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Fabijanec M, Hulina-Tomašković A, Štefanović M, Verbanac D, Ćelap I, Somborac-Bačura A, Grdić Rajković M, Demirović A, Ramić S, Krušlin B, Rumora L, Čeri A, Koržinek M, Petrik J, Ljubičić N, Baršić N, Barišić K. MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients. Int J Mol Sci 2024; 25:8156. [PMID: 39125725 PMCID: PMC11311302 DOI: 10.3390/ijms25158156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/16/2024] [Accepted: 07/22/2024] [Indexed: 08/12/2024] Open
Abstract
Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker.
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Affiliation(s)
- Marija Fabijanec
- Center for Applied Medical Biochemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia;
| | - Andrea Hulina-Tomašković
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Mario Štefanović
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
- Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia
| | - Donatella Verbanac
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Ivana Ćelap
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
- Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia
| | - Anita Somborac-Bačura
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Marija Grdić Rajković
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Alma Demirović
- Department of Pathology and Cytology “Ljudevit Jurak”, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (A.D.); (B.K.)
| | - Snježana Ramić
- Department of Oncological Pathology, University Hospital for Tumors, Sestre Milosrdnice University Hospital Centre, 10000 Zagreb, Croatia;
| | - Božo Krušlin
- Department of Pathology and Cytology “Ljudevit Jurak”, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (A.D.); (B.K.)
| | - Lada Rumora
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Andrea Čeri
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Martha Koržinek
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - József Petrik
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Neven Ljubičić
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (N.L.)
| | - Neven Baršić
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (N.L.)
| | - Karmela Barišić
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
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Solanki R, Zubbair Malik M, Alankar B, Ahmad FJ, Dohare R, Chauhan R, Kesharwani P, Kaur H. Identification of novel biomarkers and potential molecular targets for uterine cancer using network-based approach. Pathol Res Pract 2024; 260:155431. [PMID: 39029376 DOI: 10.1016/j.prp.2024.155431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/20/2024] [Accepted: 06/26/2024] [Indexed: 07/21/2024]
Abstract
A better understanding of incidences at the cellular level in uterine cancer is necessary for its effective treatment and favourable prognosis. Till date, it lacks appropriate molecular target-based treatment because of unknown molecular mechanisms that proceed to cancer and no drug has shown the required results of treatment with less severe side effects. Uterine Cancer is one of the top five cancer diagnoses and among the ten most common death-causing cancer in the United States of America. There is no FDA-approved drug for it yet. Therefore, it became necessary to identify the molecular targets for molecular targeted therapy of this widely prevalent cancer type. For this study, we used a network-based approach to the list of the deregulated (both up and down-regulated) genes taking adjacent p-Value ≤ 0.05 as significance cut off for the mRNA data of uterine cancer. We constructed the protein-protein interaction (PPI) network and analyzed the degree, closeness, and betweenness centrality-like topological properties of the PPI network. Then we traced the top 30 genes listed from each topological property to find the key regulators involved in the endometrial cancer (ECa) network. We then detected the communities and sub-communities from the PPI network using the Cytoscape network analyzer and Louvain modularity optimization method. A set of 26 (TOP2A, CENPE, RAD51, BUB1, BUB1B, KIF2C, KIF23, KIF11, KIF20A, ASPM, AURKA, AURKB, PLK1, CDC20, CDKN2A, EZH2, CCNA2, CCNB1, CDK1, FGF2, PRKCA, PGR, CAMK2A, HPGDS, and CDCA8) genes were found to be key genes of ECa regulatory network altered in disease state and might be playing the regulatory role in complex ECa network. Our study suggests that among these genes, KIF11 and H PGDS appeared to be novel key genes identified in our research. We also identified these key genes interactions with miRNAs.
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Affiliation(s)
- Rubi Solanki
- School of Interdisciplinary Sciences and Technology, Jamia Hamdard, New Delhi 110062, India
| | - Md Zubbair Malik
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute Dasman 15462, Kuwait
| | - Bhavya Alankar
- Department of Computer Science and Engineering, School of Engineering Sciences and Technology, Jamia Hamdard, New Delhi 110062, India.
| | - Farhan Jalees Ahmad
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Ravins Dohare
- Centre for Interdisciplinary Research in Basic Sciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India
| | - Ritu Chauhan
- Artificial Intelligence and IoT lab, Centre for Computational Biology and Bioinformatics, Amity University, Noida, India
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
| | - Harleen Kaur
- Department of Computer Science and Engineering, School of Engineering Sciences and Technology, Jamia Hamdard, New Delhi 110062, India.
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Gherman A, Bolundut D, Ecea R, Balacescu L, Curcean S, Dina C, Balacescu O, Cainap C. Molecular Subtypes, microRNAs and Immunotherapy Response in Metastatic Colorectal Cancer. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:397. [PMID: 38541123 PMCID: PMC10972200 DOI: 10.3390/medicina60030397] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 02/10/2024] [Accepted: 02/18/2024] [Indexed: 11/12/2024]
Abstract
Currently, only a limited set of molecular traits are utilized to direct treatment for metastatic CRC (mCRC). The molecular classification of CRC depicts tumor heterogeneity based on gene expression patterns and aids in comprehending the biological characteristics of tumor formation, growth and prognosis. Additionally, it assists physicians in tailoring the therapeutic approach. Microsatellite instability (MSI-H)/deficient mismatch repair proteins (MMRd) status has become a ubiquitous biomarker in solid tumors, caused by mutations or methylation of genes and, in turn, the accumulation of mutations and antigens that subsequently induce an immune response. Immune checkpoint inhibitors (ICI) have recently received approval for the treatment of mCRC with MSI-H/MMRd status. However, certain individuals experience either initial or acquired resistance. The tumor-programmed cell death ligand 1 (PD-L1) has been linked to the ability of CRC to evade the immune system and promote its growth. Through comprehensive research conducted via the PUBMED database, the objectives of this paper were to review the molecular characteristics linked to tumor response in metastatic CRC in light of improved patients' outcomes following ICI therapies as seen in clinical trials and to identify particular microRNAs that can modulate the expression of specific oncoproteins, such as PD-L1, and disrupt the mechanisms that allow the immune system to be evaded.
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Affiliation(s)
- Alexandra Gherman
- 10th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania; (A.G.); (C.C.)
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania; (D.B.); (R.E.)
| | - Dinu Bolundut
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania; (D.B.); (R.E.)
| | - Radu Ecea
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania; (D.B.); (R.E.)
| | - Loredana Balacescu
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania;
| | - Sebastian Curcean
- 10th Department of Radiation Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania;
- Department of Radiation Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Constantin Dina
- Department of Anatomy, Faculty of Medicine, Ovidius University, 124 Mamaia Boulevard, 900527 Constanta, Romania
| | - Ovidiu Balacescu
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania;
| | - Calin Cainap
- 10th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania; (A.G.); (C.C.)
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania; (D.B.); (R.E.)
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Liu X, Zhang L. microRNA-92b-3p augments colon cancer development through inhibiting KLF3. J Biochem Mol Toxicol 2023; 37:e23488. [PMID: 37597242 DOI: 10.1002/jbt.23488] [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: 02/22/2023] [Revised: 07/05/2023] [Accepted: 07/31/2023] [Indexed: 08/21/2023]
Abstract
Colon cancer (CC) is a tumor of the large intestine. miR-92b-3p is often deregulated in the tumorigensis. Here, the role of miR-92b-3p in the development of CC was investigated. miR-92b-3p and Kruppel-like factor 3 (KLF3) expression was examined in CC tissues and cells. miR-92b-3p inhibitor or KLF3 overexpression vector was transfected into CC cells, respectively to observe its role in CC cell proliferation, invasion, migration, and apoptosis. The targeting relationship between miR-92b-3p and KLF3 was validated. Meanwhile, rescue experiments were performed by co-transfection of miR-92b-3p inhibitor and KLF3 siRNA, followed by determining CC cell proliferation, invasion, migration, and apoptosis. Higher miR-92b-3p and lower KLF3 expression levels were observed in CC tissues and cells. miR-92b-3p inhibition or KLF3 overexpression reduced proliferation, invasion, and migration whereas induced apoptosis of CC cells. KLF3 was validated to be the target gene of miR-92b-3p. Depletion of KLF3 could reverse the antitumor role of miR-92b-3p inhibition in CC cells. miR-92b-3p augments CC development through inhibiting KLF3, which may confers a novel way to develop future treatment target.
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Affiliation(s)
- Xuezhong Liu
- Department of Gastrointestinal Surgery, Liaocheng People's Hospital, Liaocheng, Shandong, China
| | - Lei Zhang
- Department of General Surgery, Liaocheng Dongchangfu People's Hospital, Liaocheng, Shandong, China
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Zhang Y, Wang Y, Zhang B, Li P, Zhao Y. Methods and biomarkers for early detection, prediction, and diagnosis of colorectal cancer. Biomed Pharmacother 2023; 163:114786. [PMID: 37119736 DOI: 10.1016/j.biopha.2023.114786] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/17/2023] [Accepted: 04/24/2023] [Indexed: 05/01/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common digestive diseases worldwide. It has steadily ascended to the top three cancers in terms of incidence and mortality. The primary cause is the inability to diagnose it at an early stage. Therefore, early detection and diagnosis are essential for colorectal cancer prevention. Although there are now various methods for CRC early detection, in addition to recent developments in surgical and multimodal therapy, the poor prognosis and late detection of CRC still remain significant. Thus, it is important to investigate novel technologies and biomarkers to improve the sensitization and specification of CRC diagnosis. Here, we present some common methods and biomarkers for early detection and diagnosis of CRC, we hope this review will encourage the adoption of screening programs and the clinical use of these potential molecules as biomarkers for CRC early detection and prognosis.
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Affiliation(s)
- Yue Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yin Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China; Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province affiliated to Qingdao University, Shandong Province, China
| | - Bingqiang Zhang
- Key Laboratory of Cancer and Immune Cells of Qingdao, Qingdao 266021, China
| | - Peifeng Li
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China.
| | - Yi Zhao
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China.
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Gherman A, Balacescu L, Popa C, Cainap C, Vlad C, Cainap SS, Balacescu O. Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer. Int J Mol Sci 2023; 24:10622. [PMID: 37445798 DOI: 10.3390/ijms241310622] [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: 05/03/2023] [Revised: 06/10/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4-6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (p = 0.007 **), miR-146a-5p (p = 0.036 *), miR-221-3p (p = 0.047 *), and miR-484 (p = 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (p = 0.008 **), miR-143-3p (p = 0.009 **), miR-221-3p (p = 0.016 *), and miR-486-5p (p = 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (p = 0.003 **) and miR-486-5p (p = 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.
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Affiliation(s)
- Alexandra Gherman
- 11th Department of Medical Oncology, University of Medicine and Pharmacy "Iuliu Hatieganu", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
- Department of Medical Oncology, The Oncology Institute "Prof. Dr. Ion Chiricuta", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Loredana Balacescu
- 11th Department of Medical Oncology, University of Medicine and Pharmacy "Iuliu Hatieganu", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. Ion Chiricuta", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Calin Popa
- "Prof. Dr. Octavian Fodor" Regional Institute of Gastroenterology and Hepatology Cluj-Napoca, 19-21 Croitorilor Street, 400162 Cluj-Napoca, Romania
- Department of Surgery, Surgery Unit No 3, University of Medicine and Pharmacy "Iuliu Hațieganu" Cluj-Napoca, 19-21 Croitorilor Street, 400162 Cluj-Napoca, Romania
| | - Calin Cainap
- 11th Department of Medical Oncology, University of Medicine and Pharmacy "Iuliu Hatieganu", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
- Department of Medical Oncology, The Oncology Institute "Prof. Dr. Ion Chiricuta", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Catalin Vlad
- Department of Surgery, The Oncology Institute "Prof. Dr. Ion Chiricuta", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
- Department of Oncology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
| | - Simona S Cainap
- Department of Mother and Child, Pediatric Cardiology, University of Medicine and Pharmacy "Iuliu Hatieganu", 19-21 Croitorilor Street, 400162 Cluj-Napoca, Romania
- Department of Paediatric Cardiology, Pediatric Clinic No 2, Emergency County Hospital for Children, 68 Motilor Street, 400370 Cluj-Napoca, Romania
| | - Ovidiu Balacescu
- 11th Department of Medical Oncology, University of Medicine and Pharmacy "Iuliu Hatieganu", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. Ion Chiricuta", 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
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Gao Y, Zhang J, Pan J, Ying S, Lou B, Yang Q, Hong W, Yang G. F OF1-ATP synthase molecular motor biosensor for miRNA detection of colon cancer. Life Sci 2023; 319:121527. [PMID: 36841472 DOI: 10.1016/j.lfs.2023.121527] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 02/11/2023] [Accepted: 02/20/2023] [Indexed: 02/27/2023]
Abstract
AIMS To establish a FOF1-ATP synthase molecular motor biosensor to accurately identify colon cancer miRNAs. MAIN METHODS The FOF1-ATP synthase molecular motor is extracted by fragmentation-centrifugation and connected to the colon cancer-specific miR-17 capture probe in the manner of the ε subunit-biotin-streptavidin-biotin system. Signal probes are designed for dual-signal characterization to increase detection accuracy. The FOF1-ATPase rotation rate decreases when the signaling and capture probes are combined with the target miRNA, resulting in a decrease in ATP synthesis. miR-17 concentrations are determined by changes in ATP-mediated chemiluminescence intensity and signal probe-mediated OD450nm. KEY FINDINGS The chemiluminescence intensity and OD450nm show a good linear relationship with the miR-17 concentration in the range of 5 to 200 nmol L-1 (R2 = 0.9985, 0.9989). The colon cancer mouse model is established for the blood samples, and miR-17 in serum and RNA extracts is quantitatively determined using the constructed sensor. SIGNIFICANCE The results are consistent with colon cancer progression, and the low concentration of miR-17 detecting accuracy is comparable to the PCR assay. In conclusion, the developed method is a direct, rapid, and promising method for miRNA detection of colon cancer.
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Affiliation(s)
- Ying Gao
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China; Zhejiang Moda Biotech Co., Ltd, Hangzhou 310018, China
| | - Jie Zhang
- Taizhou Technician College, Taizhou 318000, China
| | - Jiexia Pan
- Criminal Investigation Corps of Zhejiang Provincial Public Security Department, Hangzhou 310009, China
| | - Sanjun Ying
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China
| | - Bang Lou
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China
| | - Qingliang Yang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China
| | - Weiyong Hong
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China; Department of Pharmacy, Municipal Hospital Affiliated to Taizhou University, Taizhou 318000, China.
| | - Gensheng Yang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China.
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Mirzajani E, Vahidi S, Norollahi SE, Samadani AA. Novel biomarkers of microRNAs in gastric cancer; an overview from diagnosis to treatment. Microrna 2022; 11:12-24. [PMID: 35319404 DOI: 10.2174/2211536611666220322160242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/06/2021] [Accepted: 12/28/2021] [Indexed: 11/22/2022]
Abstract
The fourth frequent disease in the world and the second cause of cancer-related death is gastric cancer (GC). In this way, over 80% of diagnoses are made in the middle to advanced degrees of the disease, underscoring the requirement for innovative biomarkers that can be identified quickly. Meaningly, biomarkers that can complement endoscopic diagnosis and be used to detect patients with a high risk of GC are desperately needed. These biomarkers will allow for the accurate prediction of therapy response and prognosis in GC patients, as well as the development of an optimal treatment strategy for each individual. Conspicoiusly, microRNAs (miRNAs) and small noncoding RNA regulates the expression of target mRNA and thereby modifies critical biological mechanisms. According to the data, abnormally miRNAs expression in GC is linked to tumor growth, carcinogenesis, aggression and distant metastasis. Importantly, miRNA expression patterns and next-generation sequencing (NGS) can also be applied to analyze kinds of tissues and cancers. Given the high death rates and poor prognosis of GC, and the absence of a clinical diagnostic factor that is adequately sensitive to GC, research into novel sensitive and specific markers for GC diagnosis is critical. In this review,we evaluate the latest research findings that suggest the feasibility and clinical utility of miRNAs in GC.
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Affiliation(s)
- Ebrahim Mirzajani
- Department of Biochemistry, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Sogand Vahidi
- Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Seyedeh Elham Norollahi
- Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Ali Akbar Samadani
- Guilan Road Trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran
- Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
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9
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Kao WY, Yang CL, Tsai FM, Chen CW, Hsiao KH, Chen JH. Comparing miR-16 and miR-1228 as an optimal endogenous control for quantification of circulating microRNAs in colorectal cancer patients. Tzu Chi Med J 2022; 34:318-322. [PMID: 35912051 PMCID: PMC9333100 DOI: 10.4103/tcmj.tcmj_240_21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/08/2021] [Accepted: 12/20/2021] [Indexed: 11/06/2022] Open
Abstract
Objectives: Circulating microRNAs (miRNAs) have been discovered to play a novel role in intercellular communication and cancer biology. They are emerging candidates for noninvasive molecular biomarkers of cancer and other diseases. However, current translational researches have been limited by the lack of consensus on the optimal endogenous control of circulating miRNAs quantitation. In this study, we compared two promising miRNAs, miR-1228 and miR-16, as an endogenous control. The effects of normalizers on the relative quantification of circulating miR-31 in plasma samples of colorectal cancer (CRC) were also assessed. Materials and Methods: The cel-miR-39 was a spiked-in RNA used as an external control and added to plasma samples before RNA extraction. Quantitative real-time polymerase chain reaction technology was used to analyze the expression levels of circulating miRNAs in plasma samples of 4 healthy controls and 14 CRC patients. The expression stability of the candidate controls was compared by Ct analysis and NormFinder algorithms. Results: There was no significant difference in expression level of miR-16 and miR-1228 between healthy control group and before or after therapy of CRC patient groups. The expression of miR-1228 has smaller the range Ct values (28.25-25.64)compared with those of miR-16 (24.91-20.34). The stability value of miR-1228 (0.102) is lower than that of miR-16 (0.350). The expression of miR-1228 endogenous reference candidate has lower stability value and smaller the range Ct values compared with those in miR-16. According to the range Ct values and stability value, miR-1228 is better than miR-16 as endogenous control in CRC patients. There are significant differences in circulating miR-31 expression between healthy control and CRC patients when miR-1228 was used to standardize miR-31 expression. Conclusions: miR-1228 is recommended as a better endogenous control in quantification of circulating miRNAs in CRC patients.
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10
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Liu S, Chu L, Xie M, Ma L, An H, Zhang W, Deng J. miR-92a-3p Promoted EMT via Targeting LATS1 in Cervical Cancer Stem Cells. Front Cell Dev Biol 2021; 9:757747. [PMID: 34869346 PMCID: PMC8639224 DOI: 10.3389/fcell.2021.757747] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/26/2021] [Indexed: 01/19/2023] Open
Abstract
miR-92a-3p (microRNA-92a-3p) has been reported to be dysregulated in several cancers, and as such, it is considered to be a cancer-related microRNA. However, the influence of miR-92a-3p on biological behaviors in cervical cancer (CC) still remains unclear. Quantitative real-time PCR was used to detect miR-92a-3p levels in CC stem cells. Here, Cell Counting Kit-8 (CCK8) assay, Transwell cell invasion assay and flow cytometry assay were used to characterize the effects that miR-92a-3p and large tumor suppressor l (LATS1) had on proliferation, invasion and cell cycle transition. The luciferase reporter gene assay was used to verify the targeting relationship between miR-92a-3p and LATS1. Western Blotting was used to investigate the related signaling pathways and proteins. Data from The Cancer Genome Atlas (TCGA) showed that miR-92a-3p was upregulated in CC tissues and closely associated with overall survival. miR-92a-3p promoted proliferation, invasion and cell cycle transition in CC stem cells. The luciferase reporter assay showed that miR-92a-3p bound to the 3′-untranslated region (3′-UTR) of the LATS1 promoter. LATS1 inhibited proliferation, invasion and cell cycle transition. Results measured by Western Blotting showed that LATS1 downregulated expressions of transcriptional co-activator with PDZ-binding motif (TAZ), vimentin and cyclin E, but upregulated the expression of E-cadherin. Re-expression of LATS1 partly reversed the effects of miR-92a-3p on proliferation, invasion and cell cycle transition, as well as on TAZ, E-cadherin, vimentin, and cyclin E. miR-92a-3p promoted the malignant behavior of CC stem cells by targeting LATS1, which regulated TAZ and E-cadherin.
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Affiliation(s)
- Shuangyue Liu
- Department of Gynecology, Kunming Maternity and Child Care Hospital, Kunming, China
| | - Liping Chu
- Department of Gynecology, Kunming Maternity and Child Care Hospital, Kunming, China
| | - Mingzhu Xie
- Department of Gynecology, Kunming Maternity and Child Care Hospital, Kunming, China
| | - Lisha Ma
- Department of Gynecology, Kunming Maternity and Child Care Hospital, Kunming, China
| | - Hongmei An
- Department of Gynecology, Kunming Maternity and Child Care Hospital, Kunming, China
| | - Wen Zhang
- Department of Gynecology, Kunming Maternity and Child Care Hospital, Kunming, China
| | - Jihong Deng
- Department of Gynecology, Kunming Maternity and Child Care Hospital, Kunming, China
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11
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Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13153892. [PMID: 34359796 PMCID: PMC8345682 DOI: 10.3390/cancers13153892] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/23/2021] [Accepted: 07/26/2021] [Indexed: 12/24/2022] Open
Abstract
In colorectal cancer (CRC), 20-50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II-IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32-11.69); 3.72 (1.99-6.95); 2.58 (1.18-5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64-5.73); 3.41 (1.55-7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38-7.04) and OS, HR 3.20 (1.39-7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0-53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.
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12
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Pidíková P, Herichová I. miRNA Clusters with Up-Regulated Expression in Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13122979. [PMID: 34198662 PMCID: PMC8232258 DOI: 10.3390/cancers13122979] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/05/2021] [Accepted: 06/09/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary As miRNAs show the capacity to be used as CRC biomarkers, we analysed experimentally validated data about frequently up-regulated miRNA clusters in CRC tissue. We identified 15 clusters that showed increased expression in CRC: miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224. Cluster positions in the genome are intronic or intergenic. Most clusters are regulated by several transcription factors, and by long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. The members of the selected clusters target 181 genes. Their functions and corresponding pathways were revealed with the use of Panther analysis. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research. Abstract Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.
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13
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Li M, Shan W, Hua Y, Chao F, Cui Y, Lv L, Dou X, Bian X, Zou J, Li H, Lin W. Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway. Front Cell Dev Biol 2021; 9:661602. [PMID: 34136482 PMCID: PMC8201786 DOI: 10.3389/fcell.2021.661602] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 04/19/2021] [Indexed: 12/13/2022] Open
Abstract
Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never been explored. In this study, we observed that the expression of exosomal miR-92b-3p was significantly increased in patients who developed chemoresistance. Luciferase reporter analysis confirmed that PTEN was a target gene of miR-92b-3p. The PTEN/AKT regulatory network was related to miR-92b-3p-mediated cell migration and chemoresistance in vitro and in vivo in SCLC. Importantly, exosomes isolated from the conditioned medium of SBC-3 cells overexpressing miR-92b-3p could promote SCLC chemoresistance and cell migration. Furthermore, we found that plasma miR-92b-3p levels were significantly higher in patients with chemoresistant SCLC than in those with chemosensitive SCLC, but the levels were down-regulated in patients who achieved remission. Kaplan–Meier analysis showed that SCLC patients with high miR-92b-3p expression were associated with shorter progression-free survival. Overall, our results suggested that exosomal miR-92b-3p is a potential dynamic biomarker to monitor chemoresistance in SCLC and represents a promising therapeutic target for chemoresistant SCLC.
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Affiliation(s)
- Ming Li
- Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Wulin Shan
- Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Yan Hua
- Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Fengmei Chao
- Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Yayun Cui
- Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Lei Lv
- Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Xiaoyan Dou
- Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Xing Bian
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Jinglu Zou
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Hong Li
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Wenchu Lin
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
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14
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Faraldi M, Gerosa L, Gomarasca M, Sansoni V, Perego S, Ziemann E, Banfi G, Lombardi G. A Physically Active Status Affects the Circulating Profile of Cancer-Associated miRNAs. Diagnostics (Basel) 2021; 11:diagnostics11050820. [PMID: 33946605 PMCID: PMC8147229 DOI: 10.3390/diagnostics11050820] [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: 03/24/2021] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
Circulating miRNAs are ideal diagnostics and prognostics biomarkers in cancer since altered levels of specific miRNAs have been associated to development/progression of several cancers. Physical activity is a recognized preventive strategy against several cancers, but it may also modify the baseline levels of cancer-associated miRNAs and, hence, may act as a confounding pre-analytical variable. This study aimed at understanding whether physical activity-dependent changes in cancer-associated circulating miRNAs profile could act as a confounding variable. A panel comprising 179 miRNAs was assayed in plasma from 20 highly trained and 10 sedentary men. RT-qPCR data were analyzed with the 2−2ΔΔCT methods and normalized on hsa-miR-320d, as determined by bioinformatics analysis. miRNAs associated with the diagnosis of the most prevalent cancers were considered. Only those miRNAs, relevantly associated with cancers, found ≥2-fold up- or downregulated in highly trained subjects compared to sedentary were disclosed. The results reveal that chronic physical activity determined modifications altering the baseline level of several cancer-associated miRNAs and, hence, their diagnostic and prognostic potential. In conclusion, based on our results, a physically active status emerges as an important pre-analytical variable able to alter the basal level of circulating miRNAs, and these alterations might be considered as potentially misleading the analytical output.
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Affiliation(s)
- Martina Faraldi
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy; (M.F.); (M.G.); (V.S.); (S.P.); (G.B.); (G.L.)
| | - Laura Gerosa
- Gruppo San Donato Foundation, 20122 Milano, Italy
- Correspondence: ; Tel.: +39-02166214068
| | - Marta Gomarasca
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy; (M.F.); (M.G.); (V.S.); (S.P.); (G.B.); (G.L.)
| | - Veronica Sansoni
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy; (M.F.); (M.G.); (V.S.); (S.P.); (G.B.); (G.L.)
| | - Silvia Perego
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy; (M.F.); (M.G.); (V.S.); (S.P.); (G.B.); (G.L.)
| | - Ewa Ziemann
- Department of Athletics, Strength and Conditioning, Poznań University of Physical Education, 61-871 Poznań, Poland;
| | - Giuseppe Banfi
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy; (M.F.); (M.G.); (V.S.); (S.P.); (G.B.); (G.L.)
- Vita-Salute San Raffaele University, 20132 Milano, Italy
| | - Giovanni Lombardi
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy; (M.F.); (M.G.); (V.S.); (S.P.); (G.B.); (G.L.)
- Department of Athletics, Strength and Conditioning, Poznań University of Physical Education, 61-871 Poznań, Poland;
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15
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Paciorek P, Żuberek M, Grzelak A. Rola miRNA w rozwoju wybranych nowotworów – potencjalne zastosowanie w diagnostyce*. POSTEP HIG MED DOSW 2021. [DOI: 10.5604/01.3001.0014.6578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Streszczenie
MikroRNA (miRNA) są małymi cząsteczkami kwasu rybonukleinowego, które mimo że nie podlegają procesowi translacji, pełnią ważną funkcję regulacyjną w komórkach eukariotycznych. Ich fizjologiczną funkcją jest utrzymywanie homeostazy komórek. Zaburzona ekspresja miRNA może spowodować rozwój wielu chorób, w tym chorób nowotworowych. Działanie miRNA polega na hamowaniu tworzenia się białek, w tym białek o właściwościach onkogennych i antyonkogennych. Mutacje w miejscach kodowania miRNA mogą prowadzić do nadmiernego lub zmniejszonego wytwarzania wspomnianych białek. Odkrycie miRNA i poznanie ich roli w komórce otworzyło nowe możliwości dla diagnostyki chorób nowotworowych. Zmiany poziomu odpowiednich miRNA, w krwiobiegu lub innych płynach ustrojowych, mogą być markerem diagnostycznym chorób. Diagnostyka onkologiczna mogłaby przebiegać na podstawie badań profilu miRNA pacjenta i porównania go z opracowanymi wcześniej profilami zmian miRNA powiązanymi z występowaniem danego rodzaju choroby nowotworowej. Informacja o zmianach profilu miRNA podstawowych w regulacji ekspresji genów związanych z procesami nowotworzenia, mogłaby się przyczynić do opracowania terapii eksperymentalnych opartych na przywróceniu pierwotnego poziomu miRNA w komórkach, a tym samym, na przywróceniu prawidłowej regulacji ekspresji genów. Coraz nowsze metody wyciszania i włączania ekspresji miRNA mogą w przyszłości zaowocować skutecznymi rozwiązaniami terapeutycznymi.
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Affiliation(s)
- Patrycja Paciorek
- Katedra Biofizyki Molekularnej, Wydział Biologii i Ochrony Środowiska , Uniwersytet Łódzki
| | - Mariusz Żuberek
- Katedra Biofizyki Molekularnej, Wydział Biologii i Ochrony Środowiska , Uniwersytet Łódzki
| | - Agnieszka Grzelak
- Katedra Biofizyki Molekularnej, Wydział Biologii i Ochrony Środowiska , Uniwersytet Łódzki
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16
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Poel D, Gootjes EC, Bakkerus L, Trypsteen W, Dekker H, van der Vliet HJ, van Grieken NCT, Verhoef C, Buffart TE, Verheul HMW. A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer. Cancer Med 2020; 9:7558-7571. [PMID: 32864858 PMCID: PMC7571833 DOI: 10.1002/cam4.3371] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/24/2022] Open
Abstract
Background Palliative systemic therapy is currently standard of care for patients with extensive metastatic colorectal cancer (mCRC). A biomarker predicting chemotherapy benefit which prevents toxicity from ineffective treatment is urgently needed. Therefore, a previously developed tissue‐derived microRNA profile to predict clinical benefit from chemotherapy was evaluated in tissue biopsies and serum from patients with mCRC. Methods Samples were prospectively collected from patients (N = 132) who were treated with capecitabine or 5‐FU/LV with oxaliplatin ± bevacizumab. Response evaluation was performed according to RECIST 1.1 after three or four cycles, respectively. Baseline tissue and serum miRNAs expression levels of miR‐17‐5p, miR‐20a‐5p, miR‐30a‐5p, miR‐92a‐3p, miR‐92b‐3p, and miR‐98‐5p were quantified with RT‐qPCR and droplet digital PCR, respectively. Combined predictive performance of selected variables was tested using logistic regression analysis. Results From 132 patients, 81 fresh frozen tissue biopsies from metastases and 93 serum samples were available. Based on expression levels of miRNAs in tissue, progressive disease could be predicted with an AUC of 0.85 (95% CI:0.72‐0.91) and response could be predicted with an AUC of 0.70 (95% CI:0.56‐0.80). This did not outperform clinical parameters alone (respectively P = .14 and P = .27). Expression levels of miR‐92a‐3p and miR‐98‐5p in serum significantly improved the predictive value of clinical parameters for response to chemotherapy (AUC 0.74, 95% CI:0.64‐0.84, P = .003) in this cohort. Conclusions The additive predictive value to clinical parameters of the tissue‐derived six miRNA profile for clinical benefit could not be validated in patients with mCRC treated with first‐line systemic therapy. Although miR‐92a‐3p and miR‐98‐5p serum levels improved the predictive value of clinical parameters, it remained insufficient for clinical decision‐making.
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Affiliation(s)
- Dennis Poel
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands.,Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Elske C Gootjes
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands.,Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Lotte Bakkerus
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands.,Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Wim Trypsteen
- Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, HIV Cure Research Center, Ghent University and Ghent University Hospital, Ghent, Belgium
| | - Henk Dekker
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands
| | - Hans J van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands
| | - Cornelis Verhoef
- Division of Surgical Oncology, Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Tineke E Buffart
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands.,Department of Gastrointestinal Oncology, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Henk M W Verheul
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU Universiteit Medical Center Amsterdam, Amsterdam, the Netherlands.,Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
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17
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Gonzalez-Villarreal CA, Quiroz-Reyes AG, Islas JF, Garza-Treviño EN. Colorectal Cancer Stem Cells in the Progression to Liver Metastasis. Front Oncol 2020; 10:1511. [PMID: 32974184 PMCID: PMC7468493 DOI: 10.3389/fonc.2020.01511] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 07/14/2020] [Indexed: 12/12/2022] Open
Abstract
Colorectal carcinoma (CRC) is a leading cause of cancer mortality. Tumorigenesis is a dynamic process wherein cancer stem cells (CSCs) and their microenvironment promote initiation, progression, and metastasis. Metastatic colonization is an inefficient process that is very complex and is poorly understood; however, in most cases, metastatic disease is not curable, and resistance mechanisms tend to develop against conventional treatments. An understanding of the underlying mechanisms and factors that contribute to the development of metastasis in CRC can aid in the search for specific therapeutic targets for improving standard treatments. In this review, we summarize current knowledge regarding tumor biology and the use of stroma cells as prognostic factors and inflammatory inducers associated with the use of tumor microenvironments as a promoter of cancer metastasis. Moreover, we look into the importance of CSC, pericytes, and circulating tumor cells as mechanisms that lead to liver metastasis, and we also focus on the cellular and molecular pathways that modulate and regulate epithelial–mesenchymal transition. Finally, we discuss a novel therapeutic target that can potentially eliminate CSCs as a CRC treatment.
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Affiliation(s)
| | - Adriana G Quiroz-Reyes
- Universidad Autonoma de Nuevo Leon Facultad de Medicina, Departamento de Bioquimica y Medicina Molecular, San Nicolás de los Garza, Mexico
| | - Jose F Islas
- Universidad Autonoma de Nuevo Leon Facultad de Medicina, Departamento de Bioquimica y Medicina Molecular, San Nicolás de los Garza, Mexico
| | - Elsa N Garza-Treviño
- Universidad Autonoma de Nuevo Leon Facultad de Medicina, Departamento de Bioquimica y Medicina Molecular, San Nicolás de los Garza, Mexico
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18
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Li M, Shan W, Hong B, Zou J, Li H, Han D, Zhang Y, Li L, Li D, Lin W. Circulating miR-92b and miR-375 for monitoring the chemoresistance and prognosis of small cell lung cancer. Sci Rep 2020; 10:12705. [PMID: 32728103 PMCID: PMC7391689 DOI: 10.1038/s41598-020-69615-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 07/12/2020] [Indexed: 01/13/2023] Open
Abstract
miRNAs have been reported to be stably detectable in plasma and to function as potent biomarkers in multiple cancers. The study aimed to evaluate the expression of candidate circulating miRNAs in patients with small cell lung cancer (SCLC) to identify potential noninvasive biomarkers. The expression of five miRNAs (miR-92b, miR-146a, miR-375, miR-1224, and miR-1246) was significantly upregulated in plasma after chemoresistance induction. Receiver operating characteristic curve (ROC) analysis showed that the area under the curve (AUC) values of miR-92b and miR-375 were 0.766 and 0.791, respectively. The data demonstrated that among the five miRNAs assessed, these two miRNAs had better diagnostic accuracy for monitoring drug resistance. In addition, miR-92b and miR-375 levels were decreased after effective chemotherapy. Furthermore, Kaplan–Meier survival analysis confirmed that high expression of miR-92b and miR-375 was closely related to shorter progression-free survival (PFS) in SCLC patients. In conclusion, these findings indicate that circulating miR-92b and miR-375 might be ideal noninvasive biomarkers for monitoring drug resistance during chemotherapy and evaluating the prognosis of patients with SCLC.
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Affiliation(s)
- Ming Li
- High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China.,University of Science and Technology of China, Hefei, 230036, China.,Division of Life Sciences and Medicine, Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230031, China
| | - Wulin Shan
- Division of Life Sciences and Medicine, Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230031, China
| | - Bo Hong
- High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China.,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China
| | - Jinglu Zou
- High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China.,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China
| | - Hong Li
- High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China.,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China
| | - Dandan Han
- Division of Life Sciences and Medicine, Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230031, China
| | - Yang Zhang
- Division of Life Sciences and Medicine, Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230031, China
| | - Lailing Li
- Division of Life Sciences and Medicine, Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230031, China
| | - Dan Li
- Division of Life Sciences and Medicine, Department of Laboratory Diagnostics, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230031, China
| | - Wenchu Lin
- High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China. .,Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
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19
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Wang W, Xie Y, Chen F, Liu X, Zhong LL, Wang HQ, Li QC. LncRNA MEG3 acts a biomarker and regulates cell functions by targeting ADAR1 in colorectal cancer. World J Gastroenterol 2019; 25:3972-3984. [PMID: 31413531 PMCID: PMC6689807 DOI: 10.3748/wjg.v25.i29.3972] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 06/07/2019] [Accepted: 06/26/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most prevalent malignancy and has the fourth highest global cancer mortality rate. Early diagnosis and prompt medical attention can improve quality of life and the prognosis of CRC patients. Accumulating evidence reveals that long non-coding RNAs (lncRNAs) function as oncogenes or anti-oncogenes, as well as biomarkers in various cancers.
AIM To investigate the levels and molecular mechanism of the lncRNA maternally expressed gene 3 (MEG3) in CRC.
METHODS The levels of lncRNA MEG3 in CRC tissue, serum and cell line samples were explored via qRT-PCR. The relationship between MEG3 levels and clinicopathological features in CRC was investigated. The diagnostic and prognostic values of serum MEG3 levels were analyzed with ROC curves and Kaplan‑Meier survival curves, respectively.
RESULTS Significant decreased levels of MEG3 existed in CRC tissue, cell lines and serum. CRC patients with down-regulated serum MEG3 levels had larger tumor sizes, and advanced clinical stages. The sensitivity and specificity of serum MEG3 levels in CRC detection was 0.667 and 0.875, respectively. Tumor size, T stages, and serum MEG3 levels are indie factors that produce an effect on CRC patients' prognosis. Kaplan‑Meier survival curves suggested that CRC patients with high levels of MEG3 had a remarkably better overall survival rate.
CONCLUSION LncRNA MEG3 is down-regulated in CRC, and regulates cell functions by targeting adenosine deaminase’s effect on RNA 1 in CRC.
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Affiliation(s)
- Wei Wang
- College of Basic Medical Sciences, China medical University and Department of Pathology, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Teaching and Research Department of Pathology, Basic Medical College, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Ying Xie
- Department of Synopsis of The Golden Chamber, School of Basic Medical Sciences, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Fei Chen
- Department of Synopsis of The Golden Chamber, School of Basic Medical Sciences, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Xu Liu
- Experiment and Training Center, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Li-Li Zhong
- Department of Pathology, the First Clinical Medical College, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Hai-Qiang Wang
- Department of Gastroenterology, the First Clinical Medical College, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Qing-Chang Li
- College of Basic Medical Sciences, China medical University and Department of Pathology, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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20
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Barchitta M, Maugeri A, Li Destri G, Basile G, Agodi A. Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies. Int J Mol Sci 2019; 20:ijms20153842. [PMID: 31390840 PMCID: PMC6696286 DOI: 10.3390/ijms20153842] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 07/30/2019] [Accepted: 08/02/2019] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) represents the third-most common cancer worldwide and one of the main challenges for public health. Despite great strides in the application of neoadjuvant and adjuvant therapies for rectal and colon cancer patients, each of these treatments is still associated with certain adverse effects and different response rates. Thus, there is an urgent need for identifying novel potential biomarkers that might guide personalized treatments for specific subgroups of patients. However, until now, there are no biomarkers to predict the manifestation of adverse effects and the response to treatment in CRC patients. Herein, we provide a systematic review of epidemiological studies investigating epigenetic biomarkers in CRC patients receiving neoadjuvant or adjuvant therapy, and their potential role for the prediction of outcomes and response to treatment. With this aim in mind, we identified several epigenetic markers in CRC patients who received surgery with adjuvant or neoadjuvant therapy. However, none of them currently has the robustness to be translated into the clinical setting. Thus, more efforts and further large-size prospective studies and/or trials should be encouraged to develop epigenetic biomarker panels for personalized prevention and medicine in CRC cancer.
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Affiliation(s)
- Martina Barchitta
- Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, via S. Sofia, 87, 95123 Catania, Italy
| | - Andrea Maugeri
- Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, via S. Sofia, 87, 95123 Catania, Italy
| | - Giovanni Li Destri
- Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, via S. Sofia, 87, 95123 Catania, Italy
| | - Guido Basile
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, via S. Sofia, 78, 95123 Catania, Italy
| | - Antonella Agodi
- Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, via S. Sofia, 87, 95123 Catania, Italy.
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Peng Q, Feng Z, Shen Y, Zhu J, Zou L, Shen Y, Zhu Y. Integrated analyses of microRNA-29 family and the related combination biomarkers demonstrate their widespread influence on risk, recurrence, metastasis and survival outcome in colorectal cancer. Cancer Cell Int 2019; 19:181. [PMID: 31346316 PMCID: PMC6633652 DOI: 10.1186/s12935-019-0907-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 07/10/2019] [Indexed: 12/24/2022] Open
Abstract
Background Emerging evidence has revealed miR-29 family as promising biomarkers for colorectal cancer (CRC), but their biomarker potential and molecular mechanisms remain poorly understood. Methods We performed a comprehensive meta-analysis to evaluate the biomarker performance of individual miR-29 and the related miRNA combination biomarkers. Meanwhile, we conducted an integrative bioinformatics analysis to unfold the underlying biological function of miR-29 and their relationship with CRC. Results Using miR-29 expression to diagnose CRC produced 0.82 area under the curve, 70% sensitivity and 81% specificity while the combination biomarkers based on miR-29 enhanced the diagnostic power with an AUC of 0.86, a sensitivity of 78% and a specificity of 91%. For the prognosis evaluation, patients with higher expression of miR-29 had better survival outcome (pooled HR 0.78; 95% CI 0.56–1.07). In addition, miR-29 has also been identified as potential biomarker for predicting recurrence and metastasis in CRC. Then the genes regulated by the miR-29 family were retrieved and found closely associated with the molecular pathogenesis of CRC according to the gene ontology and pathway analysis. Furthermore, hub nodes and significant modules were identified from the protein–protein interaction network constructed with miR-29 family targets, which were also confirmed highly involved in the establishment and development of CRC. Conclusions Current evidences suggest miR-29 family may become promising biomarkers for risk, recurrence, metastasis and survival outcome of CRC. Meanwhile our data highlight the potential clinical use of miRNA combination biomarkers. Nevertheless, further prospective studies are warranted before the application of the useful biomarkers in the clinical.
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Affiliation(s)
- Qiliang Peng
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu 215004 China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Zhengyang Feng
- 3Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yi Shen
- 4Department of Radiation Oncology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou Science & Technology Town Hospital, Suzhou, China
| | - Jiahao Zhu
- Tongda College of Nanjing University of Post and Telecommunications, Yangzhou, China
| | - Li Zou
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu 215004 China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yuntian Shen
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu 215004 China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yaqun Zhu
- 1Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu 215004 China.,2Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
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22
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Dehghan F, Boozarpour S, Torabizadeh Z, Alijanpour S. miR-21: a promising biomarker for the early detection of colon cancer. Onco Targets Ther 2019; 12:5601-5607. [PMID: 31371997 PMCID: PMC6628966 DOI: 10.2147/ott.s199508] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 05/18/2019] [Indexed: 12/24/2022] Open
Abstract
Purpose The aim of this study was to compare the expression of miR-21 gene in stages II-IV of formalin-fixed paraffin-embedded (FFPE) tissue in patients with colon cancer and introduce miR-21 as a potential molecular marker for detection of colon cancer in the early stages. Introduction Currently, identification of key molecules involved in the pathogenesis of cancer is one of the areas under consideration. miRNAs, are small RNAs which have been identified in many cancers. In this study, we investigated the expression of miR-21 in three pathologic stages in patients with colon cancer in the north of Iran. Patients and methods A total of 40 FFPE samples were obtained from patients with stages II, III, and IV from hospitals in Mazandaran and Golestan provinces. After extraction of RNA, treatment with DNase I and cDNA synthesis was performed and miR-21 expression was assessed by qPCR. Then, the data were analyzed using statistical software R (3.4.3). Results The expression of miR-21 in stage II was significantly different from stage IV. However, no significant difference was observed between the other stages. In stage II, the level of miR-21 expression was higher in men than women. Moreover, in the second pathological stage, miR-21 expression was reduced in patients with adjacent lymphoid tissue engagement. In addition, the expression of miR-21 in grade I was significantly higher than grade II. Conclusion The results of this study suggest that miR-21 can be a diagnostic marker for early stages of colon cancer, especially in men. It can also be considered as a good candidate for targeted treatment of colon cancer in the early stages of the disease. Furthermore, for the first time, we suggested that miR-21 can be a good molecular marker for classification of the stages of colon cancer.
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Affiliation(s)
- Farnaz Dehghan
- Department of Biology, Faculty of Basic Sciences, Gonbad kavous University, Gonbad kavous, Golestan, Iran
| | - Sohrab Boozarpour
- Department of Biology, Faculty of Basic Sciences, Gonbad kavous University, Gonbad kavous, Golestan, Iran
| | - Zhila Torabizadeh
- Department of Medical Pathology, Faculty of Medicine, Sari University of Medical Sciences, Sari, Mazandaran, Iran
| | - Sakineh Alijanpour
- Department of Biology, Faculty of Basic Sciences, Gonbad kavous University, Gonbad kavous, Golestan, Iran
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Peng Q, Shen Y, Lin K, Zou L, Shen Y, Zhu Y. Identification of microRNA-92a and the related combination biomarkers as promising substrates in predicting risk, recurrence and poor survival of colorectal cancer. J Cancer 2019; 10:3154-3171. [PMID: 31289586 PMCID: PMC6603388 DOI: 10.7150/jca.30306] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 04/28/2019] [Indexed: 12/15/2022] Open
Abstract
Background: Previous studies demonstrated that microRNA-92a (miR-92a) may serve as a novel promising biomarker in colorectal cancer (CRC) patients. However, a comprehensive analysis of the contribution of miR-92a in CRC is lacking. We aimed to systematically summarize the diagnostic and prognostic values of miR-92a in CRC. Methods: The diagnostic and prognostic roles of individual miR-92a and the combination biomarkers based on miR-92a were evaluated through comprehensive meta-analyses. Meanwhile, the function and potential mechanisms of miR-92a were assessed by an integrative bioinformatics analysis. Results: According to the results, we found that miR-92a yielded a pooled area under ROC curve (AUC) of 0.82 (sensitivity: 76%, specificity: 75%) in discriminating CRC from controls. Notably, the combination biomarkers based on miR-92a increased the diagnostic performance, yielding an AUC of 0.91, with a sensitivity of 83% and a specificity of 87%. For the prognostic meta-analysis, patients with higher expression of miR-92a had significant shorter overall survival (pooled HR: 2.30; 95% CI: 1.03-5.12). In addition, the regulated genes of miR-92a were retrieved and enriched through gene ontology and pathway analysis, indicating their correlations with the initiation and progression of CRC. Furthermore, protein-protein interaction network was set up with miR-92a targets and screened for hub nodes and significant modules, which were confirmed strongly involved in the occurrence and development of CRC again. Conclusions: Current evidences suggest miR-92a is a promising biomarker for early detection and prognosis of CRC while miRNA combination biomarkers may be considered as the right way for clinical practice. However, more prospective studies are required to highlight the theoretical strengths.
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Affiliation(s)
- Qiliang Peng
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yi Shen
- Department of Radiation Oncology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou Science & Technology Town Hospital, Suzhou, China
| | - Kaisu Lin
- Department of Oncology, Nantong Rich Hospital, Nantong, China
| | - Li Zou
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yuntian Shen
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yaqun Zhu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
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Varkaris A, Katsiampoura A, Davis JS, Shah N, Lam M, Frias RL, Ivan C, Shimizu M, Morris J, Menter D, Overman M, Tran H, Heymach J, Chun YS, Vauthey JN, Calin G, Kopetz S. Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer. Br J Cancer 2019; 120:340-345. [PMID: 30636774 PMCID: PMC6353894 DOI: 10.1038/s41416-018-0360-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 10/03/2018] [Accepted: 11/27/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Metastatic colorectal cancer (mCRC) is a highly heterogeneous disease from a clinical, molecular, and immunological perspective. Current predictive models rely primarily in tissue based genetic analysis, which not always correlate with inflammatory response. Here we evaluated the role of a circulating inflammatory signature as a prognostic marker in mCRC. METHODS Two hundred eleven newly diagnosed patients with mCRC were enrolled in the study. One hundred twenty-one patients had unresectable metastases, whereas ninety patients had potentially resectable liver metastases at presentation. Analysis of miR-21, IL-6, and IL-8 in the plasma of peripheral blood was performed at baseline. Patients with high circulating levels of ≥2 of the three inflammation markers (miR-21, IL-6, and IL-8) were considered to have the "Inflammation phenotype-positive CISIG". RESULTS Positive CISIG was found in 39/90 (43%) and 50/121 (45%) patients in the resectable and unresectable cohort, respectively. In the resectable population the median relapse-free survival was 18.4 compared to 31.4 months (p = 0.001 HR 2.09, 95% CI 1.2-3.67) for positive vs. negative CISIG. In contrast, the individual components were not significant. In the same population the median overall survival was 46.2 compared to 66.0 months (p = 0.0003, HR 2.57, 95% CI 1.26-5.27) for positive vs. negative CISIG, but not significant for the individual components. In the unresectable population, the median overall survival was 13.5 compared to 25.0 months (p = 0.0008, HR 2.49, 95% CI 1.46-4.22) for positive vs. negative CISIG. IL-6 was independently prognostic with overall survival of 16.2 compared to 27.0 months (p = 0.004, HR 1.96, 95% CI 1.24-3.11) for high vs. low IL-6, but not the other components. Using a Cox regression model, we demonstrated that CISIG is an independent predictive marker of survival in patients with unresectable disease (HR 1.8, 95% CI 1.2, 2.8, p < 0.01). CONCLUSION In two different cohorts, we demonstrated that CISIG is a strong prognostic factor of relapse-free and overall survival of patients with mCRC. Based on these data, analysis of circulating inflammatory signaling can be complimentary to traditional molecular testing.
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Affiliation(s)
- Andreas Varkaris
- Department of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Anastasia Katsiampoura
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- St. Elizabeth's Medical Center, Boston, MA, USA
| | - Jennifer S Davis
- Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Neeraj Shah
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael Lam
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rosa Lizeth Frias
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cristina Ivan
- Department of Experimental Therapeutics, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Masayoshi Shimizu
- Department of Experimental Therapeutics, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey Morris
- Department of Biostatistics, Division of Science, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - David Menter
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael Overman
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hai Tran
- Department of Thoracic/Head and Neck Medical Oncology - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - John Heymach
- Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yun Shin Chun
- Hepato-Pancreato-Biliary Section, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Hepato-Pancreato-Biliary Section, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - George Calin
- Department of Experimental Therapeutics, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Yuan HL, Wang T, Zhang KH. MicroRNAs as potential biomarkers for diagnosis, therapy and prognosis of gastric cancer. Onco Targets Ther 2018; 11:3891-3900. [PMID: 30013369 PMCID: PMC6039071 DOI: 10.2147/ott.s156921] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Despite the widespread use of endoscopy and conventional tumor biomarkers, gastric cancer (GC) remains one of the most frequent causes of cancer-related deaths worldwide due to its late diagnosis and poor response to treatment. Valuable and practical biomarkers are urgently needed to screen patients with a high risk of GC that can complement endoscopic diagnosis. Such biomarkers will enable the efficient prediction of therapeutic response and prognosis of GC patients and favor the establishment of an effective treatment strategy for each and every patient. MicroRNAs (miRNAs) are a class of small non-coding RNA sequences that play important roles in modulating key biological processes by regulating the expression of target genes. Expectedly, miRNAs are abnormally expressed within the tumor tissue and in associated biological fluids of GC patients including their blood, gastric juice, and urine. Accumulating evidence indicates that miRNAs are potential biomarkers with multiple diagnostic functions for GC. Here, we review recent advances and challenges in using miRNAs, particularly biofluid miRNAs, as GC biomarkers with potential clinical applications including diagnosing, clinically staging, and predicting malignant behaviors, therapy response, recurrence after surgery and survival time.
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Affiliation(s)
- Hai-Liang Yuan
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, People's Republic of China,
| | - Ting Wang
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, People's Republic of China,
| | - Kun-He Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, People's Republic of China,
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26
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MiR-92a Inhibits the Progress of Osteosarcoma Cells and Increases the Cisplatin Sensitivity by Targeting Notch1. BIOMED RESEARCH INTERNATIONAL 2018; 2018:9870693. [PMID: 29984257 PMCID: PMC6011149 DOI: 10.1155/2018/9870693] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Accepted: 02/20/2018] [Indexed: 12/17/2022]
Abstract
Background MicroRNAs (miRs) have been implicated in the development and progression of osteosarcoma. Here, we aimed to illustrate the important role of miR-92a on the regulation of OS development which may help to establish a novel strategy for OS diagnosis and treatment. Materials and Methods Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were assessed by flow cytometry with PI and PI/Annexin-V stain, respectively. The expression of proteins was examined by western blot. qPCR was used to detect the expression of RNA. Cell migration was assayed with transwell assay. Results MiR-92a inhibited the proliferation and the migration of OS in vitro and reduced the volume of the tumour in vivo. Further, miR-92a enhanced cisplatin sensitivity of OS. MiR-92a directly targeted Notch1. Conclusion Together, our results indicate that miR-92a inhibited cell growth, migration, and enhanced cisplatin sensitivity of OS cell by targeting Notch1.
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27
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Li H, Wu Q, Li T, Liu C, Xue L, Ding J, Shi Y, Fan D. The miR-17-92 cluster as a potential biomarker for the early diagnosis of gastric cancer: evidence and literature review. Oncotarget 2018; 8:45060-45071. [PMID: 28178677 PMCID: PMC5542167 DOI: 10.18632/oncotarget.15023] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 01/19/2017] [Indexed: 12/20/2022] Open
Abstract
Purpose Intestinal metaplasia is considered to be a pre-cancerous lesion of gastric cancer. The miR-17-92 cluster was previously reported to have clinical value in the prediction of cancer development. This study aimed to test the diagnostic value of miR-17-92 in gastric cancer and the intestinal metaplasia patients compared with the normal ones. Results The results showed that miR-17-92 members were over-expressed in the serum of both gastric cancer and intestinal metaplasia patients, compared with healthy controls. Serum miR-17-92 members could also distinguish patients with gastric cancer and intestinal metaplasia from healthy controls. Materials and Methods Serum miR-17-92 expression levels were detected using quantitative real-time PCR in 75 patients with gastric cancer, 104 patients with intestinal metaplasia and 38 healthy controls. The Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were then analyzed to test the efficacy of the miR-17-92 members in distinguishing gastric cancer, intestinal metaplasia and healthy controls. Conclusions In conclusion, the miR-17-92 cluster might be useful as a potential serum biomarker for the early detection of gastric cancer.
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Affiliation(s)
- Hong Li
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Qiong Wu
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Ting Li
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Changhao Liu
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Lin Xue
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Jie Ding
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Yongquan Shi
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
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28
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Wilczyński M, Żytko E, Danielska J, Szymańska B, Dzieniecka M, Nowak M, Malinowski J, Owczarek D, Wilczyński JR. Clinical significance of miRNA-21, -103, -129, -150 in serous ovarian cancer. Arch Gynecol Obstet 2018; 297:741-748. [DOI: 10.1007/s00404-018-4660-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 01/09/2018] [Indexed: 02/07/2023]
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29
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Zhong W, Chen S, Qin Y, Zhang H, Wang H, Meng J, Huai L, Zhang Q, Yin T, Lei Y, Han J, He L, Sun B, Liu H, Liu Y, Zhou H, Sun T, Yang C. Doxycycline inhibits breast cancer EMT and metastasis through PAR-1/NF-κB/miR-17/E-cadherin pathway. Oncotarget 2017; 8:104855-104866. [PMID: 29285218 PMCID: PMC5739605 DOI: 10.18632/oncotarget.20418] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 06/27/2017] [Indexed: 01/12/2023] Open
Abstract
Doxycycline displays high efficiency for cancer therapy. However, the molecular mechanism is poorly understood. In our previous study, doxycycline was found to suppress tumor progression by directly targeting proteinase-activated receptor 1 (PAR1). In this study, microRNAs were found to be involved in PAR1-mediated anti-tumor effects of doxycycline. Among these miRNAs, miR-17 was found to promote breast cancer cell metastasis both in vivo and in vitro. Moreover, miR-17 could reverse partial doxycycline inhibition effects on breast cancer. Employing luciferase and chromatin immunoprecipitation assays, nuclear factor-kappaB (NF-κB) was found to bind miR-17 promoters. Furthermore, E-cadherin was identified as the target gene of miR-17. These results showed that miR-17 can resist the inhibitory effects of doxycycline on breast cancer epithelial–mesenchymal transformation (EMT) by targeting E-cadherin.
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Affiliation(s)
- Weilong Zhong
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Shuang Chen
- Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China
| | - Yuan Qin
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Heng Zhang
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Hongzhi Wang
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Jing Meng
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Longcong Huai
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Qiang Zhang
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Tingting Yin
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Yueyang Lei
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Jingxia Han
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Lingfei He
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China
| | - Bo Sun
- Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China
| | - Huijuan Liu
- Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China
| | - Yanrong Liu
- Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China
| | - Honggang Zhou
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China.,Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China
| | - Tao Sun
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China.,Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China
| | - Cheng Yang
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China.,Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China
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30
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Ivanov K, Donev I. International scientific communications in the field of colorectal tumour markers. World J Gastrointest Surg 2017; 9:127-138. [PMID: 28603585 PMCID: PMC5442406 DOI: 10.4240/wjgs.v9.i5.127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 11/16/2016] [Accepted: 03/22/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze scientometrically the dynamic science internationalization on colorectal tumour markers as reflected in five information portals and to outline the significant journals, scientists and institutions.
METHODS A retrospective problem-oriented search was performed in Web of Science Core Collection (WoS), MEDLINE, BIOSIS Citation Index (BIOSIS) and Scopus for 1986-2015 as well as in Dervent Innovations Index (Derwent) for 1995-2015. Several specific scientometric parameters of the publication output and citation activity were comparatively analyzed. The following scientometric parameters were analyzed: (1) annual dynamics of publications; (2) scientific institutions; (3) journals; (4) authors; (5) scientific forums; (6) patents - number of patents, names and countries of inventors, and (7) citations (number of citations to publications by single authors received in WoS, BIOSIS Citation Index and Scopus).
RESULTS There is a trend towards increasing publication output on colorectal tumour markers worldwide along with high citation rates. Authors from 70 countries have published their research results in journals and conference proceedings in 21 languages. There is considerable country stratification similar to that in most systematic investigations. The information provided to end users and scientometricians varies between these data-bases in terms of most parameters due to different journal coverage, indexing systems and editorial policy. The lists of the so-called “core” journals and most productive authors in WoS, BIOSIS, MEDLINE and Scopus along with the list of the most productive authors - inventors in Derwent present a particular interest to the beginners in the field, the institutional and national science managers and the journal editorial board members. The role of the purposeful assessment of scientific forums and patents is emphasized.
CONCLUSION Our results along with this problem-oriented collection containing the researchers’ names, addresses and publications could contribute to a more effective international collaboration of the coloproctologists from smaller countries and thus improve their visibility on the world information market.
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31
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Yang F, Li Y, Xu L, Zhu Y, Gao H, Zhen L, Fang L. miR-17 as a diagnostic biomarker regulates cell proliferation in breast cancer. Onco Targets Ther 2017; 10:543-550. [PMID: 28203087 PMCID: PMC5293507 DOI: 10.2147/ott.s127723] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background MicroRNAs (miRNAs) have been shown to be involved in the initiation and progression of cancers in the literature. In this study, we aimed to evaluate the clinicopathological role of miR-17 in breast cancer. Materials and methods The expression of miR-17 was measured in 132 breast cancer tissues and paired adjacent normal tissues by using real-time quantitative polymerase chain reaction. The association between miR-17 expression levels and clinicopathological parameters was also analyzed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays were used to investigate the role of miR-17 in the regulation of breast cancer cells. Results The expression of miR-17 was remarkably increased in breast cancer tissues and cell lines. Clinical association analysis revealed that a high expression of miR-17 was prominently associated with poor survival time in breast cancer. Overexpression of miR-17 promoted cell proliferation and induced tumor growth. Conclusion Our findings clarified that the upregulation of miR-17 played a vital role in breast cancer progression and suggested that miR-17 could be used as a prognostic biomarker for breast cancer.
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Affiliation(s)
- Fangliang Yang
- Department of Thyroid and Breast Surgery, Changzhou No 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou; Department of Thyroid and Breast Surgery, Shanghai No 10 People's Hospital, Clinical College of Nanjing Medical University, Shanghai, People's Republic of China
| | - Yuan Li
- Department of Thyroid and Breast Surgery, Changzhou No 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou
| | - Lingyun Xu
- Department of Thyroid and Breast Surgery, Changzhou No 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou
| | - Yulan Zhu
- Department of Thyroid and Breast Surgery, Changzhou No 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou
| | - Haiyan Gao
- Department of Thyroid and Breast Surgery, Changzhou No 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou
| | - Lin Zhen
- Department of Thyroid and Breast Surgery, Changzhou No 2 People's Hospital Affiliated to Nanjing Medical University, Changzhou
| | - Lin Fang
- Department of Thyroid and Breast Surgery, Shanghai No 10 People's Hospital, Clinical College of Nanjing Medical University, Shanghai, People's Republic of China
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32
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MiR-376a promotion of proliferation and metastases in ovarian cancer: Potential role as a biomarker. Life Sci 2016; 173:62-67. [PMID: 27979415 DOI: 10.1016/j.lfs.2016.12.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 12/09/2016] [Accepted: 12/11/2016] [Indexed: 12/15/2022]
Abstract
AIMS Ovarian cancer is the fifth most deadly cancer in women, and is usually diagnosed too late. Exploring specific and sensitive biomarkers will be helpful to early detection and will improve the survival rates of ovarian cancer patients. MAIN METHODS Realtime PCR was used to detect the expression of miR-376a. Wound healing and transwell assays were used to examined the migration and invasion abilities of ovarian cancer cells. Tumor xenograft experiments were employed to test the in vivo malignancy of ovarian cancer cells. Western Blotting and luciferase report assays were conducted for the target genes analysis. KEY FINDINGS Using a cohort of 32 cases of ovarian cancer and 10 cases of healthy control samples, we found that miR-376 expression is increased in ovarian cancer tissues. The serum level of miR-376a is significantly higher in ovarian cancer patients and is associated with the clinical stages of ovarian cancer. Over expression of miR-376a stimulated the proliferation, migration, and invasion of ovarian cancer cells, while inhibition of miR-376a expression blocked the proliferation, migration, and invasion. Data from nude mice further demonstrated the stimulatory role of miR-376a in ovarian cancer progression. Mechanically, miR-376a played its role by targeting KLF15 and Caspase-8. SIGNIFICANCE Our findings enrich the knowledge of miR-376a in ovarian cancer formation and progression, providing a possibility of using miR-376a as a diagnostic and prognostic biomarker for ovarian cancer.
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33
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Su K, Zhang T, Wang Y, Hao G. Diagnostic and prognostic value of plasma microRNA-195 in patients with non-small cell lung cancer. World J Surg Oncol 2016; 14:224. [PMID: 27733164 PMCID: PMC5062829 DOI: 10.1186/s12957-016-0980-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 08/13/2016] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Recently, circulating microRNAs (miRNAs) have been reported to be stably detectable in plasma/serum and to function as potent biomarkers in various cancers. The aim of this study was to evaluate the expression level of plasma miRNA-195 in patients with non-small cell lung cancer (NSCLC) and investigate its diagnostic and prognostic value. METHODS Quantitative real-time PCR was performed to evaluate plasma miRNA-195 levels in 100 NSCLC patients and 100 healthy volunteers. The association between miRNA-195 expression and clinicopathological factors as well as the overall survival was analyzed. Receiver-operating characteristic (ROC) curve analysis was carried out to assess the potential value of plasma miRNA-195 for NSCLC diagnosis. RESULTS Plasma miRNA-195 was downregulated in NSCLC patients compared with healthy controls (P < 0.001). Decreased plasma miRNA-195 expression was significantly associated with lymph node metastasis and advanced clinical stage. ROC curve analysis showed that plasma miRNA-195 was a useful marker for NSCLC diagnosis. Multivariate Cox regression analysis confirmed low plasma miRNA-195 expression as an independent unfavorable prognostic factor for NSCLC patients. CONCLUSIONS These findings indicate that plasma miRNA-195 might serve as a promising biomarker for the early detection and prognosis evaluation of NSCLC.
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Affiliation(s)
- Keli Su
- Department of Oncology, The Fourth People's Hospital of Jinan, NO. 50, Shifan Road, Jinan, 250031, Shandong Province, China
| | - Tingcui Zhang
- Department of Internal Medicine, The Central Hospital of Jinan, Jinan, 250012, Shandong Province, China
| | - Yongrui Wang
- Department of Clinical Laboratory, The Fourth People's Hospital of Jinan, Jinan, 250031, Shandong Province, China
| | - Guijun Hao
- Department of Oncology, The Fourth People's Hospital of Jinan, NO. 50, Shifan Road, Jinan, 250031, Shandong Province, China.
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34
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Larrea E, Sole C, Manterola L, Goicoechea I, Armesto M, Arestin M, Caffarel MM, Araujo AM, Araiz M, Fernandez-Mercado M, Lawrie CH. New Concepts in Cancer Biomarkers: Circulating miRNAs in Liquid Biopsies. Int J Mol Sci 2016; 17:ijms17050627. [PMID: 27128908 PMCID: PMC4881453 DOI: 10.3390/ijms17050627] [Citation(s) in RCA: 181] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Revised: 04/18/2016] [Accepted: 04/18/2016] [Indexed: 12/19/2022] Open
Abstract
The effective and efficient management of cancer patients relies upon early diagnosis and/or the monitoring of treatment, something that is often difficult to achieve using standard tissue biopsy techniques. Biological fluids such as blood hold great possibilities as a source of non-invasive cancer biomarkers that can act as surrogate markers to biopsy-based sampling. The non-invasive nature of these “liquid biopsies” ultimately means that cancer detection may be earlier and that the ability to monitor disease progression and/or treatment response represents a paradigm shift in the treatment of cancer patients. Below, we review one of the most promising classes of circulating cancer biomarkers: microRNAs (miRNAs). In particular, we will consider their history, the controversy surrounding their origin and biology, and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.
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Affiliation(s)
- Erika Larrea
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - Carla Sole
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - Lorea Manterola
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - Ibai Goicoechea
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María Armesto
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María Arestin
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María M Caffarel
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
- IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
| | - Angela M Araujo
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
| | - María Araiz
- Hematology Department, Donostia Hospital, 20014 San Sebastián, Spain.
| | | | - Charles H Lawrie
- Molecular Oncology, Biodonostia Research Institute, 20014 San Sebastián, Spain.
- IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
- Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK.
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