polarization were obtained by intersecting the DEmiRNAs obtained from the sequencing data and TCGA data. Using the Pearson correlation coefficient method, the mRNAs significantly related to macrophage M2 were screened out, followed by construction of the macrophage M2-miRNA-mRNA network. Subsequently, real-time-polymerase chain reaction (RT-PCR) and online datasets were applied to validate the expression of DEmiRNAs and DEmRNAs. RESULTS A total of 6 DEmiRNAs were identified in RNA sequencing; 59 DEmiRNAs and 1838 DEmRNAs were identified in TCGA database. Among which, a common miRNA (hsa-miR-133a-3p) associated with the M2 polarization of macrophages was identified. Fifteen common mRNAs were obtained between DEmRNAs and mRNAs targeted by DEmiRNAs. Eventually, a core macrophage M2-1 down-regulated miRNA-7 and up-regulated mRNAs network was constructed, including hsa-miR-133a-3p, SLC39A1, TTYH3, HAVCR2, TPM3, XPO1, POU2F1, and MMP14. The expression of miRNA and mRNAs was in line with the validation results of RT-PCR and online datasets. CONCLUSION In this study, the screening of biomarkers in exosome of macrophage M2 may contribute to the prognosis of STAD patients.
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Affiliation(s)
- Dun Pan
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China
- Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
- Fujian Research Institute of Abdominal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Zhipeng Li
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China
- Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
- Fujian Research Institute of Abdominal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Xin Lin
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China
- Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
- Fujian Research Institute of Abdominal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Liangqing Li
- Department of Gastrointestinal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.
- Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
- Fujian Research Institute of Abdominal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
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Ju Y, Choi GE, Lee MW, Jeong M, Kwon H, Kim DH, Kim J, Jin H, Lee KE, Hyun KY, Jang A. Identification of miR-143-3p as a diagnostic biomarker in gastric cancer. BMC Med Genomics 2023; 16:135. [PMID: 37328880 PMCID: PMC10273760 DOI: 10.1186/s12920-023-01554-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 05/19/2023] [Indexed: 06/18/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is among the most common types of gastrointestinal cancers and has a high incidence and mortality around the world. To suppress the progression of GC, it is essential to develop diagnostic markers. MicroRNAs regulate GC development, but a clearer insight into their role is needed before they can be applied as a molecular markers and targets. METHODS In this study, we assessed the diagnostic value of differentially expressed microRNAs as potential diagnostic biomarkers for GC using data for 389 tissue samples from the Cancer Genome Atlas (TCGA) and 21 plasma samples from GC patients. RESULTS The expression of hsa-miR-143-3p (also known as hsa-miR-143) was significantly downregulated in GC according to the TCGA data and plasma samples. The 228 potential target genes of hsa-miR-143-3p were analyzed using a bioinformatics tool for miRNA target prediction. The target genes correlated with extracellular matrix organization, the cytoplasm, and identical protein binding. Furthermore, the pathway enrichment analysis of target genes showed that they were involved in pathways in cancer, the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, and proteoglycans in cancer. The hub genes in the protein-protein interaction (PPI) network, were matrix metallopeptidase 2 (MMP2), CD44 molecule (CD44), and SMAD family member 3 (SMAD3). CONCLUSIONS This study suggests that hsa-miR-143-3p may be used as a diagnostic marker for GC, contributing via the pathways involved in the development of GC.
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Affiliation(s)
- Yeongdon Ju
- Medical Science Research Center, Pusan National University, Yangsan, 50612, Republic of Korea
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Go-Eun Choi
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Moon Won Lee
- Division of Gastroenterology, Pusan National University Hospital, Busan, 49241, Republic of Korea
- Department of Internal Medicine, Pusan National University College of Medicine, Busan, 49241, Republic of Korea
| | - Myeongguk Jeong
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Hyeokjin Kwon
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Dong Hyeok Kim
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Jungho Kim
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Hyunwoo Jin
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Kyung Eun Lee
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea
| | - Kyung-Yae Hyun
- Department of Clinical Laboratory Science, Dong-Eui University, Busan, 47340, Republic of Korea.
| | - Aelee Jang
- Department of Nursing, University of Ulsan, Ulsan, 44610, Republic of Korea.
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Li Y, Wang Y, Zou Q, Li S, Zhang F. KLF3 Transcription Activates WNT1 and Promotes the Growth and Metastasis of Gastric Cancer via Activation of the WNT/β-Catenin Signaling Pathway. J Transl Med 2023; 103:100078. [PMID: 36827869 DOI: 10.1016/j.labinv.2023.100078] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/09/2023] [Accepted: 01/24/2023] [Indexed: 02/04/2023] Open
Abstract
The transcription factor Krüppel-like factor (KLF) 3 is one of the members of the KLF family, which plays an important role in tumor progression. Nevertheless, the role of KLF3 in the growth and metastasis of gastric cancer (GC) still needs to be elucidated. Bioinformatics analysis showed that KLF3 was overexpressed in patients with GC, and the high expression of KLF3 was correlated with poor survival. KLF3 was also overexpressed in GC clinical samples and cell lines. In vitro functional role of KLF3 in GC cells was explored by a gain-of-function and loss-of-function assay. Overexpressed KLF3 promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of GC cells, whereas suppressed KLF3 inhibited these biological behaviors. The clinical samples and bioinformatics analysis showed that WNT1 was also highly expressed in GC tumor tissues and positively correlated with KLF3 expression. The luciferase reporter assay and chromatin immunoprecipitation result confirmed that KLF3 could directly bind to the WNT1 promoter to increase the transcriptional activity of WNT1, thus regulating its expression. Overexpressed KLF3 enhanced the protein expression level of p-GSK3β(Ser9) and β-catenin, the key elements in the WNT/β-catenin signaling pathway. Repression of KLF3 decreased the level of p-GSK3β(Ser9) and β-catenin. Immunofluorescence images showed that KLF3 promoted nuclear β-catenin accumulation. Inhibition of WNT1 attenuated the proliferation, migration, and invasiveness of KLF3-overexpressing GC cells. Moreover, the xenograft mouse model confirmed that KLF3 promotes GC tumor growth and metastasis in vivo. Our results demonstrated that KLF3 activates the WNT/β-catenin signaling pathway via WNT1 to promote GC tumor growth and metastasis, indicating that repression of KLF3 may act as a potential therapeutic target for patients with GC.
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Affiliation(s)
- Ying Li
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yu Wang
- Endoscopy Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Qinguang Zou
- Department of Thoracic Surgery, Jilin Cancer Hospital, Changchun, Jilin, China
| | - Shouqing Li
- Tumor Integrative Medicine Center, Jilin Province People's Hospital, Changchun, Jilin, China
| | - Fan Zhang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin, China.
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21
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Wei W, Zhang Y, Yang F, Zhou L, Zhang Y, Wang Y, Yang S, Li J, Dong H. Orthometric multicolor encoded hybridization chain reaction amplifiers for multiplexed microRNA profiling in living cells. Chem Sci 2023; 14:5503-5509. [PMID: 37234881 PMCID: PMC10208064 DOI: 10.1039/d3sc00563a] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 04/19/2023] [Indexed: 05/28/2023] Open
Abstract
Multiplexed microRNA (miRNA) profiling of more than four types in living cells is challenging due to fluorescent spectral overlap, representing a significant limitation in studying the complex interactions related to the occurrence and development of diseases. Herein, we report a multiplexed fluorescent imaging strategy based on an orthometric multicolor encoded hybridization chain reaction amplifier named multi-HCR. The targeting miRNA can trigger this multi-HCR strategy due to the specific sequence recognition, and then its self-assembly to amplify the programmability signals. We take the four-colored chain amplifiers, showing that the multi-HCR can form 15 combinations simultaneously. In a living process of hypoxia-induced apoptosis and autophagy under complicated mitochondria and endoplasmic reticulum stress, the multi-HCR demonstrates excellent performance in detecting eight different miRNA changes. The multi-HCR provides a robust strategy for simultaneously profiling multiplexed miRNA biomarkers in studying complicated cellular processes.
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Affiliation(s)
- Wei Wei
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University 518060 Guangdong China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
- Beijing Yaogen Biotechnology Co. Ltd 26 Yongwangxi Road 102609 Beijing China
| | - Yiyi Zhang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
| | - Fan Yang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
| | - Liping Zhou
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
| | - Yufan Zhang
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University 518060 Guangdong China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
| | - Yeyu Wang
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University 518060 Guangdong China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
- Beijing Yaogen Biotechnology Co. Ltd 26 Yongwangxi Road 102609 Beijing China
| | - Shuangshuang Yang
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University 518060 Guangdong China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
| | - Jinze Li
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University 518060 Guangdong China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
| | - Haifeng Dong
- Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University 518060 Guangdong China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Bioengineering, University of Science and Technology Beijing 30 Xueyuan Road 100083 Beijing China
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22
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Kamarehei F, Saidijam M, Taherkhani A. Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach. Genomics Inform 2023; 21:e8. [PMID: 37037466 PMCID: PMC10085735 DOI: 10.5808/gi.22072] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/02/2023] [Indexed: 04/03/2023] Open
Abstract
Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori–induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori–induced cancer compared with the H. pylori–positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori–induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori–induced GC. However, experimental validation is necessary in the future.
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Affiliation(s)
- Farideh Kamarehei
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran
| | - Massoud Saidijam
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran
| | - Amir Taherkhani
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan 6517838678, Iran
- Corresponding author E-mail:
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23
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Yan W, Chen Y, Hu G, Shi T, Liu X, Li J, Sun L, Qian F, Chen W. MiR-200/183 family-mediated module biomarker for gastric cancer progression: an AI-assisted bioinformatics method with experimental functional survey. J Transl Med 2023; 21:163. [PMID: 36864416 PMCID: PMC9983275 DOI: 10.1186/s12967-023-04010-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 02/18/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is a major cancer burden throughout the world with a high mortality rate. The performance of current predictive and prognostic factors is still limited. Integrated analysis is required for accurate cancer progression predictive biomarker and prognostic biomarkers that help to guide therapy. METHODS An AI-assisted bioinformatics method that combines transcriptomic data and microRNA regulations were used to identify a key miRNA-mediated network module in GC progression. To reveal the module's function, we performed the gene expression analysis in 20 clinical samples by qRT-PCR, prognosis analysis by multi-variable Cox regression model, progression prediction by support vector machine, and in vitro studies to elaborate the roles in GC cells migration and invasion. RESULTS A robust microRNA regulated network module was identified to characterize GC progression, which consisted of seven miR-200/183 family members, five mRNAs and two long non-coding RNAs H19 and CLLU1. Their expression patterns and expression correlation patterns were consistent in public dataset and our cohort. Our findings suggest a two-fold biological potential of the module: GC patients with high-risk score exhibited a poor prognosis (p-value < 0.05) and the model achieved AUCs of 0.90 to predict GC progression in our cohort. In vitro cellular analyses shown that the module could influence the invasion and migration of GC cells. CONCLUSIONS Our strategy which combines AI-assisted bioinformatics method with experimental and clinical validation suggested that the miR-200/183 family-mediated network module as a "pluripotent module", which could be potential marker for GC progression.
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Affiliation(s)
- Wenying Yan
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China. .,Center for Systems Biology, Soochow University, 199 Renai Road, Suzhou, 215123, China.
| | - Yuqi Chen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China
| | - Guang Hu
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China.,Center for Systems Biology, Soochow University, 199 Renai Road, Suzhou, 215123, China
| | - Tongguo Shi
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, 215021, China.,Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, 215021, China.,Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, 215021, China.,Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, 215021, China
| | - Xingyi Liu
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China
| | - Juntao Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China
| | - Linqing Sun
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China
| | - Fuliang Qian
- Center for Systems Biology, Soochow University, 199 Renai Road, Suzhou, 215123, China. .,Medical Center of Soochow University, Suzhou, 215000, China.
| | - Weichang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China. .,Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, 215021, China. .,Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, 215021, China. .,Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, 215021, China. .,Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, 215021, China.
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24
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Farasati Far B, Vakili K, Fathi M, Yaghoobpoor S, Bhia M, Naimi-Jamal MR. The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: A review. Life Sci 2023; 316:121340. [PMID: 36586571 DOI: 10.1016/j.lfs.2022.121340] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/16/2022] [Accepted: 12/26/2022] [Indexed: 12/29/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of several target genes. miRNAs play a significant role in cancer biology, as they can downregulate their corresponding target genes by impeding the translation of mRNA (at the mRNA level) as well as degrading mRNAs by binding to the 3'-untranslated (UTR) regions (at the protein level). miRNAs may be employed as cancer biomarkers. Therefore, miRNAs are widely investigated for early detection of cancers which can lead to improved survival rates and quality of life. This is particularly important in the case of gastrointestinal cancers, where early detection of the disease could substantially impact patients' survival. MicroRNA-21 (miR-21 or miRNA-21) is one of the most frequently researched miRNAs, where it is involved in the pathophysiology of cancer and the downregulation of several tumor suppressor genes. In gastrointestinal cancers, miR-21 regulates phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), mothers against decapentaplegic homolog 7 (SMAD7), phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), matrix metalloproteinases (MMPs), β-catenin, tropomyosin 1, maspin, and ras homolog gene family member B (RHOB). In this review, we investigate the functions of miR-21 in pathogenesis and its applications as a diagnostic and prognostic cancer biomarker in four different gastrointestinal cancers, including colorectal cancer (CRC), pancreatic cancer (PC), gastric cancer (GC), and esophageal cancer (EC).
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Affiliation(s)
- Bahareh Farasati Far
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
| | - Kimia Vakili
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Fathi
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shirin Yaghoobpoor
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammed Bhia
- Student Research Committee, Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Reza Naimi-Jamal
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.
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25
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Chen J, Cai Z, Hu J, Zhou L, Zhang P, Xu X. MicroRNA-375 in extracellular vesicles - novel marker for esophageal cancer diagnosis. Medicine (Baltimore) 2023; 102:e32826. [PMID: 36749234 PMCID: PMC9901947 DOI: 10.1097/md.0000000000032826] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND MicroRNAs have been confirmed to function as diagnostic biomarkers for esophageal cancer (EC). This study aimed to investigate the diagnostic potential of miR-375 in the plasma or extracellular vesicles (EVs) of esophageal cancers (ECs). METHODS miRNAs with diagnostic potential were identified through public database searches and validated through clinical sample testing. The diagnostic value of miR-375 in plasma and EVs was evaluated via receiver operating characteristic analysis and area under the curve. In addition, expression and survival analyses of the top ten target genes of miR-375 were conducted using the cancer genome atlas database. RESULTS MiR-375 was identified as a potential biomarker for ECs by searching the gene expression omnibus database. Results of clinical sample measurements showed that miR-375 in plasma or EVs was significantly different between ECs and controls ( P < .01), but did not differ by gender or age. receiver operating characteristic analysis demonstrated that miR-375 in EVs could function as a diagnostic marker for ECs, with a higher area under the curve (0.852) than that in plasma. The expression and survival analysis of the top ten target genes for miR-375 showed that only EIF4G3 was significantly associated with survival ( P < .05). CONCLUSION This research shows that miR-375, particularly in EVs, could serve as a biomarker for the diagnosis of ECs.
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Affiliation(s)
- Jie Chen
- Department of Thoracic Surgery, The Naval Medical Center of PLA, Second Military Medical University, Shanghai, China
| | - Zhigang Cai
- Department of Thoracic Surgery, The Naval Medical Center of PLA, Second Military Medical University, Shanghai, China
| | - Jing Hu
- Department of Thoracic Surgery, The Naval Medical Center of PLA, Second Military Medical University, Shanghai, China
| | - Lixia Zhou
- Department of Cardiology, The Naval Medical Center of PLA, Second Military Medical University, Shanghai, China
| | - Peili Zhang
- Department of Critical Medicine, The Naval Medical Center of PLA, Second Military Medical University, Shanghai, China
| | - Xiaoping Xu
- Department of Thoracic Surgery, The Naval Medical Center of PLA, Second Military Medical University, Shanghai, China
- * Correspondence: Xiaoping Xu, Department of Thoracic Surgery, the Naval Medical Center of PLA, Second Military Medical University, Shanghai, China (e-mail: )
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26
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Huang Z, Yang X, Huang Y, Tang Z, Chen Y, Liu H, Huang M, Qing L, Li L, Wang Q, Jie Z, Jin X, Jia B. Saliva - a new opportunity for fluid biopsy. Clin Chem Lab Med 2023; 61:4-32. [PMID: 36285724 DOI: 10.1515/cclm-2022-0793] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 09/29/2022] [Indexed: 12/15/2022]
Abstract
Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.
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Affiliation(s)
- Zhijie Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Xiaoxia Yang
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Yisheng Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Zhengming Tang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Yuanxin Chen
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Hongyu Liu
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Mingshu Huang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Ling Qing
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Li Li
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Qin Wang
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Zhuye Jie
- BGI Genomics, BGI-Shenzhen, Shenzhen, P.R. China
- Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, P.R. China
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Xin Jin
- BGI Genomics, BGI-Shenzhen, Shenzhen, P.R. China
- School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Bo Jia
- Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, P.R. China
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27
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Liu Y, Song J, Gu J, Xu S, Wang X, Liu Y. The Role of BTBD7 in Normal Development and Tumor Progression. Technol Cancer Res Treat 2023; 22:15330338231167732. [PMID: 37050886 PMCID: PMC10102955 DOI: 10.1177/15330338231167732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023] Open
Abstract
BTB/POZ domain-containing protein 7 (BTBD7) has a relative molecular weight of 126KD and contains two conserved BTB/POZ protein sequences. BTBD7 has been shown to play an essential role in normal human development, precancerous lesions, heat-stress response, and tumor progression. BTBD7 promotes branching morphogenesis during development and participates in the salivary gland, lung, and tooth formation. Furthermore, many studies have shown that aberrant expression of BTBD7 promotes heat stress response and the progression of precancerous lesions. BTBD7 has also been found to play an important role in cancer. High expression of BTBD7 affects tumor progression by regulating multiple pathways. Therefore, a complete understanding of BTBD7 is crucial for exploring human development and tumor progression. This paper reviews the research progress of BTBD7, which lays a foundation for the application of BTBD7 in regenerative medicine and as a biomarker for tumor prediction or potential therapeutic target.
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Affiliation(s)
- Yun Liu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Jiwu Song
- Weifang People's Hospital, First Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Jianchang Gu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Shuangshuang Xu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Xiaolan Wang
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
| | - Yunxia Liu
- School of Stomatology, Weifang Medical University, Weifang, Shandong, China
- Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
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28
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Masalha M, Meningher T, Mizrahi A, Barzilai A, Tabibian-Keissar H, Gur-Wahnon D, Ben-Dov IZ, Kapenhas J, Jacob-Hirsch J, Leibowitz R, Sidi Y, Avni D. MiR-199a-3p Induces Mesenchymal to Epithelial Transition of Keratinocytes by Targeting RAP2B. Int J Mol Sci 2022; 23:ijms232315401. [PMID: 36499729 PMCID: PMC9741271 DOI: 10.3390/ijms232315401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/27/2022] [Accepted: 11/29/2022] [Indexed: 12/13/2022] Open
Abstract
Cutaneous squamous cell carcinoma (CSCC) is an epidermal skin cancer that evolves from normal epidermis along several pre-malignant stages. Previously we found specific miRNAs alterations in each step along these stages. miR-199a-3p expression decreases at the transition to later stages. A crucial step for epithelial carcinoma cells to acquire invasive capacity is the disruption of cell-cell contacts and the gain of mesenchymal motile phenotype, a process known as epithelial-to-mesenchymal transition (EMT). This study aims to study the role of decreased expression of miR-199a-3p in keratinocytes' EMT towards carcinogenesis. First, we measured miR-199a-3p in different stages of epidermal carcinogenesis. Then, we applied Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) assay to search for possible biochemical targets of miR-199a-3p and verified that Ras-associated protein B2 (RAP2B) is a bona-fide target of miR-199a-3p. Next, we analyzed RAP2B expression, in CSCC biopsies. Last, we evaluated possible mechanisms leading to decreased miR-199a-3p expression. miR-199a-3p induces a mesenchymal to epithelial transition (MET) in CSSC cells. Many of the under-expressed genes in CSCC overexpressing miR-199a-3p, are possible targets of miR-199a-3p and play roles in EMT. RAP2B is a biochemical target of miR-199a-3p. Overexpression of miR-199a-3p in CSCC results in decreased phosphorylated focal adhesion kinase (FAK). In addition, inhibiting FAK phosphorylation inhibits EMT marker genes' expression. In addition, we proved that DNA methylation is part of the mechanism by which miR-199a-3p expression is inhibited. However, it is not by the methylation of miR-199a putative promoter. These findings suggest that miR-199a-3p inhibits the EMT process by targeting RAP2B. Inhibitors of RAP2B or FAK may be effective therapeutic agents for CSCC.
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Affiliation(s)
- Moamen Masalha
- Laboratory of Molecular Cell Biology, Center for Cancer Research, Department of Medicine C, Sheba Medical Center, Tel Hashomer 52621, Israel
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Tal Meningher
- Laboratory of Molecular Cell Biology, Center for Cancer Research, Department of Medicine C, Sheba Medical Center, Tel Hashomer 52621, Israel
| | - Adi Mizrahi
- Laboratory of Molecular Cell Biology, Center for Cancer Research, Department of Medicine C, Sheba Medical Center, Tel Hashomer 52621, Israel
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Aviv Barzilai
- Department of Dermatology, Institute of Pathology Sheba Medical Center, Tel Hashomer 52621, Israel
| | | | - Devorah Gur-Wahnon
- Laboratory of Medical Transcriptomics, Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
| | - Iddo Z. Ben-Dov
- Laboratory of Medical Transcriptomics, Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
| | - Joshua Kapenhas
- Laboratory of Molecular Cell Biology, Center for Cancer Research, Department of Medicine C, Sheba Medical Center, Tel Hashomer 52621, Israel
| | | | - Raya Leibowitz
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
- Oncology institute, Shamir Medical Center, Zerifin 70300, Israel
| | - Yechezkel Sidi
- Laboratory of Molecular Cell Biology, Center for Cancer Research, Department of Medicine C, Sheba Medical Center, Tel Hashomer 52621, Israel
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Dror Avni
- Laboratory of Molecular Cell Biology, Center for Cancer Research, Department of Medicine C, Sheba Medical Center, Tel Hashomer 52621, Israel
- Faculty of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
- Correspondence: ; Tel.: +972-3-5307479
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29
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Joo S, Lee UJ, Son HY, Kim M, Huh YM, Lee TG, Lee M. Highly Selective FRET-Aided Single-Molecule Counting of MicroRNAs Labeled by Splinted Ligation. ACS Sens 2022; 7:3409-3415. [PMID: 36279317 DOI: 10.1021/acssensors.2c01526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in regulating gene expression. Since miRNAs are abnormally expressed in various cancers, they are considered to be promising biomarkers for early cancer diagnosis. However, the short length and strong sequence similarity among miRNAs make their reliable quantification very challenging. We developed a highly selective amplification-free miRNA detection method based on Förster resonance energy transfer (FRET)-aided single-molecule counting. miRNAs were selectively labeled with FRET probes using splinted ligation. When imaged with a single-molecule FRET setup, the miRNA molecules were accurately identified by the probe's FRET. miRNA concentrations were estimated from the count of molecules. The high sensitivity of the method in finding sparse molecules enabled us to achieve a limit of detection of 31-56 amol for miR-125b, miR-100, and miR-99a. Single nucleotide mismatch could be discriminated with a very high target-to-mismatch ratio. The method accurately measured the high expression of miR-125b in gastric cancer cells, which agreed well with previous reports. The high sensitivity and accuracy of this technique demonstrated its clinical potential as a robust miRNA detection method.
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Affiliation(s)
- Sihwa Joo
- Safety Measurement Institute, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, South Korea
| | - Ui Jin Lee
- Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, South Korea
| | - Hye Young Son
- Department of Radiology, College of Medicine, Yonsei University, Seoul 03722, South Korea.,Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul 03722, South Korea
| | - Moonil Kim
- Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, South Korea.,Department of Biotechnology, University of Science and Technology (UST), Daejeon 34113, South Korea
| | - Yong-Min Huh
- Department of Radiology, College of Medicine, Yonsei University, Seoul 03722, South Korea.,Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul 03722, South Korea.,Department of Biochemistry and Molecular Biology, College of Medicine, Yonsei University, Seoul 03722, South Korea.,YUHS-KRIBB Medical Convergence Research Institute, Seoul 03722, South Korea
| | - Tae Geol Lee
- Safety Measurement Institute, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, South Korea.,Department of Nano Science, University of Science and Technology (UST), Daejeon 34113, South Korea
| | - Mina Lee
- Safety Measurement Institute, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, South Korea
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30
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Huang L, Zhang L, Chen X. Updated review of advances in microRNAs and complex diseases: experimental results, databases, webservers and data fusion. Brief Bioinform 2022; 23:6696143. [PMID: 36094095 DOI: 10.1093/bib/bbac397] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/19/2022] [Accepted: 08/15/2022] [Indexed: 12/14/2022] Open
Abstract
MicroRNAs (miRNAs) are gene regulators involved in the pathogenesis of complex diseases such as cancers, and thus serve as potential diagnostic markers and therapeutic targets. The prerequisite for designing effective miRNA therapies is accurate discovery of miRNA-disease associations (MDAs), which has attracted substantial research interests during the last 15 years, as reflected by more than 55 000 related entries available on PubMed. Abundant experimental data gathered from the wealth of literature could effectively support the development of computational models for predicting novel associations. In 2017, Chen et al. published the first-ever comprehensive review on MDA prediction, presenting various relevant databases, 20 representative computational models, and suggestions for building more powerful ones. In the current review, as the continuation of the previous study, we revisit miRNA biogenesis, detection techniques and functions; summarize recent experimental findings related to common miRNA-associated diseases; introduce recent updates of miRNA-relevant databases and novel database releases since 2017, present mainstream webservers and new webserver releases since 2017 and finally elaborate on how fusion of diverse data sources has contributed to accurate MDA prediction.
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Affiliation(s)
- Li Huang
- Academy of Arts and Design, Tsinghua University, Beijing, 10084, China.,The Future Laboratory, Tsinghua University, Beijing, 10084, China
| | - Li Zhang
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, 221116, China
| | - Xing Chen
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, 221116, China.,Artificial Intelligence Research Institute, China University of Mining and Technology, Xuzhou, 221116, China
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31
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Li J, Zhang C, Guo H, Li S, You Y, Zheng P, Zhang H, Wang H, Bai J. Non-invasive measurement of tumor immune microenvironment and prediction of survival and chemotherapeutic benefits from 18F fluorodeoxyglucose PET/CT images in gastric cancer. Front Immunol 2022; 13:1019386. [PMID: 36311742 PMCID: PMC9606753 DOI: 10.3389/fimmu.2022.1019386] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/23/2022] [Indexed: 02/11/2024] Open
Abstract
BACKGROUND The tumor immune microenvironment could provide prognostic and predictive information. It is necessary to develop a noninvasive radiomics-based biomarker of a previously validated tumor immune microenvironment signature of gastric cancer (GC) with immunohistochemistry staining. METHODS A total of 230 patients (training (n = 153) or validation (n = 77) cohort) with gastric cancer were subjected to (Positron Emission Tomography-Computed Tomography) radiomics feature extraction (80 features). A radiomics tumor immune microenvironment score (RTIMS) was developed to predict the tumor immune microenvironment signature with LASSO logistic regression. Furthermore, we evaluated its relation with prognosis and chemotherapy benefits. RESULTS A 8-feature radiomics signature was established and validated (area under the curve=0.692 and 0.713). The RTIMS signature was significantly associated with disease-free survival and overall survival both in the training and validation cohort (all P<0.001). RTIMS was an independent prognostic factor in the Multivariate analysis. Further analysis revealed that high RTIMS patients benefitted from adjuvant chemotherapy (for DFS, stage II: HR 0.208(95% CI 0.061-0.711), p=0.012; stage III: HR 0.321(0.180-0.570), p<0.001, respectively); while there were no benefits from chemotherapy in a low RTIMS patients. CONCLUSION This PET/CT radiomics model provided a promising way to assess the tumor immune microenvironment and to predict clinical outcomes and chemotherapy response. The RTIMS signature could be useful in estimating tumor immune microenvironment and predicting survival and chemotherapy benefit for patients with gastric cancer, when validated by further prospective randomized trials.
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Affiliation(s)
- Junmeng Li
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China
| | - Chao Zhang
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China
| | - Huihui Guo
- Department of Radiology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan, China
| | - Shuang Li
- Department of Pathology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China
| | - Yang You
- Department of Nuclear Medicine, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan, China
| | - Peiming Zheng
- Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China
| | - Hongquan Zhang
- Department of Thoracic Surgery, The First Hospital Affiliated of Xinxiang Medical University, Xinxiang, China
| | - Huanan Wang
- Department of Gastrointestinal Surgery, The First Hospital Affiliated of Zhengzhou University, Zhengzhou, China
| | - Junwei Bai
- Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China
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32
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Babu P, Palaniappan A. miR2Trait: an integrated resource for investigating miRNA-disease associations. PeerJ 2022; 10:e14146. [PMID: 36217386 PMCID: PMC9547587 DOI: 10.7717/peerj.14146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/07/2022] [Indexed: 01/21/2023] Open
Abstract
MicroRNAs are key components of cellular regulatory networks, and breakdown in miRNA function causes cascading effects leading to pathophenotypes. A better understanding of the role of miRNAs in diseases is essential for human health. Here, we have devised a method for comprehensively mapping the associations between miRNAs and diseases by merging on a common key between two curated omics databases. The resulting bidirectional resource, miR2Trait, is more detailed than earlier catalogs, uncovers new relationships, and includes analytical utilities to interrogate and extract knowledge from these datasets. miR2Trait provides resources to compute the disease enrichment of a user-given set of miRNAs and analyze the miRNA profile of a specified diseasome. Reproducible examples demonstrating use-cases for each of these resource components are illustrated. Furthermore we used these tools to construct pairwise miRNA-miRNA and disease-disease enrichment networks, and identified 23 central miRNAs that could underlie major regulatory functions in the human genome. miR2Trait is available as an open-source command-line interface in Python3 (URL: https://github.com/miR2Trait) with a companion wiki documenting the scripts and data resources developed, under MIT license for commercial and non-commercial use. A minimal web-based implementation has been made available at https://sas.sastra.edu/pymir18. Supplementary information is available at: https://doi.org/10.6084/m9.figshare.8288825.v3.
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Affiliation(s)
- Poornima Babu
- Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India
| | - Ashok Palaniappan
- Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India
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33
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Treatment Response Predictors of Neoadjuvant Therapy for Locally Advanced Gastric Cancer: Current Status and Future Perspectives. Biomedicines 2022; 10:biomedicines10071614. [PMID: 35884916 PMCID: PMC9312565 DOI: 10.3390/biomedicines10071614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/01/2022] [Accepted: 07/04/2022] [Indexed: 12/26/2022] Open
Abstract
Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy.
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34
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Genomically Silent Refractory Gastric Cancer in a Young Patient Exhibits Overexpression of CXCL5. Curr Oncol 2022; 29:4725-4733. [PMID: 35877235 PMCID: PMC9320515 DOI: 10.3390/curroncol29070375] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 07/02/2022] [Accepted: 07/05/2022] [Indexed: 12/16/2022] Open
Abstract
Gastric cancer is the third leading cause of cancer-related deaths, with more than one million new cases and approximately 841,000 deaths annually worldwide. We report a case of a young patient (25 years old) with an aggressive form of gastric cancer. The patient had previously been treated for Helicobacter pylori (H. pylori), which is a main risk factor for developing gastric cancer. Genetic testing showed an E-cadherin (CDH1) germline mutation of unknown significance. After eight cycles of chemotherapy, a positron emission tomography (PET) scan showed disease progression with an enlarging hypermetabolic right adnexal mass suspicious for metastatic disease. Tumor pathology demonstrated invasive and poorly differentiated gastric carcinoma. The analysis of the tumor biopsy indicated the very high expression of a chemokine, C-X-C motif chemokine 5 (CXCL5). The combination of H. pylori infection with an existence of a rare CDH1 mutation could have contributed to this aggressive gastric cancer.
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35
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Xu F, Wang Y, Ling Y, Zhou C, Wang H, Teschendorff AE, Zhao Y, Zhao H, He Y, Zhang G, Yang Z. dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms. GENOMICS, PROTEOMICS & BIOINFORMATICS 2022; 20:446-454. [PMID: 35643191 PMCID: PMC9801039 DOI: 10.1016/j.gpb.2022.04.006] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 02/11/2022] [Accepted: 05/08/2022] [Indexed: 01/26/2023]
Abstract
MicroRNAs (miRNAs) are important regulators in gene expression. The dysregulation of miRNA expression is widely reported in the transformation from physiological to pathological states of cells. A large number of differentially expressed miRNAs (DEMs) have been identified in various human cancers by using high-throughput technologies, such as microarray and miRNA-seq. Through mining of published studies with high-throughput experiment information, the database of DEMs in human cancers (dbDEMC) was constructed with the aim of providing a systematic resource for the storage and query of the DEMs. Here we report an update of the dbDEMC to version 3.0, which contains two-fold more data entries than the second version and now includes also data from mice and rats. The dbDEMC 3.0 contains 3268 unique DEMs in 40 different cancer types. The current datasets for differential expression analysis have expanded to 9 generalized categories. Moreover, the current release integrates functional annotations of DEMs obtained by using experimentally validated targets. The annotations can be of great benefit to the intensive analysis of the roles of DEMs in cancer. In summary, dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human cancers. The dbDEMC 3.0 is freely accessible at https://www.biosino.org/dbDEMC.
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Affiliation(s)
- Feng Xu
- Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China; Institutes of Biomedical Science, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Fudan University, Shanghai 200032, China
| | - Yifan Wang
- Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Yunchao Ling
- Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Chenfen Zhou
- Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Haizhou Wang
- Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China; Institutes of Biomedical Science, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Fudan University, Shanghai 200032, China
| | - Andrew E Teschendorff
- CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Yi Zhao
- Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yungang He
- Institutes of Biomedical Science, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Fudan University, Shanghai 200032, China; Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
| | - Guoqing Zhang
- Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
| | - Zhen Yang
- Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China; Institutes of Biomedical Science, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Fudan University, Shanghai 200032, China.
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36
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Helicobacter pylori Infection Mediates Inflammation and Tumorigenesis-Associated Genes Through miR-155-5p: An Integrative Omics and Bioinformatics-Based Investigation. Curr Microbiol 2022; 79:192. [PMID: 35551487 DOI: 10.1007/s00284-022-02880-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 04/15/2022] [Indexed: 11/03/2022]
Abstract
Helicobacter pylori (H. pylori) is a major human pathogenic bacterium that survives in the gastric mucosa. The aim of this study is to evaluate the expression of the target gene network of miR-155-5p in H. pylori-related gastritis using a combination of public gene expression datasets and web-based platforms. To evaluate the expression of genes related to gastritis, we used two datasets from Gene Expression Omnibus (GEO) database. Then, we determined the overlaps between the predicted miR-155-5p target genes and gastritis-dysregulated GEO datasets genes; in the next step, we identified the possible miR-155-5p target-DEGs (Target-Differentially Expressed Genes). Also, we performed multiple bioinformatics analyses to identify the most important targets and downstream pathways associated with this miRNA. Using the UCSC cancer genomic browser analysis tool, we investigated the expression of hub genes in relation to gastric cancer and H. pylori infection, as well as the potential role of hub genes in gastritis, inflammation, and cancer. In this regard, 28 differentially expressed target genes of miR-155-5p were identified. Most of the captured target genes were correlated with the host immune response and inflammation. Based on the specific patterns of expression in gastritis and cancer, CD9, MST1R, and ADAM10 were candidates for the most probable targets of miR-155-5p. Although the focus of this study is primarily on bioinformatics, we think that our findings should be experimentally validated before they can be used as potential therapeutic and diagnostic tools.
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37
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Kahroba H, Samadi N, Mostafazadeh M, Hejazi MS, Sadeghi MR, Hashemzadeh S, Eftekhar Sadat AT, Karimi A. Evaluating the presence of deregulated tumoral onco-microRNAs in serum-derived exosomes of gastric cancer patients as noninvasive diagnostic biomarkers. BIOIMPACTS : BI 2022; 12:127-138. [PMID: 35411299 PMCID: PMC8905585 DOI: 10.34172/bi.2021.22178] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 02/20/2021] [Accepted: 02/27/2021] [Indexed: 12/14/2022]
Abstract
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Introduction: Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for different types of cancers. We aim to detect gastric cancer (GC)-specific miRNAs in serum exosomes with diagnostic potential.
Methods: A pair of 43 tumor and tumor-adjacent tissue biopsies obtained from GC patients, also 5 mL peripheral blood (following 12h fasting) were collected from the same patients and healthy controls (HCs). QIAGEN miRCURY LNA miRNA Focus PCR Panel applied to screen differentially expressed onco-miRNAs. The candidate miRNAs with the highest fold changes proceeded for validation by qRT-PCR in individuals.
Results: We identified that exosomal miR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5p were significantly upregulated in GC patient’s exosomes in contrast to HCs exosomes, Roc curve analysis indicated area under the ROC curve (AUC) of 0.801, 0.721, 0.780 and 0.736 respectively. The Roc curve analysis for the combined signature of four exosomal miRNAs indicated AUC of 0.813. Also, Spearman's correlation coefficients indicated that the miRNA expression is highly correlated between tumor and exosome.
Conclusion: Herein, we specifically identified four miRNAs in serum exosomes of GC patients for a diagnostic purpose which are directly associated with tumoral miRNA expression profile.
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Affiliation(s)
- Houman Kahroba
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nasser Samadi
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mostafa Mostafazadeh
- Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohamad Saied Hejazi
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Reza Sadeghi
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shahryar Hashemzadeh
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Taher Eftekhar Sadat
- Department of General and Vascular Surgery, Imam Reza Educational Hospital, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abbas Karimi
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
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38
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MiR-300 Alleviates Cell Proliferation and Migration and Facilitates Cell Apoptosis by Targeting c-Met in Gastric Cancer. JOURNAL OF ONCOLOGY 2022; 2022:6167554. [PMID: 35419054 PMCID: PMC9001127 DOI: 10.1155/2022/6167554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/21/2022] [Accepted: 02/26/2022] [Indexed: 12/24/2022]
Abstract
c-Met is a potent oncogene, whose aberrant activation has not been fully clarified. In this study, we discover the biological function of miR-300 in gastric cancer (GC) carcinogenesis and the underlying mechanism. The overexpression, oncogenic functions, and survival analysis of c-Met in GC tissues and cells were firstly determined. miRNAs that potentially targets c-Met were then predicted by bioinformatics. The expression levels of candidate miR-300 in GC tissue pairs were investigated. Pearson analysis revealed a negative relation between miR-300 and c-Met expressions. miR-300 and c-Met expression levels were determined in three GC cell lines (MKN-45, SGC-7901, and AGS) as well. Reduced miR-300 led to increase c-Met levels. Luciferase report assay demonstrated a direct binding site of miR-300 in the 3' untranslated region (3′UTR) of c-Met. Finally, the regulatory role of miR-300 on MKN-45 cells was studied by cell proliferation, migration, and apoptosis assays. Overexpression of miR-300 attenuated viability and migration and accelerated apoptosis in MKN-45. We also induced a rescue experiment with c-Met overexpression plasmid and finally proved that miR-300 exerted a suppressing role on MKN-45 proliferation and migration but promoted MKN-45 apoptosis by directly inhibiting c-Met. This study provides a novel insight into the targeted drug development for GC therapies.
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39
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Mechanism of N-Methyl-N-Nitroso-Urea-Induced Gastric Precancerous Lesions in Mice. JOURNAL OF ONCOLOGY 2022; 2022:3780854. [PMID: 35342404 PMCID: PMC8942688 DOI: 10.1155/2022/3780854] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/25/2022] [Accepted: 03/02/2022] [Indexed: 11/17/2022]
Abstract
Early diagnosis and treatment of gastric precancerous lesions (GPL) are key factors for reducing the incidence and morbidity of gastric cancer. The study is aimed at examining GPL in mice induced by N-methyl-N-nitroso-urea (MNU) and to illustrate the underlying mechanisms of tumorigenesis. In this study, we utilized an in vivo MNU-induced GPL mouse model, and histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (H&E-stain) and alcian blue (AB-PAS-stain). The level of miR-194-5p in the gastric mucosa was determined by real-time polymerase chain reaction. We used transmission electron microscopy to observe the effects of MNU on gastric chief cells and parietal cells. We performed immunohistochemical detection of HIF-1α, vWF, Ki-67, and P53, while the changes in the protein expression of key genes in LKB1-AMPK and AKT-FoxO3 signaling pathways were detected by western blot analysis. We demonstrated that the miR-194-5p expression was upregulated under hypoxia in GPL gastric tissues, and that a high miR-194-5p expression level closely related with tumorigenesis. Mechanistically, miR-194-5p exerted the acceleration of activities related to metabolic reprogramming through LKB1-AMPK and AKT-FoxO3 pathways. Furthermore, similar to miR-194-5p, high expression levels of AMPK and AKT were also related to the metabolic reprogramming of GPL. Moreover, we revealed the correlation between the expression levels of miR-194-5p, p-AMPKα, p-AKT, and FoxO3a. These findings suggest that miR-194-5p/FoxO3 pathway is important for the reversal of metabolic reprogramming in GPL. Thus, exploring strategies to regulate the miR-194-5p/FoxO3a pathway may provide an efficient strategy for the prevention and treatment of GPL.
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40
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Mirzajani E, Vahidi S, Norollahi SE, Samadani AA. Novel biomarkers of microRNAs in gastric cancer; an overview from diagnosis to treatment. Microrna 2022; 11:12-24. [PMID: 35319404 DOI: 10.2174/2211536611666220322160242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/06/2021] [Accepted: 12/28/2021] [Indexed: 11/22/2022]
Abstract
The fourth frequent disease in the world and the second cause of cancer-related death is gastric cancer (GC). In this way, over 80% of diagnoses are made in the middle to advanced degrees of the disease, underscoring the requirement for innovative biomarkers that can be identified quickly. Meaningly, biomarkers that can complement endoscopic diagnosis and be used to detect patients with a high risk of GC are desperately needed. These biomarkers will allow for the accurate prediction of therapy response and prognosis in GC patients, as well as the development of an optimal treatment strategy for each individual. Conspicoiusly, microRNAs (miRNAs) and small noncoding RNA regulates the expression of target mRNA and thereby modifies critical biological mechanisms. According to the data, abnormally miRNAs expression in GC is linked to tumor growth, carcinogenesis, aggression and distant metastasis. Importantly, miRNA expression patterns and next-generation sequencing (NGS) can also be applied to analyze kinds of tissues and cancers. Given the high death rates and poor prognosis of GC, and the absence of a clinical diagnostic factor that is adequately sensitive to GC, research into novel sensitive and specific markers for GC diagnosis is critical. In this review,we evaluate the latest research findings that suggest the feasibility and clinical utility of miRNAs in GC.
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Affiliation(s)
- Ebrahim Mirzajani
- Department of Biochemistry, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Sogand Vahidi
- Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Seyedeh Elham Norollahi
- Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Ali Akbar Samadani
- Guilan Road Trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran
- Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
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41
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Liu Y, Li R, Liang F, Deng C, Seidi F, Xiao H. Fluorescent paper-based analytical devices for ultra-sensitive dual-type RNA detections and accurate gastric cancer screening. Biosens Bioelectron 2022; 197:113781. [PMID: 34781178 DOI: 10.1016/j.bios.2021.113781] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 10/29/2021] [Accepted: 11/08/2021] [Indexed: 12/18/2022]
Abstract
Demand on the quick screening of gastric cancer (GC) has significantly stimulated the development of biomarker sensing techniques. Herein, we report the novel fluorescent paper-based analytical devices (PADs) for detections of GC-related microRNA-21 (miRNA-21) and circular RNA from Hippocampus Abundant Transcript 1 gene (circRNA-HIAT1) with prominent reliability and sensitivity. The PADs, constructed by in-situ synthesis of blue-emissive carbon dots (CDs) and conjugations of probe DNAs, exhibit the superior uniformity and stability. In the presence of targets, rolling circle amplifications (RCA) are triggered to generate long DNA strands for the assemblies of green-/red-emissive labels. Consequently, remarkable blue-to-green and blue-to-red emission color transitions of the PADs are achieved, implementing the color-analysis of miRNA-21 and circRNA-HIAT1, respectively. Benefited from the efficient RCA, coupled with the drastic ratiometric fluorescent changes, the limit of detections (LODs) of PADs are found to be several fM with the upper limit of the linear detection range at 1 nM. More importantly, the fluorescent PADs possess excellent specificity, as well as anti-interference capability in biological settings, enabling their applications in accurate GC screening with plasma samples. Overall, the proposed fluorescent PADs are featured with robust sensing platform, facile signal readout, and exceptional dual-type RNA sensing performance, holding high potential in point-of-care testing (POCT).
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Affiliation(s)
- Yuqian Liu
- International Innovation Center for Forest Chemicals and Materials and Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, 210037, China.
| | - Ruyi Li
- International Innovation Center for Forest Chemicals and Materials and Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, 210037, China
| | - Fangyuan Liang
- International Innovation Center for Forest Chemicals and Materials and Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, 210037, China
| | - Chao Deng
- International Innovation Center for Forest Chemicals and Materials and Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, 210037, China
| | - Farzad Seidi
- International Innovation Center for Forest Chemicals and Materials and Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing, 210037, China
| | - Huining Xiao
- Department of Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, E3B5A3, Canada.
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Xu C, Zhou G, Sun Z, Zhang Z, Zhao H, Jiang X. miR-148a-3p inhibits the proliferation and migration of bladder cancer via regulating the expression of ROCK-1. PeerJ 2022; 10:e12724. [PMID: 35127282 PMCID: PMC8800387 DOI: 10.7717/peerj.12724] [Citation(s) in RCA: 7] [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: 03/02/2021] [Accepted: 12/10/2021] [Indexed: 01/12/2023] Open
Abstract
PURPOSE To investigate the mechanism of miR-148a-3p regulating the proliferation and migration of bladder tumor cells. MATERIALS AND METHODS We conducted a preliminary study to detect the relative expression of miR-148a-3p in bladder cancer and para-cancerous tissue samples. Three bladder tumor cell lines, T24, 5,637 and UM-UC-3, were selected. The expression levels of miR-148a-3p were artificially regulated with miR-148a-3p mimics and the miR-148a-3p inhibitor. The relative expression levels of miR-148a-3p in the samples of each cell line were determined. Cell Counting Kit-8 (CCK-8) was used to detect cell proliferation, while the effect of the miR-148a-3p mimics and inhibitor on tumor cell migration was detected by wound healing assay. Flow cytometry assay was carried out to explore the effect of miR-148a-3p on cell apoptosis. Dual-luciferase reporter assay was performed in order to verify miR-148a-3p's target gene. The expressions of ROCK-1 and Bcl-2 were analyzed by western blot. RESULTS The relative expression of miR-148a-3p in tumor and adjacent tissues was assessed with qRT-PCR (P < 0.05) and found to be significantly lower in the tumor tissues than the adjacent tissues. The data obtained from the CCK-8 and wound healing assay showed that intracellular transfection of miR-148a-3p mimics could inhibit cell proliferation and migration, while the miR-148a-3p inhibitor promoted them. Overexpression of miR-148a-3p promoted cell apoptosis in the T24 and 5,637 cell lines. The dual-luciferase reporter assay verified that ROCK-1 is a direct target of miR-148a-3p. Western blot showed that miR-148a-3p overexpression downregulated the expression of ROCK-1 and Bcl-2, while miR-148a-3p knockdown upregulated the expression of ROCK-1 and Bcl-2. CONCLUSIONS We confirmed that miR-148a-3p was significantly decreased in bladder cancer cells. miR-148a-3p overexpression inhibited bladder cancer cell proliferation and migration, whereas miR-148a-3p knockdown promoted bladder cancer cell proliferation and migration. Moreover, we found that ROCK-1 was a downstream target of miR-148a-3p. We also found that miR-148a-3p induced cell apoptosis by regulating the expression of Bcl-2. However, the deeper mechanism of this regulatory relationship needs further study.
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Affiliation(s)
- Chao Xu
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Guanwen Zhou
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhuang Sun
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhaocun Zhang
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Haifeng Zhao
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xianzhou Jiang
- Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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Tang SY, Zhou PJ, Meng Y, Zeng FR, Deng GT. Gastric cancer: An epigenetic view. World J Gastrointest Oncol 2022; 14:90-109. [PMID: 35116105 PMCID: PMC8790429 DOI: 10.4251/wjgo.v14.i1.90] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/17/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) poses a serious threat worldwide with unfavorable prognosis mainly due to late diagnosis and limited therapies. Therefore, precise molecular classification and search for potential targets are required for diagnosis and treatment, as GC is complicated and heterogeneous in nature. Accumulating evidence indicates that epigenetics plays a vital role in gastric carcinogenesis and progression, including histone modifications, DNA methylation and non-coding RNAs. Epigenetic biomarkers and drugs are currently under intensive evaluations to ensure efficient clinical utility in GC. In this review, key epigenetic alterations and related functions and mechanisms are summarized in GC. We focus on integration of existing epigenetic findings in GC for the bench-to-bedside translation of some pivotal epigenetic alterations into clinical practice and also describe the vacant field waiting for investigation.
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Affiliation(s)
- Si-Yuan Tang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Pei-Jun Zhou
- Cancer Research Institute, School of Basic Medicine Science, Central South University, School of Basic Medicine Science, Central South University 410008, Hunan Province, China
| | - Yu Meng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Fu-Rong Zeng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Guang-Tong Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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Zhou Y, Li Z, Wu T, Ning J, Hu G, Nie Y. A DNA–Au nanomachine activated by dual types of biomarkers for multi-site imaging and gene silencing. Chem Commun (Camb) 2022; 58:13107-13110. [DOI: 10.1039/d2cc05017j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
A programmed DNA–Au nanomachine was constructed to achieve in situ imaging of the transmembrane glycoprotein MUC1 and cytoplasmic miRNA-21 and trigger precise gene silencing therapy for breast cancer.
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Affiliation(s)
- Yanmei Zhou
- Henan Joint International Research Laboratory of Environmental Pollution Control Materials, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China
| | - Zhaoge Li
- Henan Joint International Research Laboratory of Environmental Pollution Control Materials, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China
| | - Tian Wu
- Henan Joint International Research Laboratory of Environmental Pollution Control Materials, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China
| | - Juan Ning
- Henan Joint International Research Laboratory of Environmental Pollution Control Materials, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China
| | - Guizhen Hu
- Henan Joint International Research Laboratory of Environmental Pollution Control Materials, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China
| | - Yamin Nie
- Henan Joint International Research Laboratory of Environmental Pollution Control Materials, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China
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Wei C, Jiang P, Li G, Li M, Wang L. 5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone up-regulates miR-145 expression and inhibits proliferation of gastric cancer cells. Arch Med Sci 2022; 18:753-760. [PMID: 35591840 PMCID: PMC9103526 DOI: 10.5114/aoms/121038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 04/25/2020] [Indexed: 01/19/2023] Open
Abstract
INTRODUCTION Gastric cancer is a frequently detected malignancy, and its incidence has increased over the past decades in East Asia. The present study investigated the effect of 5,7,2, 5-tetrahydroxy-8,6-dimethoxyflavone (THDMF) on gastric cancer cells and explored the underlying mechanism. The study analysed cell viability changes, apoptotic features, and metastasis potential of treatment with THDMF. MATERIAL AND METHODS MTT colorimetric assay was used for measurement of MKN28, MKN45, and GES-1 cell proliferation and flow cytometry for the detection of apoptosis. Transwell and wound healing assays were used to observe the invasion and migration abilities of MKN28 cells. The expression of p21, MMP2/-9, PI3K, and c-Myc proteins was detected by western blotting. RESULTS The THDMF treatment significantly (p < 0.05) reduced MKN28 and MKN45 cell proliferation without changing GES-1 cell viability. A significant increase in apoptotic cell population on treatment with THDMF was observed. Treatment of MKN28 cells with THDMF increased the percentage of cells in the G1 phase. Exposure of MKN28 cells to THDMF caused a marked decrease in invasion and migration potential in comparison to control cells. The expression of miR-145 was markedly increased in MKN28 cells on treatment with THDMF. In MKN28 cells expression of c-Myc, PI3K, p-AKT, MMP-2, and MMP-9 was suppressed markedly on exposure to THDMF. The expression of p21 protein in MKN28 cells was markedly promoted on exposure to THDMF. CONCLUSIONS THDMF exhibits anti-cancer effect on gastric cancer cells in vitro by activation of cell apoptosis and arrest of cell cycle. In addition, THDMF promoted miR-145 expression and down-regulation of PI3K/AKT signalling pathway in MKN28 cells. Therefore, THDMF may be utilised as a potential novel therapeutic agent for the treatment of gastric cancer.
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Affiliation(s)
- Chunhong Wei
- Department of Oncology, Second People’s Hospital of Dezhou, Decheng District, Dezhou, Shandong Province, China
| | - Peng Jiang
- Department of Endoscopic, Second People’s Hospital of Dezhou, Decheng District, Dezhou, Shandong Province, China
| | - Guangxu Li
- Department of Thoracic Surgery, Second People’s Hospital of Dezhou, Decheng District, Dezhou, Shandong Province, China
| | - Meng Li
- Department of Gastrointestinal Surgery, Second People’s Hospital of Dezhou, Decheng District, Dezhou, Shandong Province, China
| | - Li Wang
- Department of Oncology, Second People’s Hospital of Dezhou, Decheng District, Dezhou, Shandong Province, China
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Saliminejad K, Mahmoodzadeh H, Soleymani Fard S, Yaghmaie M, Khorram Khorshid HR, Mousavi SA, Vaezi M, Ghaffari SH. A Panel of Circulating microRNAs as a Potential Biomarker for the Early Detection of Gastric Cancer. Avicenna J Med Biotechnol 2022; 14:278-286. [PMID: 36504565 PMCID: PMC9706247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 07/02/2022] [Indexed: 12/15/2022] Open
Abstract
Background The high mortality rate of Gastric Cancer (GC) is a consequence of delayed diagnosis. The early diagnosis of GC could increase the five-year survival rate among patients. We aimed to find a panel of microRNAs (miRNA) for the detection of GC in the early stages. Methods In this case-control study, we selected consistently upregulated miRNAs from the results of 12 high-throughput miRNA profiling studies in GC. In the profiling phase, the differential expressions of 13 candidate miRNAs were analyzed by quantitative reverse-transcription PCR (qRT-PCR) in two pooled RNA samples prepared from the plasma of eight GC patients and eight matched controls. In the validation phase, significantly upregulated miRNAs from the profiling phase were further evaluated in the plasma samples of 97 patients with stage I-IV gastric adenocarcinoma and 100 healthy controls. Results In the profiling phase, six miRNAs (miR-18a, 21, 25, 92a, 125b and 221) were significantly upregulated in the GC patients compared to the controls (p<0.05). However, in the validation phase, only significant up-regulation of miR-18a, 21 and 125b was confirmed (p<0.05). A panel of miR-18a/21/125b was able to detect GC patients with stage I-IV from the controls (p<0.001; AUC=0.92, sensitivity=86%; specificity=85%). In addition, the panel could distinguish the early-stage GC (I+II) from the control group with an AUC of 0.83, a sensitivity of 83%, and a specificity of 75%. Conclusion A panel of circulating miR18a/21/125b could be suggested as a potential biomarker for the early detection of GC.
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Affiliation(s)
- Kioomars Saliminejad
- Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Habibollah Mahmoodzadeh
- Department of Surgery, Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahrzad Soleymani Fard
- Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Marjan Yaghmaie
- Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Seyed Asadollah Mousavi
- Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Vaezi
- Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Hamidollah Ghaffari
- Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran,Corresponding author: Seyed Hamidollah Ghaffari, Ph.D., Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, Tel: +98 21 84902665, Fax: +98 21 88004140, E-mail:,
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Di Giorgio C, Marchianò S, Marino E, Biagioli M, Roselli R, Bordoni M, Bellini R, Urbani G, Zampella A, Distrutti E, Donini A, Graziosi L, Fiorucci S. Next-Generation Sequencing Analysis of Gastric Cancer Identifies the Leukemia Inhibitory Factor Receptor as a Driving Factor in Gastric Cancer Progression and as a Predictor of Poor Prognosis. Front Oncol 2022; 12:939969. [PMID: 35847866 PMCID: PMC9280277 DOI: 10.3389/fonc.2022.939969] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/30/2022] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is the third cause of cancer-related mortality worldwide. Nevertheless, because GC screening programs are not cost-effective, most patients receive diagnosis in the advanced stages, when surgical options are limited. Peritoneal dissemination occurs in approximately one-third of patients with GC at the diagnosis and is a strong predictor of poor outcome. Despite the clinical relevance, biological and molecular mechanisms underlying the development of peritoneal metastasis in GC remain poorly defined. Here, we report results of a high-throughput sequencing of transcriptome expression in paired samples of non-neoplastic and neoplastic gastric samples from 31 patients with GC with or without peritoneal carcinomatosis. The RNA-seq analysis led to the discovery of a group of highly upregulated or downregulated genes, including the leukemia inhibitory factor receptor (LIFR) and one cut domain family member 2 (ONECUT2) that were differentially modulated in patients with peritoneal disease in comparison with patients without peritoneal involvement. Both LIFR and ONECUT2 predicted survival at univariate statistical analysis. LIFR and its major ligand LIF belong to the interleukin-6 (IL-6) cytokine family and have a central role in immune system regulation, carcinogenesis, and dissemination in several human cancers. To confirm the mechanistic role of the LIF/LIFR pathway in promoting GC progression, GC cell lines were challenged in vitro with LIF and a LIFR inhibitor. Among several GC cell lines, MKN45 cells displayed the higher expression of the receptor, and their exposure to LIF promotes a concentration-dependent proliferation and epithelial-mesenchymal transition (EMT), as shown by modulation of relative expression of E-cadherin/vimentin along with JAK and STAT3 phosphorylation and acquisition of a migratory phenotype. Furthermore, exposure to LIF promoted the adhesion of MKN45 cells to the peritoneum in an ex vivo assay. These effects were reversed by the pharmacological blockade of LIFR signaling. Together, these data suggest that LIFR might have a major role in promoting disease progression and peritoneal dissemination in patients with GC and that development of LIF/LIFR inhibitors might have a role in the treatment of GC.
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Affiliation(s)
| | - Silvia Marchianò
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | | | - Michele Biagioli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Rosalinda Roselli
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Martina Bordoni
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Rachele Bellini
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Ginevra Urbani
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Angela Zampella
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | | | - Annibale Donini
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Luigina Graziosi
- Azienda Ospedaliera Santa Maria della Misericordia, Perugia, Italy
| | - Stefano Fiorucci
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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Yang C, Deng S. Hsa_circ_0017728 as an oncogene in gastric cancer by sponging miR-149 and modulating the IL-6/STAT3 pathway. Arch Med Sci 2022; 18:1558-1571. [PMID: 36457988 PMCID: PMC9710264 DOI: 10.5114/aoms.2019.87274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Accepted: 06/03/2019] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Circular RNAs (circRNAs) have been identified as competing endogenous RNAs (ceRNAs) to mediate gene expression participating in the progression of multiple cancers, including gastric carcinoma (GC). However, the underlying molecular mechanisms by which circRNAs-modulated cell proliferation and apoptosis in GC had not been completely clarified. In our study, hsa_circ_0017728 as a potential oncogene competing endogenous RNA (ceRNA) was investigated in the progression and development of gastric carcinogenesis. MATERIAL AND METHODS High-throughput sequencing was used to determine differentially expressed circRNAs in GC tissues and corresponding non-cancerous tissues. The CCK-8 assay and Annexin V-fluorescein isothiocyanate/polyimide (Annexin V-FITC/PI) staining were performed to detect the cell viability and apoptosis in GC cells. In addition, gene expression and protein levels in GC tissues and cell lines were measured using RT-qPCR and western blotting, respectively. RESULTS Our results demonstrated that the hsa_circ_0017728 expression level was up-regulated in GC tissues and cell lines and closely associated with poor overall survival and pathological differentiation, higher TNM stage and lymph node metastasis. Knockdown of hsa_circ_0017728 had the ability to cause inhibition of cell proliferation and migration and elevate the cell apoptosis rate in GC cells. We also discovered that hsa_circ_0017728 might serve as a ceRNA to sponge miR-149 and indirectly regulated the IL-6/STAT3 signaling pathway in GC cell proliferation and apoptosis. CONCLUSIONS The regulatory network of hsa_circ_0017728/miR-149/IL-6/STAT3 cascade signaling might provide a better understanding of gastric carcinogenesis and progression.
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Affiliation(s)
- Chun Yang
- School of Medicine, University of Electronic Science and Technology of China; Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
| | - Shaoping Deng
- School of Medicine, University of Electronic Science and Technology of China; Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China
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Zhao LX, Zhang K, Shen BB, Li JN. Mesenchymal stem cell-derived exosomes for gastrointestinal cancer. World J Gastrointest Oncol 2021; 13:1981-1996. [PMID: 35070036 PMCID: PMC8713327 DOI: 10.4251/wjgo.v13.i12.1981] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/15/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) malignancies, a series of malignant conditions originating from the digestive system, include gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. GI cancers have been regarded as the leading cancer-related cause of death in recent years. Therefore, it is essential to develop effective treatment strategies for GI malignancies. Mesenchymal stem cells (MSCs), a type of distinct non-hematopoietic stem cells and an important component of the tumor microenvironment, play important roles in regulating GI cancer development and progression through multiple mechanisms, such as secreting cytokines and direct interactions. Currently, studies are focusing on the anti-cancer effect of MSCs on GI malignancies. However, the effects and functional mechanisms of MSC-derived exosomes on GI cancer are less studied. MSC-derived exosomes can regulate GI tumor growth, drug response, metastasis, and invasion through transplanting proteins and miRNA to tumor cells to activate the specific signal pathway. Besides, the MSC-derived exosomes are also seen as an important drug delivery system and have shown potential in anti-cancer treatment. This study aims to summarize the effect and biological functions of MSC-derived exosomes on the development of GI cancers and discuss their possible clinical applications for the treatment of GI malignancies.
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Affiliation(s)
- Lin-Xian Zhao
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Bing-Bing Shen
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Jian-Nan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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Wei S, Dai S, Zhang C, Zhao R, Zhao Z, Song Y, Shan B, Zhao L. LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex. Front Oncol 2021; 11:721604. [PMID: 34900675 PMCID: PMC8660099 DOI: 10.3389/fonc.2021.721604] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 10/20/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) have been reported to be the important regulators during the occurrence and development of GC. The present study identified a novel and functional lncRNA in GC, named NR038975, which was confirmed to be markedly upregulated in the Gene Expression Profiling Interactive Analysis (GEPIA) dataset and our independent cohort of GC tissues. We firstly characterized the full-length sequence and subcellular location of NR038975 in GC cells. Our data demonstrated that upregulated NR038975 expression was significantly related to lymph node metastasis and TNM stage. In addition, knockdown of NR038975 inhibited GC cell proliferation, migration, invasion, and clonogenicity and vice versa. Mechanistically, RNA pull-down and mass spectrometry assays identified the NR038975-binding proteins and NF90/NF45 complex, and the binding was also confirmed by RNA immunoprecipitation and confocal experiments. We further demonstrated that genetic deficiency of NR038975 abrogated the interaction between NF45 and NF90. Moreover, NF90 increased the stability of NR038975. Thus, NR038975-NF90/NF45 will be an important combinational target of GC. Finally, we detected NR038975 in serum exosomes and serum of GC patients. Our results indicated that NR038975 was a biomarker for gastric tumorigenesis. The current study demonstrated that NR038975 is a novel lncRNA that is clinically and functionally engaged in GC progression and might be a novel diagnostic marker and potential therapeutic target.
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Affiliation(s)
- Sisi Wei
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Suli Dai
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Cong Zhang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ruinian Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zitong Zhao
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongmei Song
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Baoen Shan
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lianmei Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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