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Gu C, ChenLiu Z, Wu Q, Tang D. ncRNAs as Key Regulators in Gastric Cancer: From Molecular Subtyping to Therapeutic Targets. Ann Surg Oncol 2025:10.1245/s10434-025-17368-9. [PMID: 40358781 DOI: 10.1245/s10434-025-17368-9] [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: 02/20/2025] [Accepted: 04/08/2025] [Indexed: 05/15/2025]
Abstract
Gastric cancer (GC) poses a major global health challenge, underscoring the need for advanced diagnostic and therapeutic approaches. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators in GC, with their dysregulated expression driving key processes such as tumorigenesis, metastasis, immune evasion, and chemoresistance. The functional diversity of ncRNAs across different GC molecular subtypes highlights their potential as biomarkers for improved subtype classification and patient stratification. Beyond their diagnostic value, ncRNAs demonstrate critical regulatory functions in tumor biology, establishing these RNA molecules as promising targets for therapeutic development. Strategies based on RNA hold considerable promise for addressing critical challenges such as immune escape and drug resistance by modulating key signaling pathways. These approaches can enhance immune responses, reprogram the tumor microenvironment, and reverse resistance mechanisms that compromise treatment efficacy, thereby improving clinical outcomes. Although ncRNAs represent a promising frontier in GC precision medicine, further research is required to fully harness their clinical potential.
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Affiliation(s)
- Chen Gu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Zhenni ChenLiu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Qihang Wu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Yangzhou, China.
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Xuzhou Medical University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Dalian Medical University, Dalian Medical University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Nanjing Medical University, Yangzhou, China.
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2
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Mansour RM, El-Sayyad GS, Abulsoud AI, Hemdan M, Faraag AHI, Ali MA, Elsakka EGE, Abdelmaksoud NM, Abdallah AK, Mahdy A, Ashraf A, Zaki MB, Elrebehy MA, Mohammed OA, Abdel-Reheim MA, Abdel Mageed SS, Alam Eldein KM, Doghish AS. The role of miRNAs in pathogenesis, diagnosis, and therapy of Helicobacter pylori infection, gastric cancer-causing bacteria: Special highlights on nanotechnology-based therapy. Microb Pathog 2025; 205:107646. [PMID: 40348207 DOI: 10.1016/j.micpath.2025.107646] [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: 02/13/2025] [Revised: 04/24/2025] [Accepted: 04/28/2025] [Indexed: 05/14/2025]
Abstract
Helicobacter pylori (H. pylori) infection and consequent inflammation in the stomach are widely recognized as major contributors to gastric cancer (GC) development. Recent investigations have placed considerable emphasis on uncovering the controlling influence of small RNA molecules known as microRNAs (miRNAs) in H. pylori-related diseases, particularly gastric cancer. This review aims to offer a comprehensive understanding of the intricate roles fulfilled by miRNAs in conditions associated with H. pylori infection. Exploring miRNA biogenesis pathways reveals their intimate connection with H. pylori infection, shedding light on the underlying molecular mechanisms driving disease progression and identifying potential intervention targets. An examination of epidemiological data surrounding H. pylori infection, including prevalence, risk factors, and transmission routes, underscores the imperative for preventive measures and targeted interventions. Incorporating insights from miRNA-related research into these strategies holds promise for enhancing their efficacy in controlling H. pylori spread. The symptoms, underlying mechanisms, and virulent characteristics of the bacteria highlight the intricate relationship between H. pylori and host cells, influencing the course of diseases. Within this complex web, miRNAs play pivotal roles, regulating various facets of H. pylori's development. MicroRNAs intricately involved in directing the immune response against H. pylori infection serve as key players in molding host defense mechanisms and impacting the bacterium's evasion tactics. Utilizing this knowledge holds the potential to drive forward groundbreaking therapeutic strategies. The diagnostic and prognostic capabilities of miRNAs in H. pylori infection highlight their effectiveness as non-invasive indicators for identifying diseases and evaluating risk. Integration of miRNA signatures into diagnostic algorithms holds promise for enhancing early detection and management of H. pylori-related diseases. MiRNA-based therapeutics offer a promising avenue for combatting H. pylori-induced gastric cancer, targeting specific molecular pathways implicated in tumorigenesis. H. pylori infection induces dysregulation of several miRNAs that contribute to antibiotic resistance, inflammation, and gastric cancer progression, including downregulation of tumor-suppressive miR-7 and miR-153 and upregulation of oncogenic miR-671-5p and miR-155-5p, which promote carcinogenesis and inflammation. Additionally, H. pylori manipulates host immune responses by upregulating miRNAs such as let-7f-5p, let-7i-5p, miR-146b-5p, and miR-185-5p that suppress HLA class II expression and antigen presentation, facilitating immune evasion and chronic gastritis that predispose to gastric cancer. Future research endeavors should focus on refining these therapeutic modalities and identifying novel targets to optimize clinical outcomes. By elucidating the multifaceted roles of miRNAs in H. pylori infection, this review provides invaluable insights into disease pathogenesis, diagnostics, and therapeutics, and the role of some nanoparticles in combating the H. pylori infection. Continued research efforts are imperative for translating these insights into clinical practice and addressing the global burden of H. pylori-related diseases.
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Affiliation(s)
- Reda M Mansour
- Zoology and Entomology Department, Faculty of Science, Helwan University, Helwan, 11795, Egypt; Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Gharieb S El-Sayyad
- Department of Medical Analysis Technology, Faculty of Applied Health Sciences Technology, Badr University in Cairo (BUC), Cairo, Egypt; Drug Microbiology Lab., Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, Egypt.
| | - Mohamed Hemdan
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Ahmed H I Faraag
- Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, 11795, Egypt; Medical Department, School of Biotechnology, Badr University in Cairo, Badr City, Cairo, 11829, Egypt.
| | - Mohamed A Ali
- School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt.
| | - Nourhan M Abdelmaksoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, Egypt.
| | - Asmaa K Abdallah
- Botany and Microbiology Department, Faculty of Science, Benha University, 13518 Benha, Egypt.
| | - Ahmed Mahdy
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Alaa Ashraf
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Mohamed Bakr Zaki
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia, 32897, Egypt; Department of Biochemistry, Faculty of Pharmacy, Menoufia National University, km Cairo-Alexandria Agricultural Road, Menofia, Egypt.
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Galala University, New Galala City, 43713, Suez, Egypt.
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
| | | | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Khaled M Alam Eldein
- Molecular Biology and Biotechnology Department, School of Biotechnology, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Ahmed S Doghish
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt; Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
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3
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Rai RP, Syed A, Elgorban AM, Abid I, Wong LS, Khan MS, Khatoon J, Prasad KN, Ghoshal UC. Expressions of selected microRNAs in gastric cancer patients and their association with Helicobacter pylori and its cag pathogenicity island. Microb Pathog 2025; 202:107442. [PMID: 40049249 DOI: 10.1016/j.micpath.2025.107442] [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: 07/11/2024] [Revised: 02/24/2025] [Accepted: 02/28/2025] [Indexed: 03/12/2025]
Abstract
BACKGROUND Helicobacter pylori infection and the resulting inflammation of the stomach are widely recognized as the primary risk factors for the development of gastric cancer (human health). Despite numerous attempts, the correlation between various virulence factors of H. pylori and stomach cancer remains mainly unexplained. The cag pathogenicity island (cagPAI) is a widely recognized indicator of virulence in H. pylori. MicroRNAs play crucial roles in a wide range of biological and pathological processes and dysregulated expressions of miRNAs have been detected in numerous cancer types. However, research on the correlation between H. pylori infection and its cagPAI, as well as the differential expression of microRNAs in gastric cancer, is lacking. AIM The aim of this study was to examine the differential expression of miRNAs in 80 patients with gastric cancer, specifically in connection to the presence of H. pylori and its cag pathogenicity island (cagPAI). METHODS Biopsies of 80 gastric cancer patients were collected and used for H. pylori DNA isolation and tissue miRNA isolation, and further analyzed for cagPAI and miRNA expression and their association. RESULTS Elevated levels of miR-21, miR-155, and miR-223 were detected in malignant tissues. The expression of miR-21 and miR-223 was considerably elevated in biopsies that tested positive for H. pylori, whereas the expression of miR-34a was reduced. H. pylori cagPAI samples that are functionally intact exhibit greater expression of miR-21 and miR-223 compared to cagPAI samples that are partially deleted, in both normal and malignant tissues. CONCLUSION Thus, the novelty of our study lies in its focus on the differential expression of specific miRNAs in relation to the functional integrity of the cagPAI in H. pylori-infected gastric cancer patients, offering a more detailed understanding of the interplay between H. pylori virulence factors and miRNA regulation than previous studies.
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Affiliation(s)
- Ravi Prakash Rai
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Asad Syed
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
| | - Abdallah M Elgorban
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Islem Abid
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Putra Nilai, 71800, Nilai, Negeri Sembilan, Malaysia.
| | - Mohd Sajid Khan
- Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Jahanarah Khatoon
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Kashi N Prasad
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, Lucknow, India.
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Tavares I, Morais M, Dias F, Ferreira M, Martins G, Fernandes R, Bidarra SJ, Medeiros R, Teixeira AL. Extracellular vesicles derived-microRNAs predicting enzalutamide-resistance in 3D spheroid prostate Cancer model. Int J Biol Macromol 2025; 284:137993. [PMID: 39592052 DOI: 10.1016/j.ijbiomac.2024.137993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 11/19/2024] [Accepted: 11/21/2024] [Indexed: 11/28/2024]
Abstract
Enzalutamide (ENZ) has emerged as a major treatment advance in castration-resistant prostate cancer (CRPC) patients; however the development of resistance remains a key challenge. The extracellular vesicles (VEs)-derived miRNAs play crucial roles tumor microenvironment cell communication, thereby influencing resistance mechanisms. Considering the urgent need for molecular biomarkers to monitor ENZ response and predict resistance, we intend to identify an EV-derived miRNA profile associated with ENZ resistance using an innovative 3D-spheroid in vitro model. Through the generation of this model, we provide a comprehensive platform for elucidating the molecular alterations involved in the process. An in vitro model of ENZ resistance was established through continuous exposure of LNCaP to increasing ENZ concentrations. A screening of 799 miRNAs from resistant and normal LNCaP cells were quantified. A bioinformatic analysis was performed using miRTarbase and Cytoscape and top 5 overexpressed miRNAs were selected, that will be analyzed in extracellular vesicles derived from ENZ resistance 3D spheroid models. We identified 12 up- and 13 downregulated miRNAs in LNCaP 30 μM ENZ cells compare to LNCaP·In silico analysis led to the construction of a 76 proteins cluster and functional enrichment revealed terms like PI3K/AKT, TFG-β and FOXO. hsa-miR-22-3p was significantly decreased at 5 and 20 μM ENZ concentration intracellularly, but significantly increased at 20 μM ENZ in EVs. hsa-miR-221-3p and miR-222-3p were upregulated in all concentrations both intracellularly and in EVs. The developed 3D-spheroid model effectively replicated the ENZ resistance to ENZ in an AR-independent manner, underscoring the importance of EVs-derived miRNAs in this adaptive process.
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Affiliation(s)
- Inês Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal
| | - Mariana Morais
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal
| | - Francisca Dias
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal
| | - Mariana Ferreira
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal
| | - Gabriela Martins
- Department of Immunology, Portuguese Oncology Institute of Porto (IPO- Porto), Porto, Portugal
| | - Rui Fernandes
- HEMS-Histology and Electron Microscopy, Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal; IBMC, Instituto de Biologia Molecular e Celular da Universidade do Porto, Porto, Portugal
| | - Sílvia Joana Bidarra
- Bioengineered 3D Microenvironment Group, Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal; INEB, Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal; ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Porto, Portugal; Biomedical Reasearch Center (CEBIMED), Faculty of Health Sciences, Fernando Pessoa University (UFP), Porto, Portugal; Research Department, Portuguese League Against Cancer (LPCC- NRNorte), Porto, Portugal; Faculty of Medicine, University of Porto (FMUP), University of Porto, Porto, Portugal
| | - Ana Luísa Teixeira
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal.
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Chen S, Lei Z, Sun T. The critical role of miRNA in bacterial zoonosis. Int Immunopharmacol 2024; 143:113267. [PMID: 39374566 DOI: 10.1016/j.intimp.2024.113267] [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: 05/06/2024] [Revised: 08/21/2024] [Accepted: 09/24/2024] [Indexed: 10/09/2024]
Abstract
The public's health and the financial sustainability of international societies remain threatened by bacterial zoonoses, with limited reliable diagnostic and therapeutic options available for bacterial diseases. Bacterial infections influence mammalian miRNA expression in host-pathogen interactions. In order to counteract bacterial infections, miRNAs participate in gene-specific expression and play important regulatory roles that rely on translational inhibition and target gene degradation by binding to the 3' non-coding region of target genes. Intriguingly, according to current studies, that exogenous miRNAs derived from plants could potentially serve as effective medicinal components sourced from traditional Chinese medicine plants. These exogenous miRNAs exhibit stable functionality in mammals and mimic the regulatory roles of endogenous miRNAs, illuminating the molecular processes behind the therapeutic effects of plants. This review details the immune defense mechanisms of inflammation, apoptosis, autophagy and cell cycle disturbance caused by some typical bacterial infections, summarizes the role of some mammalian miRNAs in regulating these mechanisms, and introduces the cGAS-STING signaling pathway in detail. Evidence suggests that this newly discovered immune defense mechanism in mammalian cells can also be affected by miRNAs. Meanwhile, some examples of transboundary regulation of mammalian mRNA and even bacterial diseases by exogenous miRNAs from plants are also summarized. This viewpoint provides fresh understanding of microbial tactics and host mechanisms in the management of bacterial illnesses.
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Affiliation(s)
- Si Chen
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China
| | - Zhixin Lei
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
| | - Taolei Sun
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
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Zou J, Xu B, Luo P, Chen T, Duan H. Non-coding RNAs in bladder cancer, a bridge between gut microbiota and host? Front Immunol 2024; 15:1482765. [PMID: 39628486 PMCID: PMC11611751 DOI: 10.3389/fimmu.2024.1482765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 10/30/2024] [Indexed: 12/06/2024] Open
Abstract
In recent years, the role of gut microbiota (GM) in bladder cancer has attracted significant attention. Research indicates that GM not only contributes to bladder carcinogenesis but also influences the efficacy of adjuvant therapies for bladder cancer. Despite this, interventions targeting GM have not been widely employed in the prevention and treatment of bladder cancer, mainly due to the incomplete understanding of the complex interactions between the host and gut flora. Simultaneously, aberrantly expressed non-coding RNAs (ncRNAs) have been frequently associated with bladder cancer, playing crucial roles in processes such as cell proliferation, invasion, and drug resistance. It is widely known that the regulation of GM-mediated host pathophysiological processes is partly regulated through epigenetic pathways. At the same time, ncRNAs are increasingly regarded as GM signaling molecules involved in GM-mediated epigenetic regulation. Accordingly, this review analyzes the ncRNAs that are closely related to the GM in the context of bladder cancer occurrence and treatment, and summarizes the role of their interaction with the GM in bladder cancer-related phenotypes. The aim is to delineate a regulatory network between GM and ncRNAs and provide a new perspective for the study and prevention of bladder cancer.
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Affiliation(s)
- Jun Zou
- Department of Otorhinolaryngology, The Affiliated Fengcheng Hospital of Yichun University, Fengcheng, Jiangxi, China
| | - Baisheng Xu
- Department of Urology, The First People's Hospital of Xiushui, Jiujiang, Jiangxi, China
| | - Peiyue Luo
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Tao Chen
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Huanglin Duan
- Department of Urology, The First People's Hospital of Xiushui, Jiujiang, Jiangxi, China
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Gozdz A, Maksym RB, Ścieżyńska A, Götte M, Kieda C, Włodarski PK, Malejczyk J. Expression of Reversion-Inducing Cysteine-Rich Protein with Kazal Motifs ( RECK) Gene and Its Regulation by miR200b in Ovarian Endometriosis. Int J Mol Sci 2024; 25:11594. [PMID: 39519143 PMCID: PMC11547164 DOI: 10.3390/ijms252111594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/22/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024] Open
Abstract
Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient's fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis.
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Affiliation(s)
- Agata Gozdz
- Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, ul. T. Chałubińskiego 5, 02-004 Warsaw, Poland; (R.B.M.); (A.Ś.); (P.K.W.)
| | - Radosław B. Maksym
- Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, ul. T. Chałubińskiego 5, 02-004 Warsaw, Poland; (R.B.M.); (A.Ś.); (P.K.W.)
- 1st Department of Obstetrics and Gynecology, Centre for Postgraduate Medical Education, ul. Żelazna 90, 01-004 Warsaw, Poland
- Center for Molecular Biophysics UPR 4301 CNRS, 45071 Orleans, France;
| | - Aneta Ścieżyńska
- Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, ul. T. Chałubińskiego 5, 02-004 Warsaw, Poland; (R.B.M.); (A.Ś.); (P.K.W.)
- Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, Poland
| | - Martin Götte
- Department of Obstetrics and Gynecology, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany;
- Cells-in-Motion Interfaculty Centre (CiMIC), University of Münster, 48149 Münster, Germany
| | - Claudine Kieda
- Center for Molecular Biophysics UPR 4301 CNRS, 45071 Orleans, France;
- Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, Poland
| | - Paweł K. Włodarski
- Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, ul. T. Chałubińskiego 5, 02-004 Warsaw, Poland; (R.B.M.); (A.Ś.); (P.K.W.)
| | - Jacek Malejczyk
- Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, ul. T. Chałubińskiego 5, 02-004 Warsaw, Poland; (R.B.M.); (A.Ś.); (P.K.W.)
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Ferreira M, Morais M, Medeiros R, Teixeira AL. MicroRNAs as Promising Therapeutic Agents Against Prostate Cancer Resistant to Castration-Where Are We Now? Pharmaceutics 2024; 16:1347. [PMID: 39598472 PMCID: PMC11597238 DOI: 10.3390/pharmaceutics16111347] [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: 09/02/2024] [Revised: 10/17/2024] [Accepted: 10/19/2024] [Indexed: 11/29/2024] Open
Abstract
MicroRNAs are a conserved class of small, tissue-specific, non-coding RNAs that regulate gene expression to preserve cellular homeostasis. Proper miRNA expression is crucial for physiological balance because it affects numerous genetic pathways, including cell cycle control, proliferation, and apoptosis, through gene expression targeting. Deregulated miRNA expression has been implicated in several cancer types, including prostate cancer (PC), acting as tumor suppressors or oncogenes. Despite the availability of promising therapies to control tumor growth and progression, effective diagnostic and therapeutic strategies for different types of cancer are still lacking. PC continues to be a significant health challenge, particularly its castration-resistant (CRPC) form, which presents major therapeutic obstacles because of its resistance to conventional androgen deprivation treatments. This review explores miRNAs' critical roles in gene regulation and cancer biology, as well as various miRNA delivery systems, highlighting their potential and the challenges in effectively targeting cancer cells. It aims to provide a comprehensive overview of the status of miRNA research in the fight against CRPC, summarizing miRNA-based therapies' successes and limitations. It also highlights the promise of miRNAs as therapeutic agents for CRPC, underlining the need for further research to overcome existing challenges and move these therapies toward clinical applications.
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Affiliation(s)
- Mariana Ferreira
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (M.F.); (M.M.); (R.M.)
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Mariana Morais
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (M.F.); (M.M.); (R.M.)
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (M.F.); (M.M.); (R.M.)
- ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
- Biomedical Research Center (CEBIMED), Faculty of Health Sciences, Fernando Pessoa University (UFP), 4249-004 Porto, Portugal
- Research Department, LPCC-Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal
- Faculty of Medicine (FMUP), University of Porto, 4200-319 Porto, Portugal
| | - Ana Luísa Teixeira
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (M.F.); (M.M.); (R.M.)
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9
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Leng X, Zhang M, Xu Y, Wang J, Ding N, Yu Y, Sun S, Dai W, Xue X, Li N, Yang Y, Shi Z. Non-coding RNAs as therapeutic targets in cancer and its clinical application. J Pharm Anal 2024; 14:100947. [PMID: 39149142 PMCID: PMC11325817 DOI: 10.1016/j.jpha.2024.02.001] [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: 10/27/2023] [Revised: 01/12/2024] [Accepted: 02/01/2024] [Indexed: 08/17/2024] Open
Abstract
Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression. Oncogenes promote cell growth and proliferation, whereas tumor suppressor genes inhibit cell growth and division. The dysregulation of these genes can lead to the development of cancer. Recent studies have focused on non-coding RNAs (ncRNAs), including circular RNA (circRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), as therapeutic targets for cancer. In this article, we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets. Here, we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment. Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.
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Affiliation(s)
- Xuejiao Leng
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Mengyuan Zhang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yujing Xu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jingjing Wang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ning Ding
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yancheng Yu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Shanliang Sun
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Weichen Dai
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Xin Xue
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Nianguang Li
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ye Yang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Zhihao Shi
- Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing, 211198, China
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10
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Aguilar-Martínez SY, Campos-Viguri GE, Medina-García SE, García-Flores RJ, Deas J, Gómez-Cerón C, Pedroza-Torres A, Bautista-Rodríguez E, Fernández-Tilapa G, Rodríguez-Dorantes M, Pérez-Plasencia C, Peralta-Zaragoza O. MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway. Int J Mol Sci 2024; 25:4086. [PMID: 38612895 PMCID: PMC11012906 DOI: 10.3390/ijms25074086] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 03/27/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3'-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.
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Affiliation(s)
- Seidy Y. Aguilar-Martínez
- Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico; (S.Y.A.-M.); (G.E.C.-V.); (S.E.M.-G.); (R.J.G.-F.); (J.D.)
| | - Gabriela E. Campos-Viguri
- Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico; (S.Y.A.-M.); (G.E.C.-V.); (S.E.M.-G.); (R.J.G.-F.); (J.D.)
| | - Selma E. Medina-García
- Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico; (S.Y.A.-M.); (G.E.C.-V.); (S.E.M.-G.); (R.J.G.-F.); (J.D.)
| | - Ricardo J. García-Flores
- Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico; (S.Y.A.-M.); (G.E.C.-V.); (S.E.M.-G.); (R.J.G.-F.); (J.D.)
| | - Jessica Deas
- Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico; (S.Y.A.-M.); (G.E.C.-V.); (S.E.M.-G.); (R.J.G.-F.); (J.D.)
| | - Claudia Gómez-Cerón
- Department of Epidemiology of Cancer, Research Center Population Health, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico;
| | - Abraham Pedroza-Torres
- Programa Investigadoras e Investigadores por México, Consejo Nacional de Humanidades, Ciencias y Tecnologías, México City 14080, Mexico;
- Hereditary Cancer Clinic, Instituto Nacional de Cancerología, México City 14080, Mexico
| | | | - Gloria Fernández-Tilapa
- Clinical Research Laboratory, Faculty of Chemical Biological Sciences, Universidad Autónoma de Guerrero, Chilpancingo 39070, Mexico;
| | | | - Carlos Pérez-Plasencia
- Oncogenomics Laboratory, Instituto Nacional de Cancerología, México City 14080, Mexico;
- Biomedicine Unit, FES-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz 54090, Mexico
| | - Oscar Peralta-Zaragoza
- Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico; (S.Y.A.-M.); (G.E.C.-V.); (S.E.M.-G.); (R.J.G.-F.); (J.D.)
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11
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Shi C, Yang D, Ma X, Pan L, Shao Y, Arya G, Ke Y, Zhang C, Wang F, Zuo X, Li M, Wang P. A Programmable DNAzyme for the Sensitive Detection of Nucleic Acids. Angew Chem Int Ed Engl 2024; 63:e202320179. [PMID: 38288561 DOI: 10.1002/anie.202320179] [Citation(s) in RCA: 29] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Indexed: 02/17/2024]
Abstract
Nucleic acids in biofluids are emerging biomarkers for the molecular diagnostics of diseases, but their clinical use has been hindered by the lack of sensitive detection assays. Herein, we report the development of a sensitive nucleic acid detection assay named SPOT (sensitive loop-initiated DNAzyme biosensor for nucleic acid detection) by rationally designing a catalytic DNAzyme of endonuclease capability into a unified one-stranded allosteric biosensor. SPOT is activated once a nucleic acid target of a specific sequence binds to its allosteric module to enable continuous cleavage of molecular reporters. SPOT provides a highly robust platform for sensitive, convenient and cost-effective detection of low-abundance nucleic acids. For clinical validation, we demonstrated that SPOT could detect serum miRNAs for the diagnostics of breast cancer, gastric cancer and prostate cancer. Furthermore, SPOT exhibits potent detection performance over SARS-CoV-2 RNA from clinical swabs with high sensitivity and specificity. Finally, SPOT is compatible with point-of-care testing modalities such as lateral flow assays. Hence, we envision that SPOT may serve as a robust assay for the sensitive detection of a variety of nucleic acid targets enabling molecular diagnostics in clinics.
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Affiliation(s)
- Chenzhi Shi
- Institute of Molecular Medicine, Department of Laboratory Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Center for DNA Information Storage, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Donglei Yang
- Institute of Molecular Medicine, Department of Laboratory Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Center for DNA Information Storage, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Xiaowei Ma
- Institute of Molecular Medicine, Department of Laboratory Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Center for DNA Information Storage, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Li Pan
- Institute of Molecular Medicine, Department of Laboratory Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Center for DNA Information Storage, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Yuanchuan Shao
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, 27708, USA
| | - Gaurav Arya
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina, 27708, USA
| | - Yonggang Ke
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, 30322, USA
| | - Chuan Zhang
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Fuan Wang
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei, 430072, China
| | - Xiaolei Zuo
- Institute of Molecular Medicine, Department of Laboratory Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Center for DNA Information Storage, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Min Li
- Institute of Molecular Medicine, Department of Laboratory Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Center for DNA Information Storage, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Pengfei Wang
- Institute of Molecular Medicine, Department of Laboratory Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Center for DNA Information Storage, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
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12
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Chawra HS, Agarwal M, Mishra A, Chandel SS, Singh RP, Dubey G, Kukreti N, Singh M. MicroRNA-21's role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology. Pathol Res Pract 2024; 254:155091. [PMID: 38194804 DOI: 10.1016/j.prp.2024.155091] [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: 12/02/2023] [Revised: 12/31/2023] [Accepted: 01/01/2024] [Indexed: 01/11/2024]
Abstract
MicroRNA-21 (miR-21) was recognized as a key figure in the intricate web of tumor biology, with a prominent role in regulating the PTEN tumor suppressor gene and the PI3K/AKT cascade. This review elucidates the multifaceted interactions between miR-21, PTEN, and the PI3K/AKT signaling, shedding light on their profound implications in cancer initiation, progression, and therapeutic strategies. The core of this review delves into the mechanical intricacies of miR-21-mediated PTEN suppression and its consequent impact on PI3K/AKT pathway activation. It explores how miR-21, as an oncogenic miRNA, targets PTEN directly or indirectly, resulting in uncontrolled activation of PI3K/AKT, fostering cancerous cell survival, proliferation, and evasion of apoptosis. Furthermore, the abstract emphasizes the clinical relevance of these molecular interactions, discussing their implications in various cancer types, prognostic significance, and potential as therapeutic targets. The review provides insights into ongoing research efforts to develop miR-21 inhibitors and strategies to restore PTEN function, offering new avenues for cancer treatment. This article illuminates the critical function of miR-21 in PTEN suppression and PI3K/AKT activation, offering profound insights into its implications for cancer biology and the potential for targeted interventions.
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Affiliation(s)
| | - Mohit Agarwal
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | - Anurag Mishra
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | | | | | - Gaurav Dubey
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | - Neelima Kukreti
- School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India
| | - Mithilesh Singh
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India.
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13
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Jacob TV, Doshi GM. A Mini-review on Helicobacter pylori with Gastric Cancer and Available Treatments. Endocr Metab Immune Disord Drug Targets 2024; 24:277-290. [PMID: 37622707 DOI: 10.2174/1871530323666230824161901] [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: 05/30/2023] [Revised: 07/22/2023] [Accepted: 07/26/2023] [Indexed: 08/26/2023]
Abstract
Helicobacter pylori (H. pylori) is the most thoroughly researched etiological component for stomach inflammation and malignancies. Even though there are conventional recommendations and treatment regimens for eradicating H. pylori, failure rates continue to climb. Antibiotic resistance contributes significantly to misdiagnoses, false positive results, and clinical failures, all of which raise the chance of infection recurrence. This review aims to explore the molecular mechanisms underlying drug resistance in H. pylori and discuss novel approaches for detecting genotypic resistance. Modulation of drug uptake/ efflux, biofilm, and coccoid development. Newer genome sequencing approaches capable of detecting H. pylori genotypic resistance are presented. Prolonged infection in the stomach causes major problems such as gastric cancer. The review discusses how H. pylori causes stomach cancer, recent biomarkers such as miRNAs, molecular pathways in the development of gastric cancer, and diagnostic methods and clinical trials for the disease. Efforts have been made to summarize the recent advancements made toward early diagnosis and novel therapeutic approaches for H. pylori-induced gastric cancer.
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Affiliation(s)
- Teresa V Jacob
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.M. Road, Vile Parle (W), Mumbai, 400056, India
| | - Gaurav M Doshi
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.M. Road, Vile Parle (W), Mumbai, 400056, India
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14
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Kalajahi HG, Yari A, Amini M, Catal T, Ahmadpour Youshanlui M, Pourbagherian O, Zhmurov CS, Mokhtarzadeh A. Therapeutic effect of microRNA-21 on differentially expressed hub genes in gastric cancer based on systems biology. Sci Rep 2023; 13:21906. [PMID: 38081950 PMCID: PMC10713559 DOI: 10.1038/s41598-023-49225-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 12/05/2023] [Indexed: 12/18/2023] Open
Abstract
Gastric cancer (GC) is a leading cause of mortality for many people. Cancer's initiating factors are poorly understood. miR-21 has a crucial function in several malignancies, particularly GC. Furthermore, it has been shown that miR-21 is critical for the emergence and advancement of GC. This work intends to identify new genes which expression is associated with the activity of mir-21 in GC and to investigate the effect of downregulation of mir-21 on these genes and gastric tumorigenesis. We utilized the gene expression profiles of GCs from an Array database (GSE13911) from the Gene Expression Omnibus (GEO) dataset to find differentially expressed genes (DEGs) between control and gastric cancer groups. Using weighted gene correlation network analysis (WGCNA) in R, the Gene co-expression network was reconstructed. The microRNA-mRNA network was then reconstructed using the miRWalk database, and by investigating the microRNA-mRNA network, the genes that have an association with mir-21 were found. To implement the functional investigation, MKN and AGS cell lines were transfected with anti-miR-21 next. Subsequently, MTT proliferation was utilized to assess the cell's vitality. qRT-PCR was then used to evaluate the anticipated levels of gene expression in both GC cell lines. This study discovered and predicted CCL28, NR3C2, and SNYPO2 as the targets of miR-21 (GC), which are downregulated through gastric tumorigenesis, showing great potential as therapeutic and diagnostic targets. The suppression of miR-21 in gastric GC cells led to the inhibition of cell proliferation and decreased expression of CCL28, NR3C2, and SNYPO2 genes. This study established that miR-21, via downregulating these genes, contributes significantly to the development of GC. In addition, systems biology techniques identified CCL28, NR3C2, and SNYPO2 genes as possible GC surveillance and therapy components.
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Affiliation(s)
- Hesam Ghafouri Kalajahi
- Department of Molecular Biology and Genetics, Uskudar University, Uskudar, 34662, Istanbul, Turkey
| | - AmirHossein Yari
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Tunc Catal
- Department of Molecular Biology and Genetics, Uskudar University, Uskudar, 34662, Istanbul, Turkey
| | | | - Omid Pourbagherian
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Cigdem Sezer Zhmurov
- Department of Molecular Biology and Genetics, Uskudar University, Uskudar, 34662, Istanbul, Turkey.
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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15
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Xie JB, Zhang H, Li XF, Han SY, Li XL. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway. Open Med (Wars) 2023; 18:20230776. [PMID: 38025524 PMCID: PMC10656762 DOI: 10.1515/med-2023-0776] [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: 03/21/2022] [Revised: 03/08/2023] [Accepted: 07/28/2023] [Indexed: 12/01/2023] Open
Abstract
This study aimed to investigate the interaction between miR-1278 and Caldesmon (CALD1) in gastric cancer (GC) and the regulatory mechanism. In both GC cells and tissues, the levels of CALD1, miR-1278, migration-related markers (E-cadherin, N-cadherin, and Snail), and MAPK signaling pathway-related proteins were clarified using quantitative real-time PCR and western blotting analyses. The effects of miR-1278 and CALD1 on GC cell viability and migration were analyzed using CCK-8 and Transwell assays, respectively. The targeting effect of miR-1278 on CALD1 was investigated using bioinformatics prediction and a dual luciferase reporter assay. The effect of miR-1278 on tumor growth was estimated in vivo using a tumor xenograft assay. In GC, miR-1278 expression decreased, whereas CALD1 was highly expressed. Transfecting an miR-1278 mimic into cells inhibited the viability as well as migration of GC cells, and suppressed Ras, phosphorylated (p)-P38, and p-ERK1/2 protein levels. Moreover, miR-1278 targeted and negatively regulated CALD1 expression. CALD1 overexpression promoted GC cell survival and migration and activated the MAPK pathway. Treatment with an miR-1278 mimic partially rescued the changes caused by CALD1 overexpression. Overall, our study revealed that miR-1278 suppresses the malignant behavior of GC cells by targeting CALD1 and regulating the MAPK pathway.
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Affiliation(s)
- Jia-Bei Xie
- Department of Gastroenterology and Hepatology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Jinshui District, Zhengzhou450003, Henan, China
| | - Hao Zhang
- Department of Gastroenterology and Hepatology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou450003, Henan, China
| | - Xiao-Fang Li
- Department of Gastroenterology and Hepatology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou450003, Henan, China
| | - Shuang-Yin Han
- Department of Gastroenterology and Hepatology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou450003, Henan, China
| | - Xiu-Ling Li
- Department of Gastroenterology and Hepatology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou450003, Henan, China
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16
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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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17
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Chakrabortty A, Patton DJ, Smith BF, Agarwal P. miRNAs: Potential as Biomarkers and Therapeutic Targets for Cancer. Genes (Basel) 2023; 14:1375. [PMID: 37510280 PMCID: PMC10378777 DOI: 10.3390/genes14071375] [Citation(s) in RCA: 79] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/25/2023] [Accepted: 06/25/2023] [Indexed: 07/30/2023] Open
Abstract
MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we comprehensively summarized the importance of miRNA in human and canine cancer research. We discussed the current state of development and potential for the miRNA as both a diagnostic marker and a therapeutic target.
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Affiliation(s)
- Atonu Chakrabortty
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
| | - Daniel J Patton
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
| | - Bruce F Smith
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
| | - Payal Agarwal
- Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
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18
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Lucarini V, Nardozi D, Angiolini V, Benvenuto M, Focaccetti C, Carrano R, Besharat ZM, Bei R, Masuelli L. Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion. Biomedicines 2023; 11:1761. [PMID: 37371856 DOI: 10.3390/biomedicines11061761] [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: 05/10/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
Gastrointestinal (GI) cancers are the most frequent neoplasm, responsible for half of all cancer-related deaths. Metastasis is the leading cause of death from GI cancer; thus, studying the processes that regulate cancer cell migration is of paramount importance for the development of new therapeutic strategies. In this review, we summarize the mechanisms adopted by cancer cells to promote cell migration and the subsequent metastasis formation by highlighting the key role that tumor microenvironment components play in deregulating cellular pathways involved in these processes. We, therefore, provide an overview of the role of different microRNAs in promoting tumor metastasis and their role as potential biomarkers for the prognosis, monitoring, and diagnosis of GI cancer patients. Finally, we relate the possible use of nutraceuticals as a new strategy for targeting numerous microRNAs and different pathways involved in GI tumor invasiveness.
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Affiliation(s)
- Valeria Lucarini
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Daniela Nardozi
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Valentina Angiolini
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Monica Benvenuto
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
- Departmental Faculty of Medicine and Surgery, Saint Camillus International University of Health and Medical Sciences, via di Sant'Alessandro 8, 00131 Rome, Italy
| | - Chiara Focaccetti
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Raffaele Carrano
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Zein Mersini Besharat
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Roberto Bei
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Laura Masuelli
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
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19
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Kashyap D, Rele S, Bagde PH, Saini V, Chatterjee D, Jain AK, Pandey RK, Jha HC. Comprehensive insight into altered host cell-signaling cascades upon Helicobacter pylori and Epstein-Barr virus infections in cancer. Arch Microbiol 2023; 205:262. [PMID: 37310490 DOI: 10.1007/s00203-023-03598-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/14/2023]
Abstract
Cancer is characterized by mutagenic events that lead to disrupted cell signaling and cellular functions. It is one of the leading causes of death worldwide. Literature suggests that pathogens, mainly Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with the etiology of human cancer. Notably, their co-infection may lead to gastric cancer. Pathogen-mediated DNA damage could be the first and crucial step in the carcinogenesis process that modulates numerous cellular signaling pathways. Altogether, it dysregulates the metabolic pathways linked with cell growth, apoptosis, and DNA repair. Modulation in these pathways leads to abnormal growth and proliferation. Several signaling pathways such RTK, RAS/MAPK, PI3K/Akt, NFκB, JAK/STAT, HIF1α, and Wnt/β-catenin are known to be altered in cancer. Therefore, this review focuses on the oncogenic roles of H. pylori, EBV, and its associated signaling cascades in various cancers. Scrutinizing these signaling pathways is crucial and may provide new insights and targets for preventing and treating H. pylori and EBV-associated cancers.
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Affiliation(s)
- Dharmendra Kashyap
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | - Samiksha Rele
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | - Pranit Hemant Bagde
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | - Vaishali Saini
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | | | | | - Rajan Kumar Pandey
- Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177, Solna, Sweden
| | - Hem Chandra Jha
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India.
- Centre for Rural Development and Technology, Indian Institute of Technology Indore, Madhya Pradesh, 453552, Indore, India.
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20
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Fathi D, Elballal MS, Elesawy AE, Abulsoud AI, Elshafei A, Elsakka EG, Ismail A, El-Mahdy HA, Elrebehy MA, Doghish AS. An emphasis on the interaction of signaling pathways highlights the role of miRNAs in the etiology and treatment resistance of gastric cancer. Life Sci 2023; 322:121667. [PMID: 37023952 DOI: 10.1016/j.lfs.2023.121667] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 04/01/2023] [Accepted: 04/03/2023] [Indexed: 04/07/2023]
Abstract
Gastric cancer (GC) is 4th in incidence and mortality rates globally. Several genetic and epigenetic factors, including microRNAs (miRNAs), affect its initiation and progression. miRNAs are short chains of nucleic acids that can regulate several cellular processes by controlling their gene expression. So, dysregulation of miRNAs expressions is associated with GC initiation, progression, invasion capacity, apoptosis evasions, angiogenesis, promotion and EMT enhancement. Of important pathways in GC and controlled by miRNAs are Wnt/β-catenin signaling, HMGA2/mTOR/P-gp, PI3K/AKT/c-Myc, VEGFR and TGFb signaling. Hence, this review was conducted to review an updated view of the role of miRNAs in GC pathogenesis and their modulatory effects on responses to different GC treatment modalities.
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21
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Yang H, Liao C, Zhang Z, Zhan P, Chen YR. Wheel drive-based DNA sensing system for highly specific and rapid one-step detection of MiRNAs at the attomolar level. Talanta 2023; 257:124371. [PMID: 36841015 DOI: 10.1016/j.talanta.2023.124371] [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: 08/22/2022] [Revised: 12/06/2022] [Accepted: 02/14/2023] [Indexed: 02/19/2023]
Abstract
With the use of DNA as building blocks, a variety of microRNA amplification-based sensing systems have been developed. Nevertheless, ultrasensitive, selective and rapid detection of microRNAs with a high signal-to-background ratio and point mutation discrimination ability remains a challenge. Herein, we propose a novel wheel drive-based DNA sensing system (NWDS) based on a self-assembled, self-quenched nanoprobe (SQP) to conduct highly specific and ultrasensitive one-step measurement of microRNAs. In this work, a signalling recognition DNA hairpin (DH) sequence with a self-complementary stem domain of 14 base pairs was used, which contained three functional regions, namely a recognition region for the target miRNA-21, a sticky region with 9 complementary nucleotides to the 3'terminus of a DNA wheel (DW) and a region for the hybridization with a quenching DNA primer (DP). The SQP was ingeniously self-assembled at room temperature by the DH and DP, which was capable of eliminating unwanted background signals. MiRNA-21 was employed as a target model to specifically activate the SQP, leading to specific hybridization between the HP and DW. With the assistance of a polymerase, an SQP-based wheel driving took place to induce hybridization/polymerization displacement cycles, initiating target recycling and DP displacement. As a result, a large amount of the newly formed hybrid SQP/DW accumulated to generate a substantially enhanced fluorescence signal. In this way, the newly proposed NWDS exhibits ultrasensitivity with a detection limit of 5.62 aM across a wide linear dynamic response range up to 200 nM, excellent selectivity with the capability to discriminate homologous miRNAs and one-base, two-base and three-base mismatched sequences, and an outstanding analytical performance in complex systems. In addition, the significant simultaneous advantages of one-step operation, rapid detection within 15 min and a high signal-to-background ratio of 26 offer a unique opportunity to promote the early diagnosis of cancer-related diseases and molecular biological analysis.
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Affiliation(s)
- Hongbao Yang
- Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Chuanwen Liao
- Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Zhen Zhang
- Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Ping Zhan
- Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China; Dermatology Department, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, China.
| | - Yan-Ru Chen
- Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China.
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22
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Pani G. Fusobacterium & Co. at the Stem of Cancer: Microbe-Cancer Stem Cell Interactions in Colorectal Carcinogenesis. Cancers (Basel) 2023; 15:cancers15092583. [PMID: 37174049 PMCID: PMC10177588 DOI: 10.3390/cancers15092583] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 04/27/2023] [Accepted: 04/27/2023] [Indexed: 05/15/2023] Open
Abstract
Adult stem cells lie at the crossroads of tissue repair, inflammation, and malignancy. Intestinal microbiota and microbe-host interactions are pivotal to maintaining gut homeostasis and response to injury, and participate in colorectal carcinogenesis. Yet, limited knowledge is available on whether and how bacteria directly crosstalk with intestinal stem cells (ISC), particularly cancerous stem-like cells (CR-CSC), as engines for colorectal cancer initiation, maintenance, and metastatic dissemination. Among several bacterial species alleged to initiate or promote colorectal cancer (CRC), the pathobiont Fusobacterium Nucleatum has recently drawn significant attention for its epidemiologic association and mechanistic linkage with the disease. We will therefore focus on current evidence for an F. nucleatum-CRCSC axis in tumor development, highlighting the commonalities and differences between F. nucleatum-associated colorectal carcinogenesis and gastric cancer driven by Helicobacter Pylori. We will explore the diverse facets of the bacteria-CSC interaction, analyzing the signals and pathways whereby bacteria either confer "stemness" properties to tumor cells or primarily target stem-like elements within the heterogeneous tumor cell populations. We will also discuss the extent to which CR-CSC cells are competent for innate immune responses and participate in establishing a tumor-promoting microenvironment. Finally, by capitalizing on the expanding knowledge of how the microbiota and ISC crosstalk in intestinal homeostasis and response to injury, we will speculate on the possibility that CRC arises as an aberrant repair response promoted by pathogenic bacteria upon direct stimulation of intestinal stem cells.
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Affiliation(s)
- Giovambattista Pani
- Department of Translational Medicine and Surgery, Section of General Pathology, Faculty of Medicine, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168 Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, L. go A. Gemelli 8, 00168 Rome, Italy
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23
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Cao X, Dong J, Sun R, Zhang X, Chen C, Zhu Q. A DNAzyme-enhanced nonlinear hybridization chain reaction for sensitive detection of microRNA. J Biol Chem 2023; 299:104751. [PMID: 37100287 DOI: 10.1016/j.jbc.2023.104751] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/17/2023] [Accepted: 04/20/2023] [Indexed: 04/28/2023] Open
Abstract
As a typical biomarker, the expression of microRNA is closely related to the occurrence of cancer. However, in recent years, the detection methods have had some limitations in the research and application of microRNAs. In this paper, an autocatalytic platform was constructed through the combination of a nonlinear hybridization chain reaction and DNAzyme to achieve efficient detection of microRNA-21. Fluorescently labeled fuel probes can form branched nanostructures and new DNAzyme under the action of the target, and the newly formed DNAzyme can trigger a new round of reactions, resulting in enhanced fluorescence signals. This platform is a simple, efficient, fast, low-cost, and selective method for the detection of microRNA-21, which can detect microRNA-21 at concentrations as low as 0.004 nM and can distinguish sequence differences by single-base differences. In tissue samples from liver cancer patients, the platform shows the same detection accuracy as real-time PCR but with better reproducibility. In addition, through the flexible design of the trigger chain, our method could be adapted to detect other nucleic acids biomarkers.
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Affiliation(s)
- Xiuen Cao
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China
| | - Jiani Dong
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China
| | - Ruowei Sun
- Hunan Zaochen Nanorobot Co. Ltd, Liuyang 410300, Hunan, China
| | - Xun Zhang
- Hunan Zaochen Nanorobot Co. Ltd, Liuyang 410300, Hunan, China
| | - Chuanpin Chen
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China.
| | - Qubo Zhu
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China.
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24
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Xia R, Chai H, Jiao J, Miao P. Assembly of DNA triangular pyramid frustum for ultrasensitive quantification of exosomal miRNA. Biosens Bioelectron 2023; 231:115297. [PMID: 37031505 DOI: 10.1016/j.bios.2023.115297] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/14/2023] [Accepted: 04/03/2023] [Indexed: 04/11/2023]
Abstract
Early screening of biomarkers benefits therapy and prognosis of cancers. MiRNAs encapsulated in tumor-derived exosomes are emerging biomarkers for early diagnosis of cancers. Nevertheless, traditional methods suffer certain drawbacks, which hamper their wide applications. In this contribution, we have developed a convenient electrochemical approach for quantification of exosomal miRNA based on the assembly of DNA triangular pyramid frustum (TPF) and strand displacement amplification. Four single-stranded DNA helps the formation of primary DNA triangle with three thiols for gold electrode immobilization at the bottom and three amino groups on overhangs for the capture of silver nanoparticles. On the other hand, target miRNA induced strand displacement reaction produces abundant specific DNA strands, which help the DNA structural transition from triangle to TPF. Amino groups are thus hidden and the declined silver stripping current can be used for the evaluation of target miRNA concentration. This biosensor exhibits excellent analytical performances and successfully achieves analysis of exosomal miRNAs from cells and clinical serum samples.
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Affiliation(s)
- Renpeng Xia
- University of Science and Technology of China, Hefei, 230026, PR China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, PR China
| | - Hua Chai
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, PR China
| | - Jin Jiao
- School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, PR China.
| | - Peng Miao
- University of Science and Technology of China, Hefei, 230026, PR China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, PR China.
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25
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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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26
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Tong T, Zhou Y, Huang Q, Xiao C, Bai Q, Deng B, Chen L. The regulation roles of miRNAs in Helicobacter pylori infection. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023:10.1007/s12094-023-03094-9. [PMID: 36781601 DOI: 10.1007/s12094-023-03094-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 01/17/2023] [Indexed: 02/15/2023]
Abstract
Helicobacter pylori is a kind of Gram-negative bacteria that parasitizes on human gastric mucosa. Helicobacter pylori infection is very common in human beings, which often causes gastrointestinal diseases, including chronic gastritis, duodenal ulcer and gastric cancer. MicroRNAs are a group of endogenous non-coding single stranded RNAs, which play an important role in cell proliferation, differentiation, autophagy, apoptosis and inflammation. In recent years, relevant studies have found that the expression of microRNA is changed after Helicobacter pylori infection, and then regulate the biological process of host cells. This paper reviews the regulation role of microRNAs on cell biological behavior through different signal pathways after Helicobacter pylori infection.
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Affiliation(s)
- Ting Tong
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - You Zhou
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Qiaoling Huang
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Cui Xiao
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Qinqin Bai
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Bo Deng
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Lili Chen
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. .,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. .,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China.
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27
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Allahverdy J, Rashidi N. MicroRNAs induced by Listeria monocytogenes and their role in cells. Microb Pathog 2023; 175:105997. [PMID: 36669673 DOI: 10.1016/j.micpath.2023.105997] [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: 07/26/2022] [Revised: 01/16/2023] [Accepted: 01/16/2023] [Indexed: 01/19/2023]
Abstract
Listeria monocytogenes (Lm) causes abortions at high rates and threatens newborns' lives. Also, the elderly and immunocompromised individuals are particularly vulnerable neurologically. The bacterium exerts its pathogenesis intracellularly by manipulating cell organs. It manipulates nucleus elements, microRNAs (miRNAs), in order to increase survival and evade immunity. miRNAs are small non-coding RNAs that degrade gene expression post-transcriptionally. Any alteration to the expression of miRNAs affects various cascades in cells, especially immunity-related responses. Thus, utilizing miRNAs as a novel therapeutic agent not only restricts infection but enhances immunity reactions. This review provides an overview of miRNAs in listeriosis, their role in cells, and their prospects as therapy.
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Affiliation(s)
- Javad Allahverdy
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Niloufar Rashidi
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
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28
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Lepcha TT, Kumar M, Sharma AK, Mal S, Majumder D, Jana K, Basu J, Kundu M. Uncovering the role of microRNA671-5p/CDCA7L/monoamine oxidase-A signaling in Helicobacter pylori mediated apoptosis in gastric epithelial cells. Pathog Dis 2023; 81:7143101. [PMID: 37140023 DOI: 10.1093/femspd/ftad006] [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: 02/09/2023] [Revised: 03/27/2023] [Accepted: 04/24/2023] [Indexed: 05/05/2023] Open
Abstract
Helicobacter pylori is a gram-negative microaerophilic bacterium and is associated with gastrointestinal diseases ranging from peptic ulcer and gastritis to gastric cancer and mucosa-associated lymphoid tissue lymphoma. In our laboratory, the transcriptomes and miRnomes of AGS cells infected with H. pylori have been profiled, and an miRNA-mRNA network has been constructed. MicroRNA 671-5p is upregulated during H. pylori infection of AGS cells or of mice. In this study, the role of miR-671-5p during infection has been investigated. It has been validated that miR-671-5p targets the transcriptional repressor CDCA7L, which is downregulated during infection (in vitro and in vivo) concomitant with miR-671-5p upregulation. Further, it has been established that the expression of monoamine oxidase A (MAO-A) is repressed by CDCA7L, and that MAO-A triggers the generation of reactive oxygen species (ROS). Consequently, miR-671-5p/CDCA7L signaling is linked to the generation of ROS during H. pylori infection. Finally, it has been demonstrated that ROS-mediated caspase 3 activation and apoptosis that occurs during H. pylori infection, is dependent on the miR-671-5p/CDCA7L/MAO-A axis. Based on the above reports, it is suggested that targeting miR-671-5p could offer a means of regulating the course and consequences of H. pylori infection.
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Affiliation(s)
- Thurbu Tshering Lepcha
- Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road Kolkata 700009, India
| | - Manish Kumar
- Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road Kolkata 700009, India
| | - Arun Kumar Sharma
- Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road Kolkata 700009, India
| | - Soumya Mal
- Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road Kolkata 700009, India
| | - Debayan Majumder
- Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road Kolkata 700009, India
| | - Kuladip Jana
- Division of Molecular Medicine, Bose Institute, EN80 Sector V, Salt Lake City, Kolkata 700091, India
| | - Joyoti Basu
- Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road Kolkata 700009, India
| | - Manikuntala Kundu
- Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road Kolkata 700009, India
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29
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Dhuri K, Pradeep SP, Shi J, Anastasiadou E, Slack FJ, Gupta A, Zhong XB, Bahal R. Simultaneous Targeting of Multiple oncomiRs with Phosphorothioate or PNA-Based Anti-miRs in Lymphoma Cell Lines. Pharm Res 2022; 39:2709-2720. [PMID: 36071352 PMCID: PMC9879158 DOI: 10.1007/s11095-022-03383-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 08/27/2022] [Indexed: 01/29/2023]
Abstract
PURPOSE MicroRNAs (miRNAs) are short (~ 22 nts) RNAs that regulate gene expression via binding to mRNA. MiRNAs promoting cancer are known as oncomiRs. Targeting oncomiRs is an emerging area of cancer therapy. OncomiR-21 and oncomiR-155 are highly upregulated in lymphoma cells, which are dependent on these oncomiRs for survival. Targeting specific miRNAs and determining their effect on cancer cell progression and metastasis have been the focus of various studies. Inhibiting a single miRNA can have a limited effect, as there may be other overexpressed miRNAs present that may promote tumor proliferation. Herein, we target miR-21 and miR-155 simultaneously using nanoparticles delivered two different classes of antimiRs: phosphorothioates (PS) and peptide nucleic acids (PNAs) and compared their efficacy in lymphoma cell lines. METHODS Poly-Lactic-co-Glycolic acid (PLGA) nanoparticles (NPs) containing PS and PNA-based antimiR-21 and -155 were formulated, and comprehensive NP characterizations: morphology (scanning electron microscopy), size (differential light scattering), and surface charge (zeta potential) were performed. Cellular uptake analysis was performed using a confocal microscope and flow cytometry analysis. The oncomiR knockdown and the effect on downstream targets were confirmed by gene expression (real time-polymerase chain reaction) assay. RESULTS We demonstrated that simultaneous targeting with NP delivered PS and PNA-based antimiRs resulted in significant knockdown of miR-21 and miR-155, as well as their downstream target genes followed by reduced cell viability ex vivo. CONCLUSIONS This project demonstrated that targeting miRNA-155 and miR-21 simultaneously using nanotechnology and a diverse class of antisense oligomers can be used as an effective approach for lymphoma therapy.
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Affiliation(s)
- Karishma Dhuri
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Sai Pallavi Pradeep
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Jason Shi
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Eleni Anastasiadou
- HMS Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA
| | - Frank J Slack
- HMS Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA
| | - Anisha Gupta
- School of Pharmacy, University of Saint Joseph, West Hartford, CT, 06117, USA
| | - Xiao-Bo Zhong
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA
| | - Raman Bahal
- Department of Pharmaceutical Science, University of Connecticut, Storrs, CT, 06269, USA.
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Banerjee S, Mandal AKA. Role of epigallocatechin-3- gallate in the regulation of known and novel microRNAs in breast carcinoma cells. Front Genet 2022; 13:995046. [PMID: 36276982 PMCID: PMC9582282 DOI: 10.3389/fgene.2022.995046] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/15/2022] [Indexed: 11/24/2022] Open
Abstract
Breast cancer comprises 30% of all cancer cases among the world’s women population. MicroRNAs are small, endogenous, non-coding RNAs that regulate cell proliferating and apoptotic pathways by modulating expressions of related genes. Phytochemicals like epigallocatechin-3-gallate (EGCG) are known to have a chemotherapeutic effect on cancer often through the regulation of microRNAs. The aim is to find out the key known and novel miRNAs, which are controlled by EGCG in breast cancer cell line MDA-MB-231. Next-generation sequencing (NGS) revealed 1,258 known and 330 novel miRNAs from untreated and 83 μM EGCG (IC50 value of EGCG) treated cells. EGCG modulated 873 known and 47 novel miRNAs in the control vs. treated sample. The hypothesis of EGCG being a great modulator of miRNAs that significantly control important cancer-causing pathways has been established by analyzing with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Analysis Through Evolutionary Relationships (PANTHER) database. Validation of known and novel miRNA expression differences in untreated vs. treated cells was done using qPCR. From this study, a few notable miRNAs were distinguished that can be used as diagnostics as well as prognostic markers for breast cancer.
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Akhtarkhavari T, Bahrami AR, M Matin M. Downregulation of miR-21 as a promising strategy to overcome drug resistance in cancer. Eur J Pharmacol 2022; 932:175233. [PMID: 36038011 DOI: 10.1016/j.ejphar.2022.175233] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 08/09/2022] [Accepted: 08/22/2022] [Indexed: 11/30/2022]
Abstract
Despite tremendous achievements in the field of targeted cancer therapy, chemotherapy is still the main treatment option, which is challenged by acquired drug resistance. Various microRNAs are involved in developing drug-resistant cells. miR-21 is one of the first identified miRNAs involved in this process. Here, we conducted a literature review to categorize different mechanisms employed by miR-21 to drive drug resistance. miR-21 targets various genes involved in many pathways that can justify chemoresistance. It alters cancer cell metabolism and facilitates adaptation to the new environment. It also enhances drug detoxification in cancerous cells and increases genomic instability. We also summarized various strategies applied for the inhibition of miR-21 in order to reverse cancer drug resistance. These strategies include the delivery of antagomiRs, miRZip knockdown vectors, inhibitory small molecules, CRISPR-Cas9 technology, catalytic nucleic acids, artificial DNA and RNA sponges, and nanostructures like mesoporous silica nanoparticles, dendrimers, and exosomes. Furthermore, current challenges and limitations in targeting miR-21 are discussed in this article. Although huge progress has been made in the downregulation of miR-21 in drug-resistant cancer cells, there are still many challenges to be resolved. More research is still required to find the best strategy and timeline for the downregulation of miR-21 and also the most feasible approach for the delivery of this system into the tumor cells. In conclusion, downregulation of miR-21 would be a promising strategy to reverse chemoresistance, but still, more studies are required to clarify the aforementioned issues.
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Affiliation(s)
- Tara Akhtarkhavari
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Ahmad Reza Bahrami
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Maryam M Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran; Stem Cell and Regenerative Medicine Research Group, Academic Center for Education, Culture and Research (ACECR)-Khorasan Razavi, Mashhad, Iran.
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Meng X, Pang X, Zhang K, Gong C, Yang J, Dong H, Zhang X. Recent Advances in Near-Infrared-II Fluorescence Imaging for Deep-Tissue Molecular Analysis and Cancer Diagnosis. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2202035. [PMID: 35762403 DOI: 10.1002/smll.202202035] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/23/2022] [Indexed: 06/15/2023]
Abstract
Fluorescence imaging with high sensitivity and minimal invasiveness has received tremendous attention, which can accomplish visualized monitoring and evaluation of cancer progression. Compared with the conventional first near-infrared (NIR-I) optical window (650-950 nm), fluorescence imaging in the second NIR optical window (NIR-II, 950-1700 nm) exhibits deeper tissue penetration capability and higher temporal-spatial resolution with lower background interference for achieving deep-tissue in vivo imaging and real-time monitoring of cancer development. Encouraged by the significant preponderances, a variety of multifunctional NIR-II fluorophores have been designed and fabricated for sensitively imaging biomarkers in vivo and visualizing the treatment procedure of cancers. In this review, the differences between NIR-I and NIR-II fluorescence imaging are briefly introduced, especially the advantages of NIR-II fluorescence imaging for the real-time visualization of tumors in vivo and cancer diagnosis. An important focus is to summarize the NIR-II fluorescence imaging for deep-tissue biomarker analysis in vivo and tumor tissue visualization, and a brief introduction of NIR-II fluorescence imaging-guided cancer therapy is also presented. Finally, the significant challenges and reasonable prospects of NIR-II fluorescence imaging for cancer diagnosis in clinical applications are outlined.
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Affiliation(s)
- Xiangdan Meng
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Centre for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
| | - Xuejiao Pang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Centre for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
| | - Kai Zhang
- College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Chenchen Gong
- School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, P. R. China
| | - Junyan Yang
- School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, P. R. China
| | - Haifeng Dong
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Centre for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
- Marshall Laboratory of Biomedical Engineering, School of Biomedical Engineering, Health Science Centre, Shenzhen University, Shenzhen, 518071, P. R. China
| | - Xueji Zhang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Centre for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
- Marshall Laboratory of Biomedical Engineering, School of Biomedical Engineering, Health Science Centre, Shenzhen University, Shenzhen, 518071, P. R. China
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Zingone F, Pilotto V, Cardin R, Maddalo G, Orlando C, Fassan M, Marsilio I, Collesei E, Pelizzaro F, Farinati F. Autoimmune Atrophic Gastritis: The Role of miRNA in Relation to Helicobacter Pylori Infection. Front Immunol 2022; 13:930989. [PMID: 35941891 PMCID: PMC9356369 DOI: 10.3389/fimmu.2022.930989] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/23/2022] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION MicroRNAs (miRNAs) have been proposed as diagnostic markers, biomarkers of neoplastic progression, and possible therapeutic targets in several immune-mediated diseases. We aimed to analyze the expression profile of selected miRNAs (miR21, miR142, miR223, miR155) in patients with autoimmune atrophic gastritis (AAG), patients with non-autoimmune multifocal atrophic gastritis (MAG), and healthy control subjects (HC). MATERIALS AND METHODS A total of 103 patients with AAG were consecutively recruited for this study among those attending our gastroenterology outpatient clinic. Participating patients were divided into two groups: primary, not Helicobacter pylori (HP)-associated related AAG (n=57, P-AAG) and HP-associated AAG (n=46, HP-AAG); this subgroup included HP-positive patients, patients with previously reported HP infection, and patients harboring antral atrophy, considered as a stigma of HP infection. We also included 20 sex-age-matched MAG patients and 10 HC. Upper endoscopy with gastric biopsies were performed on each AAG and MAG patient. Circulating levels of miR21-5p, miR142-3p, miR223-3p, and miR155-5p were measured by RT-PCR in all groups. RESULTS MiR-21 was over-expressed in P-AAG (p=0.02), HP-AAG (p = 0.04), and MAG (p=0.03) compared with HC. By contrast, miR-142 was more expressed in HC than in HP-AAG (p=0.04) and MAG (p=0.03). MiR-155 showed no significant differences among the four subgroups, while, unexpectedly, miR-223 was overexpressed in HC compared to P-AAG (p=0.01), HP-AAG (p=0.003), and MAG (p<0.001), and was higher in P-AAG than in MAG (p=0.05). CONCLUSIONS MiR-21 was over-expressed in patients with gastric precancerous conditions irrespective of etiology, while in the same subgroups miR-142 and miR-223 were under-expressed compared to healthy controls. Controlling miRNAs up- or downregulation could lead to a breakthrough in treating chronic autoimmune diseases and potentially interfere with the progression to cancer.
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Affiliation(s)
- Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Valentina Pilotto
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Romilda Cardin
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Gemma Maddalo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Costanza Orlando
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Matteo Fassan
- Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy
- Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy
| | - Ilaria Marsilio
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Eugenio Collesei
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
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Wang YC, Lu S, Zhou XJ, Yang L, Liu P, Zhang L, Hu Y, Dong XZ. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis. Open Med (Wars) 2022; 17:930-946. [PMID: 35647303 PMCID: PMC9113083 DOI: 10.1515/med-2022-0486] [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: 10/17/2021] [Revised: 04/15/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to verify the biological function of miR-1273h-5p in gastric cancer (GC) and its underlying mechanisms. The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected using microarrays, miR-1273h-5p, and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA, and protein levels were evaluated using polymerase chain reaction and Western blotting methods, cell proliferation, apoptosis, migration, and invasion were determined by CCK-8, flow cytometry, and transwell assay. Compared to tumor-adjacent normal tissue and gastric epithelial mucosa cell line cells, miR-1273h-5p was significantly downregulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant upregulation of CXCL12 was observed when the miR-1273h-5p was downregulated in GC cells. Additionally, miR-1273h-5p significantly reduces tumor volume and weight. Thus, this study suggests that miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3′-untranslational regions, which may be a novel diagnostic and therapeutic target in GC.
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Affiliation(s)
- Yi-Chen Wang
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Song Lu
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.,College of Pharmacy, Zunyi Medical University, Zunyi 563000, China
| | - Xiao-Jiang Zhou
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Li Yang
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.,College of Pharmacy, Zunyi Medical University, Zunyi 563000, China
| | - Ping Liu
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Lan Zhang
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
| | - Yuan Hu
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, No. 28 FuXing Road, Haidian District, Beijing 100853, China
| | - Xian-Zhe Dong
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, 45 Changchun Road, Xicheng District, Beijing 100053, China
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Lidocaine Suppresses Gastric Cancer Development Through Circ_ANO5/miR-21-5p/LIFR Axis. Dig Dis Sci 2022; 67:2244-2256. [PMID: 34050852 DOI: 10.1007/s10620-021-07055-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/11/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND Lidocaine has been manifested to exert anti-tumor role in gastric cancer (GC) progression. However, the action mechanism by which Lidocaine functions in GC has not been fully elucidated. AIM The study aimed to reveal the molecular mechanism of Lidocaine in GC progression. METHODS Cell clonogenicity and viability were assessed by colony formation and methyl thiazolyl tetrazolium assays, respectively. Transwell assay was employed to detect cell migration and invasion. Flow cytometry was implemented to monitor cell apoptosis. Relative expression of circular RNA ANO5 (circ_ANO5), microRNA (miR)-21-5p and Leukemia inhibitory factor receptor (LIFR) was examined by quantitative reverse transcription-polymerase chain reaction. Western blot assay was performed to analyze the levels of LIFR and cell metastasis-related proteins. The target relationship between miR-21-5p and circ_ANO5 or LIFR was confirmed by dual-luciferase reporter assay. In addition, xenograft model was established to explore the role of Lidocaine in vivo. RESULTS Lidocaine inhibited cell proliferation, migration and invasion, while promoted apoptosis of GC cells. Lidocaine upregulated circ_ANO5 and LIFR expression, but downregulated miR-21-5p expression in GC cells. Additionally, expression of circ_ANO5 and LIFR was decreased, while miR-21-5p expression was increased in GC cells. Circ_ANO5 depletion or miR-21-5p overexpression attenuated Lidocaine-induced anti-proliferative and anti-metastatic effects on GC cells. Circ_ANO5 could sponge miR-21-5p, and miR-21-5p targeted LIFR. Moreover, Lidocaine suppressed the tumor growth in vivo. CONCLUSION Lidocaine might GC cell malignancy by modulating circ_ANO5/miR-21-5p/LIFR axis, highlighting a novel insight for GC treatment.
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Qiu L, Weng G. The diagnostic value of serum miR-21 in patients with ovarian cancer: a systematic review and meta-analysis. J Ovarian Res 2022; 15:51. [PMID: 35501921 PMCID: PMC9059364 DOI: 10.1186/s13048-022-00985-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 04/19/2022] [Indexed: 11/20/2022] Open
Abstract
Objective There have been a variety of published studies on the expression of serum miR-21 in patients with ovarian cancer associated with the diagnostic value of ovarian cancer, but the conclusions are not clearly elucidated. This study aims to evaluate the value of serum miR-21 expression in the diagnosis of patients with ovarian cancer by meta-analysis. Methods Databases, such as PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China WanFang, were searched for relevant studies upon the correlation between the expression of serum miR-21 and the diagnostic value of ovarian cancer from inception to March 7, 2022. Statistical analysis was performed using Stata 15.0 software. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. The meta-regression analysis and subgroup analysis were used to explore the sources of heterogeneity. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) system was used to evaluate the quality of the included literature. Results A total of 6 articles were included in the meta-analysis. The results showed that the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.81 (95%CI: 0.73–0.88), 0.82 (95%CI: 0.75–0.87), 4.51 (95%CI: 3.22–6.31), 0.23 (95%CI: 0.16–0.33), and 19.87 (95% CI: 11.27–35.03), respectively. The area under the summary receiver operating characteristic curve was 0.89 (95%CI: 0.85–0.91). No significant publication bias was found (P > 0.05). Conclusion Serum miR-21 has a good diagnostic value for ovarian cancer, which can be an ideal diagnostic biomarker for ovarian cancer. However, we should gingerly use miR-21 as a diagnostic reference standard, due to the limited number of included studies and heterogeneity.
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The PI3K/AKT signaling pathway in cancer: Molecular mechanisms and possible therapeutic interventions. Exp Mol Pathol 2022; 127:104787. [DOI: 10.1016/j.yexmp.2022.104787] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 04/15/2022] [Accepted: 05/21/2022] [Indexed: 01/02/2023]
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Rihane FE, Erguibi D, Lamsisi M, Chehab F, Ennaji MM. RETRACTED ARTICLE: Upregulation of miR-21 Expression in Gastric Cancer and Its Clinicopathological Feature Association. J Gastrointest Cancer 2022; 53:236. [PMID: 34907506 DOI: 10.1007/s12029-021-00691-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2021] [Indexed: 12/29/2022]
Affiliation(s)
- Fatima Ezzahra Rihane
- Laboratory of Genetic and Molecular Pathology, Faculty of Medicine & Pharmacy Casablanca, University Hassan II of Casablanca, Casablanca, Morocco
- Laboratory of Virology, Microbiology, Quality, Biotechnologies/Ecotoxicology and Biodiversity, Faculty of Sciences & Technologies Mohammedia, University Hassan II of Casablanca, Casablanca, Morocco
| | - Driss Erguibi
- Service of Digestive Cancers Surgery and Liver Transplant, Department of Surgery, Ibn Rochd University Hospital Center, Faculty of Medicine & Pharmacy Casablanca, University Hassan II of Casablanca, Casablanca, Morocco
| | - Maryame Lamsisi
- Laboratory of Virology, Microbiology, Quality, Biotechnologies/Ecotoxicology and Biodiversity, Faculty of Sciences & Technologies Mohammedia, University Hassan II of Casablanca, Casablanca, Morocco
| | - Farid Chehab
- Service of Digestive Cancers Surgery and Liver Transplant, Department of Surgery, Ibn Rochd University Hospital Center, Faculty of Medicine & Pharmacy Casablanca, University Hassan II of Casablanca, Casablanca, Morocco
| | - Moulay Mustapha Ennaji
- Laboratory of Virology, Microbiology, Quality, Biotechnologies/Ecotoxicology and Biodiversity, Faculty of Sciences & Technologies Mohammedia, University Hassan II of Casablanca, Casablanca, Morocco.
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Shang D, Liu Y, Chen Z. Exosome-Transmitted miR-128 Targets CCL18 to Inhibit the Proliferation and Metastasis of Urothelial Carcinoma. Front Mol Biosci 2022; 8:760748. [PMID: 35059433 PMCID: PMC8764124 DOI: 10.3389/fmolb.2021.760748] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/18/2021] [Indexed: 12/26/2022] Open
Abstract
Objective: To investigate the regulatory function of exosome-transmitted miR-128 and chemokine (C-C motif) ligand 18 (CCL18) on urothelial carcinomas (UCs). Methods: Tumor tissues, paracancerous tissues, and serum were collected from 20 patients with UCs (diagnosed at Beijing Friendship Hospital, Capital Medical University). CCL18 was detected by immunohistochemistry and ELISA. PCR was used to measure the expression levels of CCL18 and mir-183, miR-128, mir-33a in UCs. We acquired exosomes from mesenchymal stem cells and synthesized exosomes overexpressing miR-128 (HMSC-128-EV). The effects of miR-128 on the migration and invasion abilities, apoptosis and epithelial-mesenchymal transition of BUC T24 cells were investigated by co-culturing HMSC-128-EV. The therapeutic potential of miR-128 on disease models was explored by injecting HMSC-128-EV into nude mice. Results: The expression of CCL18 in UCs was significantly higher than that in normal tissues (p < 0.05), and the serum level of CCL18 in patients with UC was significantly increased compared with those in healthy controls (p < 0.05). CCL18 overexpression or downregulation enhanced or suppressed the proliferation, migration and invasion of BUC T24 cells, resectively (p < 0.05). The exosome-transmitted miR-128 can inhibit cell proliferation (p < 0.05), invasion (p < 0.05), and migration (p < 0.05) in UCs, and these effects can be reversed by CCL18. In terms of apoptosis, miR-128 was able to promote the occurrence of BUC T24 apoptosis (p < 0.05), which can also be reversed by CCL18. In addition, miR-128 can inhibit the proliferation (p < 0.05) and metastasis (p < 0.05) of UCs in nude mice. Conclusion: The miR-128 inhibits the proliferation, invasion, migration of UCs, and promotes its apoptosis by regulating CCL18 secretion.
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Affiliation(s)
- Donghao Shang
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuting Liu
- Department of Pathology, Capital Medical University, Beijing, China
| | - Zhenghao Chen
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Han J, Yang Z, Zhao S, Zheng L, Tian Y, Lv Y. Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression. Eur J Clin Invest 2021; 51:e13592. [PMID: 34032284 DOI: 10.1111/eci.13592] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression. METHODS The levels of circ_0027599, runt-related transcription factor 1 (RUNX1) mRNA and microRNA-21-5p (miR-21-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The protein levels of RUNX1, E-Cadherin, vimentin and N-Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR-21-5p and the interaction between miR-21-5p and RUNX1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay. RESULTS Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR-21-5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo. CONCLUSION Circ_0027599 overexpression repressed GC progression via modulation of miR-21-5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.
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Affiliation(s)
- Jinzhu Han
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zixin Yang
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shan Zhao
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Likang Zheng
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yanhua Tian
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yingqian Lv
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
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41
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Prashar A, Capurro MI, Jones NL. Under the Radar: Strategies Used by Helicobacter pylori to Evade Host Responses. Annu Rev Physiol 2021; 84:485-506. [PMID: 34672717 DOI: 10.1146/annurev-physiol-061121-035930] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The body depends on its physical barriers and innate and adaptive immune responses to defend against the constant assault of potentially harmful microbes. In turn, successful pathogens have evolved unique mechanisms to adapt to the host environment and manipulate host defenses. Helicobacter pylori (Hp), a human gastric pathogen that is acquired in childhood and persists throughout life, is an example of a bacterium that is very successful at remodeling the host-pathogen interface to promote a long-term persistent infection. Using a combination of secreted virulence factors, immune subversion, and manipulation of cellular mechanisms, Hp can colonize and persist in the hostile environment of the human stomach. Here, we review the most recent and relevant information regarding how this successful pathogen overcomes gastric epithelial host defense responses to facilitate its own survival and establish a chronic infection. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Akriti Prashar
- Program in Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada;
| | - Mariana I Capurro
- Program in Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada;
| | - Nicola L Jones
- Program in Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada; .,Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.,Departments of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, Canada
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42
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Prediction of Blood miRNA-mRNA Regulatory Network in Gastric Cancer. Rep Biochem Mol Biol 2021; 10:243-256. [PMID: 34604414 DOI: 10.52547/rbmb.10.2.243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 10/13/2020] [Indexed: 01/15/2023]
Abstract
Background The aim of the study was to suggest a high specific and sensitive blood biomarker for early GC diagnosis. Methods the expression data of miRNAs and mRNAs were collected from the blood samples of the GC patients based on literature mining. Bioinformatics tools and databases (PANTHER, TargetScan, miRTarBase, miRDB, STRING, and Cytoscape) were used to predict the regulatory relationship. Subsequently, expression level of the selected miRNA was evaluated in the blood samples of gastritis patients to recognize the common miRNA between the GC and gastritis patients. Results Analysis of 40 target genes by MCODE (installed in Cytoscape software) indicated 4 hub genes (WWP1, SKP2, KLHL42, and FBXO11) as a significant cluster in the PPI network related to miR-21, with Node Score Cutoff: 0.2, Degree Cutoff: 2 and K-Core: 2. In addition, the miRNA RT-qPCR results showed that, the expression level of miR-21 was significantly higher in gastritis group compared to the healthy group (p< 0.05). Conclusion the present study clearly demonstrated the increasing level of blood miR-21 among the gastritis patients infected by H. pylori. Therefore, the altered miRNAs, especially overexpression of onco-miRs, may identify a potential link between miRNAs and pathogenesis of the H. pylori-related complications.
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43
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Pian C, Zhang G, Gao L, Fan X, Li F. miR+Pathway: the integration and visualization of miRNA and KEGG pathways. Brief Bioinform 2021; 21:699-708. [PMID: 30649247 DOI: 10.1093/bib/bby128] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 09/29/2018] [Accepted: 11/30/2018] [Indexed: 01/28/2023] Open
Abstract
miRNAs represent a type of noncoding small molecule RNA. Many studies have shown that miRNAs are widely involved in the regulation of various pathways. The key to fully understanding the regulatory function of miRNAs is the determination of the pathways in which the miRNAs participate. However, the major pathway databases such as KEGG only include information regarding protein-coding genes. Here, we redesigned a pathway database (called miR+Pathway) by integrating and visualizing the 8882 human experimentally validated miRNA-target interactions (MTIs) and 150 KEGG pathways. This database is freely accessible at http://www.insect-genome.com/miR-pathway. Researchers can intuitively determine the pathways and the genes in the pathways that are regulated by miRNAs as well as the miRNAs that target the pathways. To determine the pathways in which targets of a certain miRNA or multiple miRNAs are enriched, we performed a KEGG analysis miRNAs by using the hypergeometric test. In addition, miR+Pathway provides information regarding MTIs, PubMed IDs and the experimental verification method. Users can retrieve pathways regulated by an miRNA or a gene by inputting its names.
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Affiliation(s)
- Cong Pian
- Ministry of Agriculture Key Lab of Agricultural Entomology, Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.,Department of Statistics, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China
| | - Guangle Zhang
- Department of Mathematics, College of Science, Nanjing Agricultural University, Nanjing, Jiangsu, China
| | - Libin Gao
- Ministry of Agriculture Key Lab of Agricultural Entomology, Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China
| | - Xiaodan Fan
- Department of Statistics, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China
| | - Fei Li
- Ministry of Agriculture Key Lab of Agricultural Entomology, Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China
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44
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Tito C, De Falco E, Rosa P, Iaiza A, Fazi F, Petrozza V, Calogero A. Circulating microRNAs from the Molecular Mechanisms to Clinical Biomarkers: A Focus on the Clear Cell Renal Cell Carcinoma. Genes (Basel) 2021; 12:1154. [PMID: 34440329 PMCID: PMC8391131 DOI: 10.3390/genes12081154] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/26/2021] [Accepted: 07/26/2021] [Indexed: 02/06/2023] Open
Abstract
microRNAs (miRNAs) are emerging as relevant molecules in cancer development and progression. MiRNAs add a post-transcriptional level of control to the regulation of gene expression. The deregulation of miRNA expression results in changing the molecular circuitry in which miRNAs are involved, leading to alterations of cell fate determination. In this review, we describe the miRNAs that are emerging as innovative molecular biomarkers from liquid biopsies, not only for diagnosis, but also for post-surgery management in cancer. We focus our attention on renal cell carcinoma, in particular highlighting the crucial role of circulating miRNAs in clear cell renal cell carcinoma (ccRCC) management. In addition, the functional deregulation of miRNA expression in ccRCC is also discussed, to underline the contribution of miRNAs to ccRCC development and progression, which may be relevant for the identification and design of innovative clinical strategies against this tumor.
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Affiliation(s)
- Claudia Tito
- Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy; (C.T.); (A.I.); (F.F.)
| | - Elena De Falco
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
- Mediterranea Cardiocentro, 80122 Naples, Italy
| | - Paolo Rosa
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
| | - Alessia Iaiza
- Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy; (C.T.); (A.I.); (F.F.)
| | - Francesco Fazi
- Department of Anatomical, Histological, Forensic & Orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy; (C.T.); (A.I.); (F.F.)
| | - Vincenzo Petrozza
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
| | - Antonella Calogero
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy; (E.D.F.); (P.R.); (V.P.)
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Abstract
Gastric cancer (GC) is one of the most common malignant tumors. The mechanism of how GC develops is vague, and therapies are inefficient. The function of microRNAs (miRNAs) in tumorigenesis has attracted the attention from many scientists. During the development of GC, miRNAs function in the regulation of different phenotypes, such as proliferation, apoptosis, invasion and metastasis, drug sensitivity and resistance, and stem-cell-like properties. MiRNAs were evaluated for use in diagnostic and prognostic predictions and exhibited considerable accuracy. Although many problems exist for the application of therapy, current studies showed the antitumor effects of miRNAs. This paper reviews recent advances in miRNA mechanisms in the development of GC and the potential use of miRNAs in the diagnosis and treatment of GC.
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46
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Doldi V, El Bezawy R, Zaffaroni N. MicroRNAs as Epigenetic Determinants of Treatment Response and Potential Therapeutic Targets in Prostate Cancer. Cancers (Basel) 2021; 13:2380. [PMID: 34069147 PMCID: PMC8156532 DOI: 10.3390/cancers13102380] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/07/2021] [Accepted: 05/13/2021] [Indexed: 12/15/2022] Open
Abstract
Prostate cancer (PCa) is the second most common tumor in men worldwide, and the fifth leading cause of male cancer-related deaths in western countries. PC is a very heterogeneous disease, meaning that optimal clinical management of individual patients is challenging. Depending on disease grade and stage, patients can be followed in active surveillance protocols or undergo surgery, radiotherapy, hormonal therapy, and chemotherapy. Although therapeutic advancements exist in both radiatiotherapy and chemotherapy, in a considerable proportion of patients, the treatment remains unsuccessful, mainly due to tumor poor responsiveness and/or recurrence and metastasis. microRNAs (miRNAs), small noncoding RNAs that epigenetically regulate gene expression, are essential actors in multiple tumor-related processes, including apoptosis, cell growth and proliferation, autophagy, epithelial-to-mesenchymal transition, invasion, and metastasis. Given that these processes are deeply involved in cell response to anti-cancer treatments, miRNAs have been considered as key determinants of tumor treatment response. In this review, we provide an overview on main PCa-related miRNAs and describe the biological mechanisms by which specific miRNAs concur to determine PCa response to radiation and drug therapy. Additionally, we illustrate whether miRNAs can be considered novel therapeutic targets or tools on the basis of the consequences of their expression modulation in PCa experimental models.
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Affiliation(s)
| | | | - Nadia Zaffaroni
- Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (V.D.); (R.E.B.)
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47
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Wang C, Hu Y, Yang H, Wang S, Zhou B, Bao Y, Huang Y, Luo Q, Yang C, Xie X, Yang S. Function of Non-coding RNA in Helicobacter pylori-Infected Gastric Cancer. Front Mol Biosci 2021; 8:649105. [PMID: 34046430 PMCID: PMC8144459 DOI: 10.3389/fmolb.2021.649105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer is a common malignant tumor of the digestive system. Its occurrence and development are the result of a combination of genetic, environmental, and microbial factors. Helicobacter pylori infection is a chronic infection that is closely related to the occurrence of gastric tumorigenesis. Non-coding RNA has been demonstrated to play a very important role in the organism, exerting a prominent role in the carcinogenesis, proliferation, apoptosis, invasion, metastasis, and chemoresistance of tumor progression. H. pylori infection affects the expression of non-coding RNA at multiple levels such as genetic polymorphisms and signaling pathways, thereby promoting or inhibiting tumor progression or chemoresistance. This paper mainly introduces the relationship between H. pylori-infected gastric cancer and non-coding RNA, providing a new perspective for gastric cancer treatment.
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Affiliation(s)
- Chao Wang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yiyang Hu
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Huan Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Sumin Wang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Bo Zhou
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yulu Bao
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yu Huang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Qiang Luo
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Chuan Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Xia Xie
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
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48
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Nichols RG, Davenport ER. The relationship between the gut microbiome and host gene expression: a review. Hum Genet 2021; 140:747-760. [PMID: 33221945 PMCID: PMC7680557 DOI: 10.1007/s00439-020-02237-0] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/06/2020] [Indexed: 12/13/2022]
Abstract
Despite the growing knowledge surrounding host-microbiome interactions, we are just beginning to understand how the gut microbiome influences-and is influenced by-host gene expression. Here, we review recent literature that intersects these two fields, summarizing themes across studies. Work in model organisms, human biopsies, and cell culture demonstrate that the gut microbiome is an important regulator of several host pathways relevant for disease, including immune development and energy metabolism, and vice versa. The gut microbiome remodels host chromatin, causes differential splicing, alters the epigenetic landscape, and directly interrupts host signaling cascades. Emerging techniques like single-cell RNA sequencing and organoid generation have the potential to refine our understanding of the relationship between the gut microbiome and host gene expression in the future. By intersecting microbiome and host gene expression, we gain a window into the physiological processes important for fostering the extensive cross-kingdom interactions and ultimately our health.
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Affiliation(s)
- Robert G. Nichols
- Department of Biology, The Pennsylvania State University, University Park, PA 16802 USA
| | - Emily R. Davenport
- Department of Biology, The Pennsylvania State University, University Park, PA 16802 USA
- Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802 USA
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49
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Zhou X, Cao H, Zeng Y. Microfluidic circulating reactor system for sensitive and automated duplex-specific nuclease-mediated microRNA detection. Talanta 2021; 232:122396. [PMID: 34074392 DOI: 10.1016/j.talanta.2021.122396] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/31/2021] [Accepted: 04/01/2021] [Indexed: 12/27/2022]
Abstract
Duplex-specific nuclease signal amplification (DSNSA) is a promising microRNA (miRNA) quantification strategy. However, existing DSNSA based miRNA detection methods suffer from costly chemical consumptions and require laborious multi-step sample pretreatment that are prone to sample loss and contamination, including total RNA extraction and enrichment. To address these problems, herein we devised a pneumatically automated microfluidic reactor device that integrates both analyte extraction/enrichment and DSNSA-mediated miRNA detection in one streamlined analysis workflow. Two flow circulation strategies were investigated to determine the effects of flow conditions on the kinetics of on-chip DSNSA reaction in a bead-packed microreactor. With the optimized workflow, we demonstrated rapid, robust on-chip detection of miR-21 with a limit-of-detection of 35 amol, while greatly reducing the consumption of DSN enzyme to 0.1 U per assay. Therefore, this microfluidic system provides a useful tool for many applications, including clinical diagnosis.
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Affiliation(s)
- Xin Zhou
- Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA
| | - Hongmei Cao
- Department of Chemistry, University of Kansas, Lawrence, KS, 66045, USA
| | - Yong Zeng
- Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA; University of Florida Health Cancer Center, Gainesville, FL, 32610, USA.
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50
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Baghery Saghchy Khorasani A, Pourbagheri-Sigaroodi A, Pirsalehi A, Safaroghli-Azar A, Zali MR, Bashash D. The PI3K/Akt/mTOR signaling pathway in gastric cancer; from oncogenic variations to the possibilities for pharmacologic interventions. Eur J Pharmacol 2021; 898:173983. [PMID: 33647255 DOI: 10.1016/j.ejphar.2021.173983] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 02/13/2021] [Accepted: 02/23/2021] [Indexed: 12/24/2022]
Abstract
Genetic and epigenetic alterations have been under concentrated investigations for many years in order to unearth the molecules regulating human cancer pathogenesis. However, the identification of a wide range of dysregulated genes and their protein products has raised a question regarding how the results of this large collection of alterations could converge into a formation of one malignancy. The answer may be found in the signaling cascades that regulate the survival and metabolism of the cells. Aberrancies of each participant molecule of such cascades may well result in augmented viability and unlimited proliferation of cancer cells. Among various signaling pathways, the phosphatidylinositol-3-kinase (PI3K) axis has been shown to be activated in about one-third of human cancers. One of the malignancies that is mostly affected by this axis is gastric cancer (GC), one of the most fatal cancers worldwide. In the present review, we aimed to illustrate the significance of the PI3K/Akt/mTOR axis in the pathogenesis of GC and also provided a wide perspective about the application of the inhibitors of this axis in the therapeutic strategies of this malignancy.
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Affiliation(s)
| | - Atieh Pourbagheri-Sigaroodi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Pirsalehi
- Department of Internal Medicine, School of Medicine, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ava Safaroghli-Azar
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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