1
|
Luan L, Yang L, Zhang Y, Liu J, Hu B, Ye L, Ye W, Shen J, Chen H, Qu X, Yang H, Li Y. Highly Sensitive Multiplexed Sensing of miRNAs in a Gastric Cancer Patient's Liquid Biopsy. Anal Chem 2024; 96:20015-20025. [PMID: 39641615 DOI: 10.1021/acs.analchem.4c04639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. Most patients are in the advanced stage of the disease at the time of diagnosis because the symptoms of early gastric cancer patients are not obvious. Early diagnosis of gastric cancer is still challenging due to the high cost, invasiveness, and low accuracy of traditional diagnostic methods such as endoscopy and biopsy. Herein, we develop clinically accurate and highly sensitive detection of multiple GC miRNA biomarkers in human serum using an isothermal nucleic acid primer exchange reaction (PER). The isothermal nucleic acid primer exchange reaction demonstrates high sensitivity and robustness, exemplified by a one-pot reaction achieving a detection limit of 28.71 fM. By quantifying the levels of three miRNA biomarkers selected through bioinformatics analysis in gastric cancer serum samples, the diagnostic approach effectively distinguished between clinical gastric cancer patients (n = 25) and noncancer controls (n = 10). The performance of our three-miRNA signature in discriminating between GC and controls was as follows: area under the curve (AUC): 0.808, sensitivity: 89%, specificity: 88%, positive predictive value (PPV): 96%, and negative predictive value (NPV): 70%.
Collapse
Affiliation(s)
- Liang Luan
- Department of Laboratory Medical Center, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Lin Yang
- Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province and School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen 518107, China
| | - Yating Zhang
- Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province and School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen 518107, China
| | - Jing Liu
- Department of Laboratory Medical Center, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Bingtao Hu
- Department of Laboratory Medical Center, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Lingzhi Ye
- Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province and School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen 518107, China
| | - Wei Ye
- Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province and School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen 518107, China
| | - Jienan Shen
- Center for Bionic Sensing and Intelligence, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Hong Chen
- Pen-Tung Sah Institute of Micro-Nano Science and Technology, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen 361005, Fujian, China
| | - Xiangmeng Qu
- Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province and School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen 518107, China
| | - Hui Yang
- Center for Bionic Sensing and Intelligence, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Yunhui Li
- Department of Laboratory Medical Center, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang 110016, China
| |
Collapse
|
2
|
Kang J, Kim H, Lee Y, Lee H, Park Y, Jang H, Kim J, Lee M, Jeong B, Byun J, Kim SJ, Lim E, Jung J, Woo E, Kang T, Park K. Unveiling Cas12j Trans-Cleavage Activity for CRISPR Diagnostics: Application to miRNA Detection in Lung Cancer Diagnosis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2402580. [PMID: 39354694 PMCID: PMC11600238 DOI: 10.1002/advs.202402580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 07/25/2024] [Indexed: 10/03/2024]
Abstract
Cas12j, a hypercompact and efficient Cas protein, has potential for use in CRISPR diagnostics, but has not yet been used because the trans-cleavage activity of Cas12j is veiled. Here, the trans-cleavage behavior of Cas12j1, 2, and 3 variants and evaluate their suitability for nucleic acid detection is unveiled. The target preferences and mismatch specificities of the Cas12j variants are precisely investigated and the optimal Cas12j reaction conditions are determined. As a result, the EXP-J assay for miRNA detection by harnessing the robust trans-cleavage activity of Cas12j on short ssDNA is developed. The EXP-J method demonstrates exceptional detection capabilities for miRNAs, proving that Cas12j can be a pivotal component in molecular diagnostics. Furthermore, the translational potential of the EXP-J assay is validated by detecting oncogenic miRNAs in plasma samples from lung cancer patients. This investigation not only elucidates the trans-cleavage characteristics of Cas12j variants, but also advances the Cas12j-based diagnostic toolkit.
Collapse
Affiliation(s)
- Ju‐Eun Kang
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
- Department of Proteome Structural BiologyKRIBB School of BioscienceUniversity of Science and Technology (UST)Daejeon34113Republic of Korea
| | - Hansol Kim
- Bionanotechnology Research CenterKRIBBDaejeon34141Republic of Korea
| | - Young‐Hoon Lee
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
- Department of Proteome Structural BiologyKRIBB School of BioscienceUniversity of Science and Technology (UST)Daejeon34113Republic of Korea
| | - Ha‐Yeong Lee
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
| | - Yeonkyung Park
- Bionanotechnology Research CenterKRIBBDaejeon34141Republic of Korea
| | - Hyowon Jang
- Bionanotechnology Research CenterKRIBBDaejeon34141Republic of Korea
| | - Jae‐Rin Kim
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
- Department of Proteome Structural BiologyKRIBB School of BioscienceUniversity of Science and Technology (UST)Daejeon34113Republic of Korea
| | - Min‐Young Lee
- Department of Nano‐Bio Convergence, Surface Materials DivisionKorea Institute of Materials Science (KIMS)ChangwonGyeongsangnam‐do51508Republic of Korea
| | - Byeong‐Ho Jeong
- Division of Pulmonary and Critical Care MedicineDepartment of MedicineSamsung Medical CenterSungkyunkwan University (SKKU) School of MedicineSeoul06351Republic of Korea
| | - Ju‐Young Byun
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
- Bionanotechnology Research CenterKRIBBDaejeon34141Republic of Korea
| | - Seung Jun Kim
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
| | - Eun‐Kyung Lim
- Bionanotechnology Research CenterKRIBBDaejeon34141Republic of Korea
- School of PharmacySKKUSuwonGyeongi‐do16419Republic of Korea
- Department of NanobiotechnologyKRIBB School of Biotechnology, USTDaejeon34113Republic of Korea
| | - Juyeon Jung
- Bionanotechnology Research CenterKRIBBDaejeon34141Republic of Korea
- School of PharmacySKKUSuwonGyeongi‐do16419Republic of Korea
- Department of NanobiotechnologyKRIBB School of Biotechnology, USTDaejeon34113Republic of Korea
| | - Eui‐Jeon Woo
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
- Department of Proteome Structural BiologyKRIBB School of BioscienceUniversity of Science and Technology (UST)Daejeon34113Republic of Korea
- Disease Target Structure Research CenterKRIBBDaejeon34141Republic of Korea
| | - Taejoon Kang
- Bionanotechnology Research CenterKRIBBDaejeon34141Republic of Korea
- School of PharmacySKKUSuwonGyeongi‐do16419Republic of Korea
| | - Kwang‐Hyun Park
- Critical Diseases Diagnostics Convergence Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)Daejeon34141Republic of Korea
- Department of Proteome Structural BiologyKRIBB School of BioscienceUniversity of Science and Technology (UST)Daejeon34113Republic of Korea
- Disease Target Structure Research CenterKRIBBDaejeon34141Republic of Korea
| |
Collapse
|
3
|
Maqueda JJ, De Feo A, Scotlandi K. Evaluating Circulating Biomarkers for Diagnosis, Prognosis, and Tumor Monitoring in Pediatric Sarcomas: Recent Advances and Future Directions. Biomolecules 2024; 14:1306. [PMID: 39456239 PMCID: PMC11506719 DOI: 10.3390/biom14101306] [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: 08/30/2024] [Revised: 10/10/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Pediatric sarcomas present a significant challenge in oncology. There is an urgent need for improved therapeutic strategies for high-risk patients and better management of long-term side effects for those who survive the disease. Liquid biopsy is emerging as a promising tool to optimize treatment in these patients by offering non-invasive, repeatable assessments of disease status. Circulating biomarkers can provide valuable insights into tumor genetics and treatment response, potentially facilitating early diagnosis and dynamic disease monitoring. This review examines the potential of liquid biopsies, focusing on circulating biomarkers in the most common pediatric sarcomas, i.e., osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma. We also highlight the current research efforts and the necessary advancements required before these technologies can be widely adopted in clinical practice.
Collapse
Affiliation(s)
- Joaquín J. Maqueda
- Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; (A.D.F.); (K.S.)
| | | | | |
Collapse
|
4
|
Ssedyabane F, Obuku EA, Namisango E, Ngonzi J, Castro CM, Lee H, Randall TC, Ocan M, Apunyo R, Annet Kinengyere A, Kajabwangu R, Tahirah Kisawe A, Nambi Najjuma J, Tusubira D, Niyonzima N. The diagnostic accuracy of serum and plasma microRNAs in detection of cervical intraepithelial neoplasia and cervical cancer: A systematic review and meta-analysis. Gynecol Oncol Rep 2024; 54:101424. [PMID: 38939506 PMCID: PMC11208915 DOI: 10.1016/j.gore.2024.101424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 05/10/2024] [Accepted: 05/19/2024] [Indexed: 06/29/2024] Open
Abstract
Studies suggest a need for new diagnostic approaches for cervical cancer including microRNA technology. In this review, we assessed the diagnostic accuracy of microRNAs in detecting cervical cancer and Cervical Intraepithelial Neoplasia (CIN). We performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline for protocols (PRISMA-P). We searched for all articles in online databases and grey literature from 01st January 2012 to 16th August 2022. We used the quality assessment of diagnostic accuracy studies tool (QUADAS-2) to assess the risk of bias of included studies and then conducted a Random Effects Meta-analysis. We identified 297 articles and eventually extracted data from 24 studies. Serum/plasma concentration miR-205, miR-21, miR-192, and miR-9 showed highest diagnostic accuracy (AUC of 0.750, 0.689, 0.980, and 0.900, respectively) for detecting CIN from healthy controls. MicroRNA panels (miR-21, miR-125b and miR-370) and (miR-9, miR-10a, miR-20a and miR-196a and miR-16-2) had AUC values of 0.897 and 0.886 respectively for detecting CIN from healthy controls. For detection of cervical cancer from healthy controls, the most promising microRNAs were miR-21, miR-205, miR-192 and miR-9 (AUC values of 0.723, 0.960, 1.00, and 0.99 respectively). We report higher diagnostic accuracy of upregulated microRNAs, especially miR-205, miR-9, miR-192, and miR-21. This highlights their potential as stand-alone screening or diagnostic tests, either with others, in a new algorithm, or together with other biomarkers for purposes of detecting cervical lesions. Future studies could standardize quantification methods, and also study microRNAs in higher prevalence populations like in sub-Saharan Africa and South Asia. Our review protocol was registered in PROSPERO (CRD42022313275).
Collapse
Affiliation(s)
- Frank Ssedyabane
- Department of Medical Laboratory Science, Faculty of Medicine, Mbarara University of Science of Science and Technology, P.O. Box 1410 Mbarara, Uganda
| | - Ekwaro A. Obuku
- Africa Centre for Systematic Reviews and Knowledge Translation, College of Health Sciences, Makerere University, P.O Box 7072, Upper Mulago Hill Road, Kampala, Uganda
- Clinical Epidemiology Unit, Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, P.O. Box 7072 Kampala, Uganda
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, University of London, London, UK
| | - Eve Namisango
- Africa Centre for Systematic Reviews and Knowledge Translation, College of Health Sciences, Makerere University, P.O Box 7072, Upper Mulago Hill Road, Kampala, Uganda
| | - Joseph Ngonzi
- Department of Obstetrics and Gynecology, Mbarara University of Science of Science and Technology, P.O. Box 1410 Mbarara Uganda
| | - Cesar M. Castro
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Hakho Lee
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Thomas C. Randall
- Department of Global Health and Social Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Moses Ocan
- Africa Centre for Systematic Reviews and Knowledge Translation, College of Health Sciences, Makerere University, P.O Box 7072, Upper Mulago Hill Road, Kampala, Uganda
- Department of Pharmacology & Therapeutics, Makerere University, P.O. Box 7072 Kampala, Uganda
| | - Robert Apunyo
- Africa Centre for Systematic Reviews and Knowledge Translation, College of Health Sciences, Makerere University, P.O Box 7072, Upper Mulago Hill Road, Kampala, Uganda
| | - Alison Annet Kinengyere
- Africa Centre for Systematic Reviews and Knowledge Translation, College of Health Sciences, Makerere University, P.O Box 7072, Upper Mulago Hill Road, Kampala, Uganda
- Sir Albert Cook Medical Library, College of Health Sciences, Makerere University P.O Box 7072, Upper Mulago Hill Road, Kampala, Uganda
| | - Rogers Kajabwangu
- Department of Obstetrics and Gynecology, Mbarara University of Science of Science and Technology, P.O. Box 1410 Mbarara Uganda
| | - Aziza Tahirah Kisawe
- Department of Medical Laboratory Science, Faculty of Medicine, Mbarara University of Science of Science and Technology, P.O. Box 1410 Mbarara, Uganda
| | - Josephine Nambi Najjuma
- Department of Nursing, Mbarara University of Science of Science and Technology, P.O. Box 1410 Mbarara Uganda
| | - Deusdedit Tusubira
- Department of Biochemistry, Mbarara University of Science of Science and Technology, P.O. Box 1410 Mbarara Uganda
| | - Nixon Niyonzima
- Research and Training Directorate, Uganda Cancer Institute, P. O. Box 3935 Kampala, Uganda
| |
Collapse
|
5
|
Kazemi MS, Shoari A, Salehibakhsh N, Aliabadi HAM, Abolhosseini M, Arab SS, Ahmadieh H, Kanavi MR, Behdani M. Anti-angiogenic biomolecules in neovascular age-related macular degeneration; therapeutics and drug delivery systems. Int J Pharm 2024; 659:124258. [PMID: 38782152 DOI: 10.1016/j.ijpharm.2024.124258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/10/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024]
Abstract
Blindness in the elderly is often caused by age-related macular degeneration (AMD). The advanced type of AMD known as neovascular AMD (nAMD) has been linked to being the predominant cause of visual impairment in these people. Multiple neovascular structures including choroidal neovascular (CNV) membranes, fluid exudation, hemorrhages, and subretinal fibrosis, are diagnostic of nAMD. These pathological alterations ultimately lead to anatomical and visual loss. It is known that vascular endothelial growth factor (VEGF), a type of proangiogenic factor, mediates the pathological process underlying nAMD. Therefore, various therapies have evolved to directly target the disease. In this review article, an attempt has been made to discuss general explanations about this disease, all common treatment methods based on anti-VEGF drugs, and the use of drug delivery systems in the treatment of AMD. Initially, the pathophysiology, angiogenesis, and different types of AMD were described. Then we described current treatments and future treatment prospects for AMD and outlined the advantages and disadvantages of each. In this context, we first examined the types of therapeutic biomolecules and anti-VEGF drugs that are used in the treatment of AMD. These biomolecules include aptamers, monoclonal antibodies, small interfering RNAs, microRNAs, peptides, fusion proteins, nanobodies, and other therapeutic biomolecules. Finally, we described drug delivery systems based on liposomes, nanomicelles, nanoemulsions, nanoparticles, cyclodextrin, dendrimers, and composite vehicles that are used in AMD therapy.
Collapse
Affiliation(s)
- Mir Salar Kazemi
- Biotechnology Research Centre, Venom and Biotherapeutics Molecules Laboratory, Pasteur Institute of Iran, Iran
| | - Alireza Shoari
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
| | - Neda Salehibakhsh
- Biotechnology Research Centre, Venom and Biotherapeutics Molecules Laboratory, Pasteur Institute of Iran, Iran; Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Hooman Aghamirza Moghim Aliabadi
- Protein Chemistry Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Mohammad Abolhosseini
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Shahriar Arab
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hamid Ahmadieh
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mozhgan Rezaei Kanavi
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mahdi Behdani
- Biotechnology Research Centre, Venom and Biotherapeutics Molecules Laboratory, Pasteur Institute of Iran, Iran.
| |
Collapse
|
6
|
Kunysz M, Cieśla M, Darmochwał-Kolarz D. Evaluation of miRNA Expression in Patients with Gestational Diabetes Mellitus: Investigating Diagnostic Potential and Clinical Implications. Diabetes Metab Syndr Obes 2024; 17:881-891. [PMID: 38414865 PMCID: PMC10898488 DOI: 10.2147/dmso.s443755] [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: 11/01/2023] [Accepted: 01/24/2024] [Indexed: 02/29/2024] Open
Abstract
Purpose Gestational diabetes mellitus (GDM) is common pregnancy complication (8%), characterized by hyperglycemia resulting from pathological homeostatic mechanisms. There's a concerning trend of increasing GDM prevalence. New markers, particularly epigenetic ones, are sought for early detection and enhanced care. miRNA are small non-coding RNA molecules. The main goal was to investigate the potential role of miRNA (miR-16-5p, miR-222-3p, miR-21-5p) in GDM and their association with clinical features. Patients and Methods The study included 72 pregnant patients, with 42 having GDM and 30 in the control group. miRNA expression was measured using ELISA. Results There were no significant differences in miR-222-3p expression between GDM patients and the control group. The GDM group exhibited a positive correlation between miR-16-5p expression and miR-21-5p expression as well as between miR-16-5p expression and insulin resistance. In the GDM group, a positive correlation was observed between miR-21-5p expression and fasting glucose levels. Conclusion Results do not confirm the role of miR-222-3p in GDM pathogenesis or as a diagnostic marker. Additionally, a role for miR-16-5p in GDM pathogenesis was observed. Furthermore, a potential role for miR-21-5p in monitoring GDM treatment is indicated.
Collapse
Affiliation(s)
- Mateusz Kunysz
- Department of Obstetrics & Gynecology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, Rzeszow, 35-959, Poland
| | - Marek Cieśla
- College of Medical Sciences, University of Rzeszow, Rzeszow, 35-959, Poland
| | - Dorota Darmochwał-Kolarz
- Department of Obstetrics & Gynecology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, Rzeszow, 35-959, Poland
| |
Collapse
|
7
|
Zhao X, Wang Z, Ji X, Bu S, Fang P, Wang Y, Wang M, Yang Y, Zhang W, Leung AY, Shi P. Discrete single-cell microRNA analysis for phenotyping the heterogeneity of acute myeloid leukemia. Biomaterials 2022; 291:121869. [DOI: 10.1016/j.biomaterials.2022.121869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 10/14/2022] [Accepted: 10/19/2022] [Indexed: 11/28/2022]
|
8
|
Wang X, Yang L, Wang Y. Meta-analysis of the diagnostic value of 18F-FDG PET/CT in the recurrence of epithelial ovarian cancer. Front Oncol 2022; 12:1003465. [PMID: 36419900 PMCID: PMC9676502 DOI: 10.3389/fonc.2022.1003465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/30/2022] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Ovarian cancer is the leading cause of cancer-related death among gynecologic malignancies. With much evidence suggesting that 18F-FDG PET/CT may be an excellent imaging test for the diagnosis of epithelial ovarian cancer recurrence, we conducted a systematic review and meta-analysis to summarize relevant studies and evaluate the accuracy and application value of 18F-FDG PET/CT in the diagnosis of recurrence of epithelial ovarian cancer. MATERIALS AND METHODS Clinical trials of 18F-FDG PET/CT for the diagnosis of recurrence of epithelial ovarian cancer were systematically searched in PubMed, Embase, Cochrane Library, Web of Science and OVID database. The relevant literature was searched until May 22, 2022. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of the included original studies, and the meta-analysis was performed using a bivariate mixed-effects model and completed in Stata 15.0. RESULTS A total of 17 studies on 18F-FDG PET/CT for the diagnosis of epithelial ovarian cancer recurrence were included in this systematic review, involving 639 patients with epithelial ovarian cancer. Meta-analysis showed that the sensitivity, specificity and area under the curve of 18F-FDG PET/CT for the diagnosis of epithelial ovarian cancer recurrence were 0.88 (95% CI: 0.79 - 0.93), 0.89 (95% CI: 0.72 - 0.96) and 0.94 (95% CI: 0.91- 0.96), respectively. Subgroup analysis showed higher diagnostic efficacy in prospective studies than in retrospective studies, and no significant publication bias was observed in Deeks' funnel plot, with sensitivity analysis revealing the stability of results. Meta regression shows that the heterogeneity of this study comes from study type. CONCLUSION 18F-FDG PET/CT has good diagnostic value in the recurrence of epithelial ovarian cancer.
Collapse
Affiliation(s)
- Xiaoyan Wang
- School of Nursing, Hexi University, Zhangye, China
| | - Lifeng Yang
- School of Nursing, Hexi University, Zhangye, China
| | - Yan Wang
- Peking University First Hospital Ningxia Women and Children's Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan, China
| |
Collapse
|
9
|
Chang JC, Chang HS, Yeh CY, Chang HJ, Cheng WL, Lin TT, Liu CS, Chen ST. Regulation of mitochondrial fusion and mitophagy by intra-tumoral delivery of membrane-fused mitochondria or Midiv-1 enhances sensitivity to doxorubicin in triple-negative breast cancer. Biomed Pharmacother 2022; 153:113484. [PMID: 36076583 DOI: 10.1016/j.biopha.2022.113484] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/25/2022] [Accepted: 07/27/2022] [Indexed: 11/19/2022] Open
Abstract
Increasing mitochondrial fusion by intra-tumoral grafting of membrane-fused mitochondria created with Pep-1 conjugation (P-Mito) contributes to breast cancer treatment, but it needs to be validated. Using mitochondrial division inhibitor-1 (Mdivi-1, Mdi) to disturb mitochondrial dynamics, we showed that the antitumor action of P-Mito in a mouse model of triple-negative breast cancer depends upon mitochondrial fusion and that Mdi treatment alone is ineffective. P-Mito significantly enhanced Doxorubicin (Dox) sensitivity by inducing mitochondrial fusion and mitophagy, and the same efficiency was also achieved with Mdi by inhibiting mitophagy. Cell death was induced via the p53 pathway and AIF nuclear translocation in the case of P-Mito, versus the caspase-dependent pathway for Mdi. Notably, both mitochondrial treatments reduced oxidative stress and blood vessel density of xenograft tumors, especially P-Mito, which was accompanied by inhibition of nuclear factor kappa-B activation. Furthermore, through enrichment analysis, four microRNAs in serum microvesicles induced by P-Mito caused expression of predicted targets via the PI3K-Akt pathway, and significantly impacted regulation of nuclear processes and myeloid cell differentiation. Clustering of gene-sets implicated a major steroid catabolic network. This study showed diverse roles of mitochondria in breast cancer and revealed effective adjuvant therapy targeting mitochondrial fusion and mitophagy.
Collapse
Affiliation(s)
- Jui-Chih Chang
- Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan.
| | - Huei-Shin Chang
- Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan
| | - Cheng-Yi Yeh
- Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan
| | - Hui-Ju Chang
- Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan
| | - Wen-Ling Cheng
- Department of Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50094, Taiwan
| | - Ta-Tsung Lin
- Department of Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50094, Taiwan
| | - Chin-San Liu
- Department of Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50094, Taiwan; Department of Neurology, Changhua Christian Hospital, Changhua 50094, Taiwan; School of Chinese Medicine, Graduate Institute of Chinese Medicine, Graduate Institute of Integrated Medicine, College of Chinese Medicine, Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 40447, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan
| | - Shou-Tung Chen
- Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 50094, Taiwan; Department of Medical Research, Changhua Christian Hospital, Changhua 50094, Taiwan.
| |
Collapse
|
10
|
Wang J, Wang X, Zhang X, Shao T, Luo Y, Wang W, Han Y. Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges. Front Oncol 2022; 12:884369. [PMID: 35692794 PMCID: PMC9175035 DOI: 10.3389/fonc.2022.884369] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 04/25/2022] [Indexed: 12/05/2022] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. Extracellular vesicles (EVs) contain sufficient bioactive substances and are carriers of intercellular information exchange, as well as delivery vehicles for nucleic acids, proteins and drugs. Although EVs show great potential for the treatment of HCC and their role in HCC progression has been extensively studied, there are still many challenges such as time-consuming extraction, difficult storage, easy contamination, and low drug loading rate. We focus on the biogenesis, morphological characteristics, isolation and extraction of EVs and their significance in the progression of HCC, tumor invasion, immune escape and cancer therapy for a review. EVs may be effective biomarkers for molecular diagnosis of HCC and new targets for tumor-targeted therapy.
Collapse
Affiliation(s)
- Juan Wang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xiaoya Wang
- Clinical Medicine, Southwest Medical University, Luzhou, China
| | - Xintong Zhang
- Clinical Medicine, Southwest Medical University, Luzhou, China
| | - Tingting Shao
- Clinical Medicine, Southwest Medical University, Luzhou, China
| | - Yanmei Luo
- Clinical Medicine, Southwest Medical University, Luzhou, China
| | - Wei Wang
- Clinical Medicine, Southwest Medical University, Luzhou, China
| | - Yunwei Han
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Department of Oncology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Academician (Expert) Workstation of Sichuan Province, Luzhou, China.,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China.,School of Basic Medical Sciences, Shandong University, Jinan, China
| |
Collapse
|
11
|
Teenan O, Sahni V, Henderson RB, Conway BR, Moran CM, Hughes J, Denby L. Sonoporation of Human Renal Proximal Tubular Epithelial Cells In Vitro to Enhance the Liberation of Intracellular miRNA Biomarkers. ULTRASOUND IN MEDICINE & BIOLOGY 2022; 48:1019-1032. [PMID: 35307235 DOI: 10.1016/j.ultrasmedbio.2022.01.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 01/11/2022] [Accepted: 01/29/2022] [Indexed: 06/14/2023]
Abstract
Ultrasound has previously been demonstrated to non-invasively cause tissue disruption. Small animal studies have demonstrated that this effect can be enhanced by contrast microbubbles and has the potential to be clinically beneficial in techniques such as targeted drug delivery or enhancing liquid biopsies when a physical biopsy may be inappropriate. Cavitating microbubbles in close proximity to cells increases membrane permeability, allowing small intracellular molecules to leak into the extracellular space. This study sought to establish whether cavitating microbubbles could liberate cell-specific miRNAs, augmenting biomarker detection for non-invasive liquid biopsies. Insonating human polarized renal proximal tubular epithelial cells (RPTECs), in the presence of SonoVue microbubbles, revealed that cellular health could be maintained while achieving the release of miRNAs, miR-21, miR-30e, miR-192 and miR-194 (respectively, 10.9-fold, 7.17-fold, 5.95-fold and 5.36-fold). To examine the mechanism of release, RPTECs expressing enhanced green fluorescent protein were generated and the protein successfully liberated. Cell polarization, cellular phenotype and cell viability after sonoporation were measured by a number of techniques. Ultrastructural studies using electron microscopy showed gap-junction disruption and pore formation on cellular surfaces. These studies revealed that cell-specific miRNAs can be non-specifically liberated from RPTECs by sonoporation without a significant decrease in cell viability.
Collapse
Affiliation(s)
- Oliver Teenan
- Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK
| | - Vishal Sahni
- GlaxoSmithKline, Medical Research Centre, Stevenage, UK
| | | | - Bryan R Conway
- Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK
| | - Carmel M Moran
- Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK
| | - Jeremy Hughes
- Centre for Inflammation Research, University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK
| | - Laura Denby
- Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
| |
Collapse
|
12
|
Ng SS, Lee HL, Pandian BR, Doong RA. Recent developments on nanomaterial-based optical biosensor as potential Point-of-Care Testing (PoCT) probe in carcinoembryonic antigen detection: A review. Chem Asian J 2022; 17:e202200287. [PMID: 35471591 DOI: 10.1002/asia.202200287] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/25/2022] [Indexed: 11/09/2022]
Abstract
For the past decades, several cancer biomarkers have been exploited for rapid and accurate prognosis or diagnosis purposes. In this review, the optical biosensor is targeted for carcinoembryonic antigen (CEA) detection. The CEA level is a prominent parameter currently used in clinical cases for the prognosis of cancer-related diseases. Many nanomaterial-based biosensors are invented as alternatives for the commonly used enzyme-linked immunosorbent assays (ELISA) immunoassay method in CEA detection as the traditional approach but they possess certain drawbacks such as tedious procedure, high technical demand, and costly. Nevertheless, the effort appears to be wasted as none of them are being actualised. Generally, the sensor function was carried out by converting bio-signals generated upon the interface of the receptor into light signals. These sensors were popular due to specific advantages such as sensitivity, being free from chemical and electromagnetic interferences, wide dynamic range, and being easy to be monitored. The features of PoC diagnostics are discussed and associated with the various applications of colorimetric-based and chemiluminescent-based biosensors. The roles of nanomaterials in each application were also summarised by comparing the modification, incubation period, lowest detection limit (LOD) and linear range of detection amount. The challenges and future perspectives were highlighted at the end of the review.
Collapse
Affiliation(s)
- Siew Suan Ng
- National Tsing Hua University, Department of Analytical and Environmental Science, TAIWAN
| | - Hooi Ling Lee
- Universiti Sains Malaysia, School of Chemical Sciences, School of Chemical Sciences,, Universiti Sains Malaysia,, 11800, USM, MALAYSIA
| | | | - Ruey-An Doong
- National Tsing Hua University, Department of Analytical and Environmental Science, TAIWAN
| |
Collapse
|
13
|
Pozniak T, Shcharbin D, Bryszewska M. Circulating microRNAs in Medicine. Int J Mol Sci 2022; 23:ijms23073996. [PMID: 35409354 PMCID: PMC8999557 DOI: 10.3390/ijms23073996] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 02/04/2023] Open
Abstract
Circulating microRNAs (c-microRNAs, c-miRNAs), which are present in almost all biological fluids, are promising sensitive biomarkers for various diseases (oncological and cardiovascular diseases, neurodegenerative pathologies, etc.), and their signatures accurately reflect the state of the body. Studies of the expression of microRNA markers show that they can enable a wide range of diseases to be diagnosed before clinical symptoms are manifested, and they can help to assess a patient’s response to therapy in order to correct and personalize treatments. This review discusses the latest trends in the uses of miRNAs for diagnosing and treating various diseases, viral and non-viral. It is concluded that exogenous microRNAs can be used as high-precision therapeutic agents for these purposes.
Collapse
Affiliation(s)
- Tetiana Pozniak
- Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus, 220072 Minsk, Belarus
- Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 02000 Kyiv, Ukraine
- Correspondence: (T.P.); (D.S.)
| | - Dzmitry Shcharbin
- Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus, 220072 Minsk, Belarus
- Correspondence: (T.P.); (D.S.)
| | - Maria Bryszewska
- Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland;
| |
Collapse
|
14
|
Circulating miR-146a expression as a non-invasive predictive biomarker for acute lymphoblastic leukemia. Sci Rep 2021; 11:22783. [PMID: 34815474 PMCID: PMC8611079 DOI: 10.1038/s41598-021-02257-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 10/27/2021] [Indexed: 01/10/2023] Open
Abstract
Dysregulation of non-coding microRNAs during the course of tumor development, invasion and/or progression to the distant organs, makes them a promising candidate marker for the diagnosis of cancer and associated malignancies. This exploratory study aims at evaluating the usefulness of plasma concentration of circulating mir-146a as a non-invasive biomarker for acute lymphoblastic leukemia (ALL). Total RNA including miRNA was isolated from 110 plasma samples of patients (n = 66), healthy controls (n = 24) and follow up (n = 20) cases and reverse transcribed. Relative concentrations were assessed using real-time quantitative PCR and fold-change was calculated by 2−ΔΔCt method. Finally, relative concentrations were correlated to clinicopathological factors. Patients (n = 66) were analyzed to determine fold expression of miR-146a in plasma samples of ALL. Before chemotherapy, pediatric (n = 42) and adult (n = 24) showed overexpression of miR-146a compared with healthy controls (P < 0.0001). There was no effect of age and gender on mir-146a expression in plasma. mirR-146a expression was independent of clinical and hematological features. Moreover, miR-146a levels in plasma of paired samples (n = 20) after treatment showed significant decrease in expression (P < 0.001). Expression of plasma miR-146a may be utilized as non-invasive marker to diagnose and predict prognosis in pediatric and adult patients with ALL. Moreover predicted targets may be utilized for ALL therapy in future.
Collapse
|
15
|
Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature. Int J Mol Sci 2021; 22:ijms222212165. [PMID: 34830046 PMCID: PMC8621893 DOI: 10.3390/ijms222212165] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/24/2021] [Accepted: 11/04/2021] [Indexed: 02/07/2023] Open
Abstract
Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to β-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.
Collapse
|
16
|
Molina E, Hong L, Chefetz I. NUAK Kinases: Brain-Ovary Axis. Cells 2021; 10:cells10102760. [PMID: 34685740 PMCID: PMC8535158 DOI: 10.3390/cells10102760] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/07/2021] [Accepted: 10/11/2021] [Indexed: 12/12/2022] Open
Abstract
Liver kinase B (LKB1) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) are two major kinases that regulate cellular metabolism by acting as adenosine triphosphate (ATP) sensors. During starvation conditions, LKB1 and AMPK activate different downstream pathways to increase ATP production, while decreasing ATP consumption, which abrogates cellular proliferation and cell death. Initially, LKB1 was considered to be a tumor suppressor due to its loss of expression in various tumor types. Additional studies revealed amplifications in LKB1 and AMPK kinases in several cancers, suggesting a role in tumor progression. The AMPK-related proteins were described almost 20 years ago as a group of key kinases involved in the regulation of cellular metabolism. As LKB1-downstream targets, AMPK-related proteins were also initially considered to function as tumor suppressors. However, further research demonstrated that AMPK-related kinases play a major role not only in cellular physiology but also in tumor development. Furthermore, aside from their role as regulators of metabolism, additional functions have been described for these proteins, including roles in the cell cycle, cell migration, and cell death. In this review, we aim to highlight the major role of AMPK-related proteins beyond their functions in cellular metabolism, focusing on cancer progression based on their role in cell migration, invasion, and cell survival. Additionally, we describe two main AMPK-related kinases, Novel (nua) kinase family 1 (NUAK1) and 2 (NUAK2), which have been understudied, but play a major role in cellular physiology and tumor development.
Collapse
Affiliation(s)
- Ester Molina
- The Hormel Institute, University of Minnesota, Austin, MN 55912, USA;
| | - Linda Hong
- School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA;
| | - Ilana Chefetz
- The Hormel Institute, University of Minnesota, Austin, MN 55912, USA;
- Masonic Cancer Center, Minneapolis, MN 55455, USA
- Stem Cell Institute, Minneapolis, MN 55455, USA
- Department of Obstetrics, Gynecology and Women’s Health, University of Minnesota, Minneapolis, MN 55455, USA
- Correspondence: ; Tel.: +1-507-437-9624
| |
Collapse
|
17
|
Smit-McBride Z, Morse LS. MicroRNA and diabetic retinopathy-biomarkers and novel therapeutics. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1280. [PMID: 34532417 PMCID: PMC8421969 DOI: 10.21037/atm-20-5189] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 01/14/2021] [Indexed: 01/10/2023]
Abstract
Diabetic retinopathy (DR) accounts for ~80% of legal blindness in persons aged 20-74 years and is associated with enormous social and health burdens. Current therapies are invasive, non-curative, and in-effective in 15-25% of DR patients. This review outlines the potential utility of microRNAs (miRNAs) as biomarkers and potential therapy for diabetic retinopathy. miRNAs are small noncoding forms of RNA that may play a role in the pathogenesis of DR by altering the level of expression of genes via single nucleotide polymorphism and regulatory loops. A majority of miRNAs are intracellular and specific intracellular microRNAs have been associated with cellular changes associated with DR. Some microRNAs are extracellular and called circulatory microRNAs. Circulatory miRNAs have been found to be differentially expressed in serum and bodily fluid in patients with diabetes mellitus (DM) with and without retinopathy. Some miRNAs have been associated with the severity of DR, and future studies may reveal whether circulatory miRNAs could serve as novel reliable biomarkers to detect or predict retinopathy progression. Therapeutic strategies can be developed utilizing the natural miRNA/long noncoding RNA (lncRNA) regulatory loops. miRNAs and lncRNAs are two major families of the non-protein-coding transcripts. They are regulatory molecules for fundamental cellular processes via a variety of mechanisms, and their expression and function are tightly regulated. The recent evidence indicates a cross-talk between miRNAs and lncRNAs. Therefore, dysregulation of miRNAs and lncRNAs is critical to human disease pathogenesis, such as diabetic retinopathy. miRNAs are long-distance communicators and reprogramming agents, and they embody an entirely novel paradigm in cellular and tissue signaling and interaction. By targeting specific miRNAs, whole pathways implicated in the pathogenesis of DR may potentially be altered. Understanding the endogenous roles of miRNAs in the pathogenesis of diabetic retinopathy could lead to novel diagnostic and therapeutic approaches to managing this frequently blinding retinal condition.
Collapse
Affiliation(s)
- Zeljka Smit-McBride
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, USA
| | - Lawrence S Morse
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, USA
| |
Collapse
|
18
|
Margaritis K, Margioula-Siarkou G, Margioula-Siarkou C, Petousis S, Kotanidou EP, Christoforidis A, Pavlou E, Galli-Tsinopoulou A. Circulating serum and plasma levels of micro-RNA in type-1 diabetes in children and adolescents: A systematic review and meta-analysis. Eur J Clin Invest 2021; 51:e13510. [PMID: 33565089 DOI: 10.1111/eci.13510] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/26/2021] [Accepted: 02/05/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) is a complex metabolic disorder characterized by hyperglycaemia, with constantly increasing incidence in paediatric population. The discovery of new molecules, such as microRNAs, and their possible interactions with T1DM create novel aspects in the diagnosis of the disease. METHODS This systematic review and meta-analysis adhered to PRISMA guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and Clinicaltrials.gov. were searched up to 20 April 2020. Inclusion criteria for individual studies were quantification of microRNAs in serum/plasma samples and study groups consisting of children and adolescents with T1DM and healthy controls. Primary outcome of the study was the qualitative expression of microRNAs between the two groups. Statistical analysis was performed with Comprehensive Meta-Analysis Software v3.0. Methodological quality of included studies was assessed using Newcastle-Ottawa scale. RESULTS A total of 484 studies were retrieved from the initial search of the databases. These were subsequently limited to seven included studies. Seven microRNAs demonstrated contrasting expression between the two groups, with two of them showing significant overexpression in T1DM group (miR-181:95% CI: 0.429 to 1.341 P < .001, miR-210:95% CI: 0.381 to 0.852, P < .001) and one micro-RNA being significantly overexpressed in control group (miR-375:95% CI: 0.293 to 1.459, P = .003). CONCLUSION A total of three micro-RNA molecules appeared to have a significantly different expression in T1DM patients, serving as a possible diagnostic panel of biomarkers. These findings may contribute as reference for future research to further support the use of microRNAs as a novel diagnostic tool in T1DM.
Collapse
Affiliation(s)
- Kosmas Margaritis
- 2nd Department of Paediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - Georgia Margioula-Siarkou
- 2nd Department of Obstetrics and Gynecology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Ippokratio General Hospital, Thessaloniki, Greece
| | - Chrysoula Margioula-Siarkou
- 2nd Department of Obstetrics and Gynecology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Ippokratio General Hospital, Thessaloniki, Greece
| | - Stamatios Petousis
- 2nd Department of Obstetrics and Gynecology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Ippokratio General Hospital, Thessaloniki, Greece
| | - Eleni P Kotanidou
- 2nd Department of Paediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - Athanasios Christoforidis
- 1st Department of Paediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Ippokratio General Hospital, Thessaloniki, Greece
| | - Evangelos Pavlou
- 2nd Department of Paediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| | - Assimina Galli-Tsinopoulou
- 2nd Department of Paediatrics, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, Greece
| |
Collapse
|
19
|
Ivanov YD, Romanova TS, Malsagova KA, Pleshakova TO, Archakov AI. Use of Silicon Nanowire Sensors for Early Cancer Diagnosis. Molecules 2021; 26:3734. [PMID: 34207397 PMCID: PMC8234636 DOI: 10.3390/molecules26123734] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 06/10/2021] [Accepted: 06/16/2021] [Indexed: 11/17/2022] Open
Abstract
The review covers some research conducted in the field of medical and biomedical application of devices based on silicon sensor elements (Si-NW-sensors). The use of Si-NW-sensors is one of the key methods used in a whole range of healthcare fields. Their biomedical use is among the most important ones as they offer opportunities for early diagnosis of oncological pathologies, for monitoring the prescribed therapy and for improving the people's quality of life.
Collapse
Affiliation(s)
| | | | - Kristina A. Malsagova
- Institute of Biomedical Chemistry, 119121 Moscow, Russia; (Y.D.I.); (T.S.R.); (T.O.P.); (A.I.A.)
| | | | | |
Collapse
|
20
|
Tran HV, Piro B. Recent trends in application of nanomaterials for the development of electrochemical microRNA biosensors. Mikrochim Acta 2021; 188:128. [PMID: 33740140 DOI: 10.1007/s00604-021-04784-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 03/10/2021] [Indexed: 01/10/2023]
Abstract
The biology of the late twentieth century was marked by the discovery in 1993 of a new class of small non-coding ribonucleic acids (RNAs) which play major roles in regulating the translation and degradation of messenger RNAs. These small RNAs (18-25 nucleotides), called microRNAs (miRNAs), are implied in several biological processes such as differentiation, metabolic homeostasis, or cellular apoptosis and proliferation. The discovery in 2008 that the presence of miRNAs in body fluids could be correlated with cancer (prostate, breast, colon, lung, etc.) or other diseases (diabetes, heart diseases, etc.) has made them new key players as biomarkers. Therefore, miRNA detection is of considerable significance in both disease diagnosis and in the study of miRNA function. Until these days, more than 1200 miRNAs have been identified. However, traditional methods developed for conventional DNA does not apply satisfactorily for miRNA, in particular due to the low expression level of these miRNA in biofluids, and because they are very short strands. Electrochemical biosensors can provide this sensitivity and also offer the advantages of mass fabrication, low-cost, and potential decentralized analysis, which has wide application for microRNAs sensing, with many promising results already reported. The present review summarizes some newly developed electrochemical miRNA detection methods.
Collapse
Affiliation(s)
- Hoang Vinh Tran
- School of Chemical Engineering, Hanoi University of Science and Technology (HUST), 1st Dai Co Viet Road, Hanoi, Vietnam.
| | - Benoit Piro
- ITODYS, CNRS, Université de Paris, F-75006, Paris, France
| |
Collapse
|
21
|
Rishabh K, Khadilkar S, Kumar A, Kalra I, Kumar AP, Kunnumakkara AB. MicroRNAs as Modulators of Oral Tumorigenesis-A Focused Review. Int J Mol Sci 2021; 22:ijms22052561. [PMID: 33806361 PMCID: PMC7961687 DOI: 10.3390/ijms22052561] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 02/24/2021] [Accepted: 02/26/2021] [Indexed: 12/23/2022] Open
Abstract
Oral cancers constitute the majority of head and neck tumors, with a relatively high incidence and poor survival rate in developing countries. While the five-year survival rates of the oral cancer patients have increased to 65%, the overall survival for advanced stages has been at 27% for the past ten years, emphasizing the necessity for further understanding the etiology of the disease, diagnosis, and formulating possible novel treatment regimens. MicroRNAs (miRNAs), a family of small non-coding RNA, have emerged as master modulators of gene expression in various cellular and biological process. Aberrant expression of these dynamic molecules has been associated with many human diseases, including oral cancers. The deregulated miRNAs have been shown to control various oncogenic processes, including sustaining proliferative signaling, evading growth suppressors, resisting cell death activating invasion and metastasis, and inducing angiogenesis. Hence, the aberrant expression of miRNAs associated with oral cancers, makes them potential candidates for the investigation of functional markers, which will aid in the differential diagnosis, prognosis, and development of novel therapeutic regimens. This review presents a holistic insight into our understanding of the role of miRNAs in regulating various hallmarks of oral tumorigenesis.
Collapse
Affiliation(s)
- Kumar Rishabh
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam 781039, India; (K.R.); (S.K.); (A.K.); (I.K.)
| | - Soham Khadilkar
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam 781039, India; (K.R.); (S.K.); (A.K.); (I.K.)
| | - Aviral Kumar
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam 781039, India; (K.R.); (S.K.); (A.K.); (I.K.)
| | - Ishu Kalra
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam 781039, India; (K.R.); (S.K.); (A.K.); (I.K.)
| | - Alan Prem Kumar
- Cancer Science Institute of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore
- National University Cancer Institute, National University Health System, Singapore 119074, Singapore
- Correspondence: authors: (A.P.K.); (A.B.K.)
| | - Ajaikumar B. Kunnumakkara
- Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam 781039, India; (K.R.); (S.K.); (A.K.); (I.K.)
- Correspondence: authors: (A.P.K.); (A.B.K.)
| |
Collapse
|
22
|
Ali A, Hadlich F, Abbas MW, Iqbal MA, Tesfaye D, Bouma GJ, Winger QA, Ponsuksili S. MicroRNA-mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers. Int J Mol Sci 2021; 22:2313. [PMID: 33669156 PMCID: PMC7956714 DOI: 10.3390/ijms22052313] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/22/2021] [Accepted: 02/23/2021] [Indexed: 02/07/2023] Open
Abstract
Pregnancy complications are a major cause of fetal and maternal morbidity and mortality in humans. The majority of pregnancy complications initiate due to abnormal placental development and function. During the last decade, the role of microRNAs (miRNAs) in regulating placental and fetal development has become evident. Dysregulation of miRNAs in the placenta not only affects placental development and function, but these miRNAs can also be exported to both maternal and fetal compartments and affect maternal physiology and fetal growth and development. Due to their differential expression in the placenta and maternal circulation during pregnancy complications, miRNAs can be used as diagnostic biomarkers. However, the differential expression of a miRNA in the placenta may not always be reflected in maternal circulation, which makes it difficult to find a reliable biomarker for placental dysfunction. In this review, we provide an overview of differentially expressed miRNAs in the placenta and/or maternal circulation during preeclampsia (PE) and intrauterine growth restriction (IUGR), which can potentially serve as biomarkers for prediction or diagnosis of pregnancy complications. Using different bioinformatics tools, we also identified potential target genes of miRNAs associated with PE and IUGR, and the role of miRNA-mRNA networks in the regulation of important signaling pathways and biological processes.
Collapse
Affiliation(s)
- Asghar Ali
- Leibniz Institute for Farm Animal Biology, Institute of Genome Biology, 18196 Dummerstorf, Germany
- Animal Reproduction and Biomedical Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Frieder Hadlich
- Leibniz Institute for Farm Animal Biology, Institute of Genome Biology, 18196 Dummerstorf, Germany
| | - Muhammad W Abbas
- Department of Bioinformatics and Biotechnology, Government College University, Faisalabad 38000, Pakistan
| | - Muhammad A Iqbal
- Leibniz Institute for Farm Animal Biology, Institute of Genome Biology, 18196 Dummerstorf, Germany
| | - Dawit Tesfaye
- Animal Reproduction and Biomedical Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Gerrit J Bouma
- Animal Reproduction and Biomedical Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Quinton A Winger
- Animal Reproduction and Biomedical Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
| | - Siriluck Ponsuksili
- Leibniz Institute for Farm Animal Biology, Institute of Genome Biology, 18196 Dummerstorf, Germany
| |
Collapse
|
23
|
Malsagova KA, Popov VP, Kupriyanov IN, Pleshakova TO, Galiullin RA, Kozlov AF, Shumov ID, Larionov DI, Tikhonenko FV, Kapustina SI, Ziborov VS, Petrov OF, Gadzhieva OA, Bashiryan BA, Shimansky VN, Archakov AI, Ivanov YD. Raman Spectroscopy-Based Quality Control of "Silicon-On-Insulator" Nanowire Chips for the Detection of Brain Cancer-Associated MicroRNA in Plasma. SENSORS (BASEL, SWITZERLAND) 2021; 21:1333. [PMID: 33668578 PMCID: PMC7918486 DOI: 10.3390/s21041333] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/09/2021] [Accepted: 02/11/2021] [Indexed: 12/21/2022]
Abstract
Application of micro-Raman spectroscopy for the monitoring of quality of nanowire sensor chips fabrication has been demonstrated. Nanowire chips have been fabricated on the basis of «silicon-on-insulator» (SOI) structures (SOI-NW chips). The fabrication of SOI-NW chips was performed by optical litography with gas-phase etching. The so-fabricated SOI-NW chips are intended for highly sensitive detection of brain cancer biomarkers in humans. In our present study, two series of experiments have been conducted. In the first experimental series, detection of a synthetic DNA oligonucleotide (oDNA) analogue of brain cancer-associated microRNA miRNA-363 in purified buffer solution has been performed in order to demonstrate the high detection sensitivity. The second experimental series has been performed in order to reveal miRNA-363 itself in real human plasma samples. To provide detection biospecificity, the SOI-NW chip surface was modified by covalent immobilization of probe oligonucleotides (oDNA probes) complementary to the target biomolecules. Using the SOI-NW sensor chips proposed herein, the concentration detection limit of the target biomolecules at the level of 3.3 × 10-17 M has been demonstrated. Thus, the approach employing the SOI-NW chips proposed herein represents an attractive tool in biomedical practice, aimed at the early revelation of oncological diseases in humans.
Collapse
Affiliation(s)
- Kristina A. Malsagova
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Vladimir P. Popov
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia; (V.P.P.); (F.V.T.)
| | - Igor N. Kupriyanov
- Sobolev Institute of Geology and Mineralogy, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia;
| | - Tatyana O. Pleshakova
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Rafael A. Galiullin
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Andrey F. Kozlov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Ivan D. Shumov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Dmitry I. Larionov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Fedor V. Tikhonenko
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia; (V.P.P.); (F.V.T.)
| | - Svetlana I. Kapustina
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Vadim S. Ziborov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
- Joint Institute for High Temperatures of Russian Academy of Sciences, 125412 Moscow, Russia;
| | - Oleg F. Petrov
- Joint Institute for High Temperatures of Russian Academy of Sciences, 125412 Moscow, Russia;
| | - Olga A. Gadzhieva
- Federal State Autonomous Institution “N. N. Burdenko National Medical Research Center of Neurosurgery” of the Ministry of Health of the Russian Federation, 125047 Moscow, Russia; (O.A.G.); (B.A.B.); (V.N.S.)
| | - Boris A. Bashiryan
- Federal State Autonomous Institution “N. N. Burdenko National Medical Research Center of Neurosurgery” of the Ministry of Health of the Russian Federation, 125047 Moscow, Russia; (O.A.G.); (B.A.B.); (V.N.S.)
| | - Vadim N. Shimansky
- Federal State Autonomous Institution “N. N. Burdenko National Medical Research Center of Neurosurgery” of the Ministry of Health of the Russian Federation, 125047 Moscow, Russia; (O.A.G.); (B.A.B.); (V.N.S.)
| | - Alexander I. Archakov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| | - Yuri D. Ivanov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (D.I.L.); (S.I.K.); (V.S.Z.); (A.I.A.); (Y.D.I.)
| |
Collapse
|
24
|
Extracellular vesicles (EVs): What we know of the mesmerizing roles of these tiny vesicles in hematological malignancies? Life Sci 2021; 271:119177. [PMID: 33577843 DOI: 10.1016/j.lfs.2021.119177] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 01/29/2021] [Accepted: 01/29/2021] [Indexed: 02/07/2023]
Abstract
Cancer is a complex disease in which a bidirectional collaboration between malignant cells and surrounding microenvironment creates an appropriate platform which ultimately facilitates the progression of the disease. The discovery of extracellular vesicles (EVs) was a turning point in the modern era of cancer biology, as their importance in human malignancies has set the stage to widen research interest in the field of cell-to-cell communication. The implication in short- and long-distance interaction via horizontally transfer of cellular components, ranging from non-coding RNAs to functional proteins, as well as stimulating target cells receptors by the means of ligands anchored on their membrane endows these "tiny vesicles with giant impacts" with incredible potential to re-educate normal tissues, and thus, to re-shape the surrounding niche. In this review, we highlight the pathogenic roles of EVs in human cancers, with an extensive focus on the recent advances in hematological malignancies.
Collapse
|
25
|
Malsagova KA, Pleshakova TO, Popov VP, Kupriyanov IN, Galiullin RA, Kozlov AF, Shumov ID, Kaysheva AL, Tikhonenko FV, Archakov AI, Ivanov YD. Optical Monitoring of the Production Quality of Si-Nanoribbon Chips Intended for the Detection of ASD-Associated Oligonucleotides. MICROMACHINES 2021; 12:mi12020147. [PMID: 33546438 PMCID: PMC7913754 DOI: 10.3390/mi12020147] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 01/25/2021] [Accepted: 01/29/2021] [Indexed: 02/07/2023]
Abstract
Gas-phase etching and optical lithography were employed for the fabrication of a silicon nanoribbon chip (Si-NR chip). The quality of the so-fabricated silicon nanoribbons (Si-NRs) was monitored by optical Raman scattering spectroscopy. It was demonstrated that the structures of the Si-NRs were virtually defect-free, meaning they could be used for highly sensitive detection of biological macromolecules. The Si-NR chips were then used for the highly sensitive nanoelectronics detection of DNA oligonucleotides (oDNAs), which represent synthetic analogs of 106a-5p microRNA (miR-106a-5p), associated with the development of autism spectrum disorders in children. The specificity of the analysis was attained by the sensitization of the Si-NR chip sur-face by covalent immobilization of oDNA probes, whose nucleotide sequence was complementary to the known sequence of miR-106a-5p. The use of the Si-NR chip was demonstrated to al-low for the rapid label-free real-time detection of oDNA at ultra-low (~10−17 M) concentrations.
Collapse
Affiliation(s)
- Kristina A. Malsagova
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
- Correspondence: ; Tel.: +7-499-246-3761
| | - Tatyana O. Pleshakova
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
| | - Vladimir P. Popov
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of Russian Academy of Sciences, Laboratory of Silicon Material Science, 630090 Novosibirsk, Russia; (V.P.P.); (F.V.T.)
| | - Igor N. Kupriyanov
- Sobolev Institute of Geology and Mineralogy, Siberian Branch of Russian Academy of Sciences, Laboratory of Experimental Mineralogy and Crystallogenesis, 630090 Novosibirsk, Russia;
| | - Rafael A. Galiullin
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
| | - Andrey F. Kozlov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
| | - Ivan D. Shumov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
| | - Anna L. Kaysheva
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
| | - Fedor V. Tikhonenko
- Rzhanov Institute of Semiconductor Physics, Siberian Branch of Russian Academy of Sciences, Laboratory of Silicon Material Science, 630090 Novosibirsk, Russia; (V.P.P.); (F.V.T.)
| | - Alexander I. Archakov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
| | - Yuri D. Ivanov
- Laboratory of Nanobiotechnology, Institute of Biomedical Chemistry, 119121 Moscow, Russia; (T.O.P.); (R.A.G.); (A.F.K.); (I.D.S.); (A.L.K.); (A.I.A.); (Y.D.I.)
| |
Collapse
|
26
|
Zhao X, Xiao Z, Li B, Li H, Yang B, Li T, Mei Z. miRNA-21 may serve as a promising noninvasive marker of glioma with a high diagnostic performance: a pooled analysis of 997 patients. Ther Adv Med Oncol 2021; 13:1758835920987650. [PMID: 33613699 PMCID: PMC7871292 DOI: 10.1177/1758835920987650] [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: 07/18/2020] [Accepted: 12/17/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Although various serum and tissue biomarkers have been investigated for
glioma diagnosis, no gold standard has been identified. miRNA-21 was
demonstrated to be a promising biomarker for the diagnosis of various brain
tumors, whereas there remains uncertainty concerning whether miRNA-21 could
be used as a good clinical diagnostic biomarker for glioma. The current
meta-analysis aimed to evaluate the diagnostic accuracy of miRNA-21 as a
potent biomarker in adults with suspected glioma. Methods: The Pubmed and Embase databases were searched systematically from inception
to January 2020 to identify relevant research reports. Pooled sensitivity,
specificity, positive likelihood ratio (PLR), negative likelihood ratio
(NLR), and diagnostic odds ratio (DOR) were calculated. Summary receiver
operating characteristic (SROC) curves were used to evaluate the overall
diagnostic performance. Meta-regression and subgroup analyses were conducted
to determine the source of heterogeneity and test the robustness of the
results. Results: From 5394 citations with 997 subjects that met the inclusion criteria, 11
studies were selected. Summary estimates of the diagnostic performance of
miRNA-21 were as follows: sensitivity, 0.83 [95% confidence interval (CI):
0.73–0.89]; specificity, 0.92 (95% CI: 0.85–0.96); PLR, 10.20 (95% CI:
5.10–20.30); NLR, 0.19 (95% CI: 0.12–0.31); and DOR, 54 (95% CI: 19–155).
The area under the SROC curve was 0.94 (95% CI: 0.92–0.96). Deeks’s funnel
plot revealed no evidence of publication bias (p = 0.59).
Meta-regression analysis suggested that study publication year could
attribute to the heterogeneity. Subgroup analysis found miRNA-21 had a
constant high diagnostic accuracy across different ethnicity, glioma grade,
sample source, and study region. Conclusion: This meta-analysis demonstrated that miRNA-21 has high diagnostic performance
and could serve as a promising noninvasive diagnostic marker for glioma.
Further large prospective studies are needed to validate its diagnostic
value and its prognostic significance and therapeutic effects.
Collapse
Affiliation(s)
- Xinli Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Zhihong Xiao
- Department of Spine Surgery, The Second Affiliated Hospital, University of South China, Hengyang, Hunan, China
| | - Bin Li
- Department of Neurosurgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Hongwei Li
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Bo Yang
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan Province, 450052, China
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, No. 169 Changle West Road, Xi'an 710032, China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Anorectal Disease Institute of Shuguang Hospital, 528 Zhangheng Road, Shanghai 201203, China
| |
Collapse
|
27
|
Zhang X, Dang Y, Liu R, Zhao S, Ma J, Qin Y. MicroRNA-127-5p impairs function of granulosa cells via HMGB2 gene in premature ovarian insufficiency. J Cell Physiol 2020; 235:8826-8838. [PMID: 32391592 DOI: 10.1002/jcp.29725] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 04/10/2020] [Indexed: 12/30/2022]
Abstract
Distinct microRNA (miRNA) profiles have been reported in premature ovarian insufficiency (POI), but their functional relevance in POI is not yet clearly stated. In this study, aberrant expressions of miR-127-5p and high mobility group box 2 (HMGB2) were observed by microarrays in granulosa cells (GCs) from biochemical POI (bPOI) women and further confirmed by a quantitative reverse-transcription polymerase chain reaction. Immortalized human granulosa cell line and mouse primary ovarian GCs were used for functional validation. Orthotopic mouse model was established to examine the role of miR-127-5p in vivo. Finally, the expression of miR-127-5p was measured in the plasma of bPOI women. The receiver operating characteristic curve analysis was performed to determine the indicative role of miR-127-5p for ovarian reserve. Results showed the upregulation of miR-127-5p was identified in GCs from bPOI patients. It inhibited GCs proliferation and impaired DNA damage repair capacity through targeting HMGB2, which was significantly downregulated in GCs from the same cohort of cases. miR-127-5p was confirmed to attenuate DNA repair capability via HMGB2 in mouse ovary in vivo. Intriguingly, the upexpression of miR-127-5p was also detected in plasma of bPOI individuals, suggesting that miR-127-5p could be a promising indicator for bPOI. Taken together, our results discovered the deleterious effects of miR-127-5p on GCs function and its predictive value in POI process. The target gene HMGB2 could be considered as a new candidate for POI. This study highlights the importance of DNA repair capacity for ovarian function and sheds light on the epigenetic mechanism in the pathogenicity of POI.
Collapse
Affiliation(s)
- Xinyue Zhang
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China
- Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, Shandong, China
| | - Yujie Dang
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China
- Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, Shandong, China
| | - Ran Liu
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China
- Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, Shandong, China
| | - Shidou Zhao
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China
- Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, Shandong, China
| | - Jinlong Ma
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China
- Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, Shandong, China
| | - Yingying Qin
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China
- Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, Shandong, China
| |
Collapse
|
28
|
Astamal RV, Maghoul A, Taefehshokr S, Bagheri T, Mikaeili E, Derakhshani A, Delashoub M, Taefehshokr N, Isazadeh A, Hajazimian S, Tran A, Baradaran B. Regulatory role of microRNAs in cancer through Hippo signaling pathway. Pathol Res Pract 2020; 216:153241. [PMID: 33065484 DOI: 10.1016/j.prp.2020.153241] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/29/2020] [Accepted: 10/04/2020] [Indexed: 12/18/2022]
Abstract
Cancer is the major cause of death worldwide in countries of all income levels. The Hippo signaling pathway is a Drosophila kinase gene that was identified to regulate organ size, cell regeneration, and contribute to tumorigenesis. A huge variety of extrinsic and intrinsic signals regulate the Hippo signaling pathway. The Hippo signaling pathway consists of a wide array of components that merge numerous signals such as mechanical signals to address apoptosis resistance, cell proliferation, cellular outputs of growth, cell death and survival at cellular and tissue level. Recent studies have shed new light on the regulatory role of microRNAs in Hippo signaling and how they contribute to cancer progression. MicroRNAs influence various cancer-related processes such as, apoptosis, proliferation, migration, cell cycle and metabolism. Inhibition and overexpression of miRNAs via miRNA mimics and miRNA inhibitors, respectively, can uncover a hopeful and reliable insight for treatment and early diagnosis of cancer patients. In this review we will discuss our current understanding of regulatory role of miRNAs in Hippo signaling pathway.
Collapse
Affiliation(s)
- Reza Vaezi Astamal
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Asma Maghoul
- Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran; Department of Basic Sciences, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Sina Taefehshokr
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taha Bagheri
- Department of Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Ehsan Mikaeili
- Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Afshin Derakhshani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Delashoub
- Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran; Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
| | - Nima Taefehshokr
- Department of Microbiology and Immunology, Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
| | - Alireza Isazadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saba Hajazimian
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Antalique Tran
- Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT, 06536, USA
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
29
|
Shuai Y, Liao L, Su X, Sha N, Li X, Wu Y, Jing H, Kuang H, Deng Z, Li Y, Jin Y. Circulating microRNAs in serum as novel biomarkers for osteoporosis: a case-control study. Ther Adv Musculoskelet Dis 2020; 12:1759720X20953331. [PMID: 33029202 PMCID: PMC7522822 DOI: 10.1177/1759720x20953331] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 08/05/2020] [Indexed: 02/05/2023] Open
Abstract
AIMS Osteoporosis is underdiagnosed because of the lack of a convenient diagnostic method. Circulating microRNAs (miRNAs) emerge as novel biomarkers for disease diagnosis. Here, we conducted a case-control study that included a total of 448 serum samples collected from 182 healthy participants, 132 osteopenia participants, and 134 osteoporosis patients. METHODS Circulating miRNAs dysregulated during osteoporosis were screened and analyzed in three randomly determined sub-cohorts: the discovery cohort identified 22 candidate miRNAs; the training cohort tested the candidate miRNAs and constructed Index 1, comprising five miRNAs by logistic regression, and Index 2, comprising four miRNAs, was developed by linear combination. RESULTS Both indices were tested in the validation cohort and showed statistically significant results in distinguishing osteoporosis patients from healthy and osteopenic patients. Moreover, Index 1 also showed improved performance over traditional bone turnover biomarkers type I pro-collagen (tPINP) and type I collagen (β-CTx). CONCLUSION In conclusion, circulating miRNAs are potential biomarkers for osteoporosis. The diagnostic panel of circulating miRNAs could be a complementary method for dual-energy X-ray absorptiometry (DXA) in mass screening and routine examination to enhance the osteoporosis detection rate.
Collapse
Affiliation(s)
- Yi Shuai
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Li Liao
- State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoxia Su
- State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Nanxi Sha
- Department of Health Medical Center, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Xiaobo Li
- Department of Health Medical Center, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Yutao Wu
- State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Huan Jing
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Huijuan Kuang
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Zhihong Deng
- Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China
| | - Yongqi Li
- Department of Pediatric, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yan Jin
- State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, 145# West Changle Road, Xi'an, Shaanxi 710032, China
| |
Collapse
|
30
|
Smit-McBride Z, Nguyen AT, Yu AK, Modjtahedi SP, Hunter AA, Rashid S, Moisseiev E, Morse LS. Unique molecular signatures of microRNAs in ocular fluids and plasma in diabetic retinopathy. PLoS One 2020; 15:e0235541. [PMID: 32692745 PMCID: PMC7373301 DOI: 10.1371/journal.pone.0235541] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 06/18/2020] [Indexed: 12/13/2022] Open
Abstract
The main objective of this pilot study was to identify circulatory microRNAs in aqueous or plasma that were reflecting changes in vitreous of diabetic retinopathy patients. Aqueous, vitreous and plasma samples were collected from a total of 27 patients undergoing vitreoretinal surgery: 11 controls (macular pucker or macular hole patients) and 16 with diabetes mellitus(DM): DM-Type I with proliferative diabetic retinopathy(PDR) (DMI-PDR), DM Type II with PDR(DMII-PDR) and DM Type II with nonproliferative DR(DMII-NPDR). MicroRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data were analyzed using Expression Console, Transcriptome Analysis Console, and Ingenuity Pathway Analysis. The comparison analysis of circulatory microRNAs showed that out of a total of 847 human microRNA probes on the microarrays, common microRNAs present both in aqueous and vitreous were identified, and a large number of unique microRNA, dependent on the DM type and severity of retinopathy. Most of the dysregulated microRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, they were downregulated. Dysregulation of miRNAs in aqueous did not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although a few potential candidates for common biomarkers stood out: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed miRNAs that were uniquely dysregulated in each fluid (i.e. aqueous: for DMII-NPDR was miR-455-3p; for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202). Pathway analysis identified TGF-beta and VEGF pathways affected. The comparative profiling of circulatory miRNAs showed that a small number of them displayed differential presence in diabetic retinopathy vs. controls. A pattern is emerging of unique molecular microRNA signatures in bodily fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for diagnostic and therapeutic purposes.
Collapse
Affiliation(s)
- Zeljka Smit-McBride
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Anthony T. Nguyen
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Alfred K. Yu
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Sara P. Modjtahedi
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Allan A. Hunter
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Saadia Rashid
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Elad Moisseiev
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Lawrence S. Morse
- Department of Ophthalmology & Vision Science, Vitreoretinal Research Laboratory, School of Medicine, University of California Davis, Davis, California, United States of America
| |
Collapse
|
31
|
Bai SY, Ji R, Wei H, Guo QH, Yuan H, Chen ZF, Wang YP, Liu Z, Yang XY, Zhou YN. Serum miR-551b-3p is a potential diagnostic biomarker for gastric cancer. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:415-419. [PMID: 31060996 DOI: 10.5152/tjg.2019.17875] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Many studies have demonstrated that serum microRNAs have potential applications as non-invasive biomarkers for cancer diagnosis. The aim of the present study was to investigate the expression of serum miR-551b-3p in patients with GC and to explore its potential as a diagnostic biomarker in GC. MATERIALS AND METHODS The expression of miR-551b-3p was detected using quantitative reverse transcription polymerase chain reaction in preoperative serum samples of 50 patients with GC and 53 healthy individuals. An analysis was performed to determine the correlation between serum miR-551b-3p levels and clinicopathological characteristics of patients with GC. The receiver operating characteristic curve was generated, and the cut-off point of serum miR-551b-3p for the diagnosis of GC was selected. The clinical value of serum miR-551b-3p for GC was analyzed by a consistency test. RESULTS The expression of serum miR-551b-3p was significantly lower in patients with GC than in healthy individuals (p=0.000). Low level was positively associated with tumor size (p=0.014), depth of invasion (p=0.001), and Tumor-Node-Metastasis stage (p=0.022). The area under the curve for serum miR-551b-3p distinguishing patients with GC from healthy individuals was 0.860 (95% CI: 0.787-0.933, p=0.000), with a specificity of 96.2% and a sensitivity of 70%. The kappa consistency test had a kappa value of 0.667 (p=0.000) in GC. CONCLUSION Serum miR-551b-3p may potentially serve as a diagnostic biomarker for GC.
Collapse
Affiliation(s)
- Su-Yang Bai
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| | - Rui Ji
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| | - Hui Wei
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| | - Qing-Hong Guo
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| | - Hao Yuan
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| | - Zhao-Feng Chen
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| | - Yu-Ping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| | - Zheng Liu
- The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu, China
| | - Xiao-Yan Yang
- The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu, China
| | - Yong-Ning Zhou
- Department of Gastroenterology, The First Hospital of Lanzhou University; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou, Gansu, China
| |
Collapse
|
32
|
Yi W, Tu MJ, Liu Z, Zhang C, Batra N, Yu AX, Yu AM. Bioengineered miR-328-3p modulates GLUT1-mediated glucose uptake and metabolism to exert synergistic antiproliferative effects with chemotherapeutics. Acta Pharm Sin B 2020; 10:159-170. [PMID: 31993313 PMCID: PMC6976971 DOI: 10.1016/j.apsb.2019.11.001] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 08/16/2019] [Accepted: 10/31/2019] [Indexed: 12/15/2022] Open
Abstract
MicroRNAs (miRNAs or miRs) are small noncoding RNAs derived from genome to control target gene expression. Recently we have developed a novel platform permitting high-yield production of bioengineered miRNA agents (BERA). This study is to produce and utilize novel fully-humanized BERA/miR-328-3p molecule (hBERA/miR-328) to delineate the role of miR-328-3p in controlling nutrient uptake essential for cell metabolism. We first demonstrated successful high-level expression of hBERA/miR-328 in bacteria and purification to high degree of homogeneity (>98%). Biologic miR-328-3p prodrug was selectively processed to miR-328-3p to suppress the growth of highly-proliferative human osteosarcoma (OS) cells. Besides glucose transporter protein type 1, gene symbol solute carrier family 2 member 1 (GLUT1/SLC2A1), we identified and verified large neutral amino acid transporter 1, gene symbol solute carrier family 7 member 5 (LAT1/SLC7A5) as a direct target for miR-328-3p. While reduction of LAT1 protein levels by miR-328-3p did not alter homeostasis of amino acids within OS cells, suppression of GLUT1 led to a significantly lower glucose uptake and decline in intracellular levels of glucose and glycolytic metabolite lactate. Moreover, combination treatment with hBERA/miR-328 and cisplatin or doxorubicin exerted a strong synergism in the inhibition of OS cell proliferation. These findings support the utility of novel bioengineered RNA molecules and establish an important role of miR-328-3p in the control of nutrient transport and homeostasis behind cancer metabolism.
Collapse
Key Words
- 2-NBDG, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose
- ABCG2, ATP-binding cassette subfamily G member 2
- ACN, acetonitrile
- Au/Uv, absorbance unit of ultraviolet-visible spectroscopy
- BCRP, breast cancer resistant protein
- BERA, bioengineered miRNA agent
- Bioengineered RNA
- CI, combination index
- CPT, cisplatin
- Cancer
- Chemosensitivity
- DOX, doxorubicin
- E. coli, Escherichia coli
- ESI, electrospray ionization
- FPLC, fast protein liquid chromatography
- Fa, fraction affected
- GLUT1
- GLUT1, glucose transporter protein type 1
- HCC, hepatocellular carcinoma
- HPLC, high-performance liquid chromatography
- IS, internal standard
- KRB, Krebs–Ringer bicarbonate
- LAT1
- LAT1, large neutral amino acid transporter 1
- LC–MS/MS, liquid chromatography–tandem mass spectroscopy
- MCT4, monocarboxylate transporter 4
- MRE, miRNA response elements
- MRM, multiple reaction monitoring
- MiR-328
- OS, osteosarcoma
- PAGE, polyacrylamide gel electrophoresis
- PTEN, phosphatase and tensin homolog
- PVDF, Polyvinylidene fluoride
- RAGE, receptor for advanced glycosylation end products
- RT-qPCR, reverse transcription quantitative real-time polymerase chain reaction
- SLC2A1, 7A5, 16A3, solute carrier family 2 member 1, family 7 member 5, family 16 member 3
- WT, wild type
- hBERA, humanized bioengineered miRNA agent
- hsa, Homo sapiens
- htRNASer, human seryl-tRNA
- mTOR, mammalian target of rapamycin
- miR or miRNA, microRNA
- ncRNA, noncoding RNAs
- nt, nucleotide
Collapse
Affiliation(s)
- Wanrong Yi
- Department of Orthopaedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
- Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento 95817, CA, USA
| | - Mei-Juan Tu
- Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento 95817, CA, USA
| | - Zhenzhen Liu
- Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento 95817, CA, USA
| | - Chao Zhang
- Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento 95817, CA, USA
| | - Neelu Batra
- Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento 95817, CA, USA
| | - Ai-Xi Yu
- Department of Orthopaedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Ai-Ming Yu
- Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento 95817, CA, USA
| |
Collapse
|
33
|
Elfar M, Amleh A. miR-590-3p and Its Downstream Target Genes in HCC Cell Lines. Anal Cell Pathol (Amst) 2019; 2019:3234812. [PMID: 31781476 PMCID: PMC6875279 DOI: 10.1155/2019/3234812] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 09/17/2019] [Indexed: 12/24/2022] Open
Abstract
miRNAs are small non-coding RNA sequences of 18-25 nucleotides. They can regulate different cellular pathways by acting on tumor suppressors, oncogenes, or both. miRNAs are mostly tissue-specific, and their expression varies depending on the cancer or the tissue in which they are found. hsa-miR-590-3p was found to be involved in several types of cancers. In this study, we identified potential downstream target genes of hsa-miR-590-3p computationally. Several bioinformatics tools and more than one approach were used to identify potential downstream target genes of hsa-miR-590-3p. CX3CL1, SOX2, N-cadherin, E-cadherin, and FOXA2 were utilized as potential downstream target genes of hsa-miR-590-3p. SNU449 and HepG2, hepatocellular carcinoma cell lines, were used to carry out various molecular techniques to further validate our in silico results. mRNA and protein expression levels of these genes were detected using RT-PCR and western blotting, respectively. Co-localization of hsa-miR-590-3p and its candidate downstream target gene, SOX2, was carried out using a miRNA in situ hybridization combined with immunohistochemistry staining through anti-SOX2. The results show that there is an inverse correlation between hsa-miR-590-3p expression and SOX2 protein expression in SNU449. Subsequently, we suggest that SOX2 can be a direct downstream target of has-miR-590-3p indicating that it may have a role in the self-renewal and self-maintenance of cancer cells. We also suggest that CX3CL1, E-cadherin, N-cadherin, and FOXA2 show a lot of potential as downstream target genes of hsa-miR-590-3p signifying its role in epithelial-mesenchymal transition. Studying the expression of hsa-miR-590-3p downstream targets can enrich our understanding of the cancer pathogenesis and how it can be used as a therapeutic tool.
Collapse
Affiliation(s)
- Mennatallah Elfar
- Biotechnology Program, The American University in Cairo, Cairo, Egypt
| | - Asma Amleh
- Biotechnology Program, The American University in Cairo, Cairo, Egypt
- Biology Department, The American University in Cairo, Cairo, Egypt
| |
Collapse
|
34
|
Jain G, Stuendl A, Rao P, Berulava T, Pena Centeno T, Kaurani L, Burkhardt S, Delalle I, Kornhuber J, Hüll M, Maier W, Peters O, Esselmann H, Schulte C, Deuschle C, Synofzik M, Wiltfang J, Mollenhauer B, Maetzler W, Schneider A, Fischer A. A combined miRNA-piRNA signature to detect Alzheimer's disease. Transl Psychiatry 2019; 9:250. [PMID: 31591382 PMCID: PMC6779890 DOI: 10.1038/s41398-019-0579-2] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 06/05/2019] [Accepted: 08/18/2019] [Indexed: 01/03/2023] Open
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild-cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.
Collapse
Affiliation(s)
- Gaurav Jain
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Göttingen, Germany
| | - Anne Stuendl
- 0000 0004 0438 0426grid.424247.3Translational Dementia Research, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
| | - Pooja Rao
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Göttingen, Germany
| | - Tea Berulava
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Göttingen, Germany
| | - Tonatiuh Pena Centeno
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Göttingen, Germany ,Bioinformatics Unit, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Goettingen, Germany
| | - Lalit Kaurani
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Göttingen, Germany
| | - Susanne Burkhardt
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Göttingen, Germany
| | - Ivana Delalle
- 0000 0004 0367 5222grid.475010.7Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Johannes Kornhuber
- 0000 0001 2107 3311grid.5330.5Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Michael Hüll
- 0000 0000 9428 7911grid.7708.8Center for Geriatric Medicine and Gerontology, University Medical Center Freiburg, 79106 Freiburg, Germany ,0000 0000 9428 7911grid.7708.8Department of Psychiatry and Psychotherapy, University Medical Centre Freiburg, 79106 Freiburg, Germany
| | - Wolfgang Maier
- 0000 0001 2240 3300grid.10388.32Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127 Bonn, Germany
| | - Oliver Peters
- 0000 0001 2248 7639grid.7468.dDepartment of Psychiatry, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12200 Berlin, Germany ,0000 0004 0438 0426grid.424247.3German Center for Neurodegenerative Diseases (DZNE), 12203 Berlin, Germany ,0000 0001 1014 0849grid.419491.0Memory Clinic and Dementia Prevention Center, Experimental and Clinical Research Center (ECRC), 13125 Berlin, Germany
| | - Hermann Esselmann
- 0000 0001 0482 5331grid.411984.1Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), 37075 Göttingen, Germany
| | - Claudia Schulte
- 0000 0001 2190 1447grid.10392.39Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, Germany ,0000 0004 0438 0426grid.424247.3German Center for Neurodegenerative Diseases (DZNE), 72076 Tuebingen, Germany
| | - Christian Deuschle
- 0000 0001 2190 1447grid.10392.39Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, Germany ,0000 0004 0438 0426grid.424247.3German Center for Neurodegenerative Diseases (DZNE), 72076 Tuebingen, Germany
| | - Mathis Synofzik
- 0000 0001 2190 1447grid.10392.39Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, Germany ,0000 0004 0438 0426grid.424247.3German Center for Neurodegenerative Diseases (DZNE), 72076 Tuebingen, Germany
| | - Jens Wiltfang
- 0000 0001 0482 5331grid.411984.1Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), 37075 Göttingen, Germany ,0000000123236065grid.7311.4iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal ,German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075 Göttingen, Germany
| | - Brit Mollenhauer
- 0000 0001 0482 5331grid.411984.1Department of Neurology, University Medical Center Göttingen (UMG), 37075 Göttingen, Germany ,grid.440220.0Paracelsus-Elena-Klinik, 34128 Kassel, Germany
| | - Walter Maetzler
- 0000 0001 2190 1447grid.10392.39Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, Germany ,0000 0004 0438 0426grid.424247.3German Center for Neurodegenerative Diseases (DZNE), 72076 Tuebingen, Germany ,0000 0004 0646 2097grid.412468.dDepartment of Neurology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
| | - Anja Schneider
- Translational Dementia Research, German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany. .,Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany.
| | - Andre Fischer
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Goettingen, 37075, Göttingen, Germany. .,Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), 37075, Göttingen, Germany.
| |
Collapse
|
35
|
Wang WT, Guo CQ, Cui GH, Zhao S. Correlation of plasma miR-21 and miR-93 with radiotherapy and chemotherapy efficacy and prognosis in patients with esophageal squamous cell carcinoma. World J Gastroenterol 2019; 25:5604-5618. [PMID: 31602161 PMCID: PMC6785517 DOI: 10.3748/wjg.v25.i37.5604] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/08/2019] [Accepted: 09/10/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the main causes of human death. It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage. Therefore, patients have already lost the best surgical timing when diagnosed. Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically, but the efficacy and prognosis of patients from them are still unsatisfactory. Therefore, it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients.
AIM To explore the clinical value of plasma miR-21 and miR-93 in ESCC.
METHODS A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy, and other 45 healthy people during the same period were enrolled as a control group. The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction, and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed. The receiver operating characteristic (ROC) curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients, the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients, and the Cox regression analysis to identify the prognostic factors for ESCC patients.
RESULTS The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group (P < 0.01). The area under the ROC curve (AUC) of plasma miR-21 for diagnosing T stage, N stage, M stage, and pathological differentiation of ESCC was 0.819, 0.758, 0.824, and 0.725, respectively, and that of plasma miR-93 for diagnosing T stage, N stage, and M stage of ESCC was 0.827, 0.815, and 0.814, respectively. The AUC of combined plasma miR-21 and miR-93 for predicting radiotherapy and chemotherapy efficacy before radiotherapy and chemotherapy was 0.894, and the AUCs of them for predicting the 3-year overall survival (OS) were 0.861 and 0.807, respectively. T stage (P < 0.05), M stage (P < 0.05), miR-21(P < 0.01), and miR-93 (P < 0.05) were independent risk factors for radiotherapy and chemotherapy efficacy, and T stage (P < 0.01), N stage (P < 0.05), M stage (P < 0.01), miR-21 (P < 0.01), and miR-93 (P < 0.01) were independent prognostic factors for ESCC patients.
CONCLUSION MiR-21 and miR-93 can be adopted as effective biomarkers for predicting radiotherapy and chemotherapy efficacy in ESCC and the 3-year OS of ESCC patients.
Collapse
Affiliation(s)
- Wen-Tao Wang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Chang-Qing Guo
- Digestive Department, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Guang-Hui Cui
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Song Zhao
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| |
Collapse
|
36
|
Identification of Cell-Free Circulating MicroRNAs for the Detection of Early Breast Cancer and Molecular Subtyping. JOURNAL OF ONCOLOGY 2019; 2019:8393769. [PMID: 31485228 PMCID: PMC6702831 DOI: 10.1155/2019/8393769] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 04/15/2019] [Accepted: 06/19/2019] [Indexed: 01/21/2023]
Abstract
Early detection is crucial for achieving a reduction in breast cancer mortality. Analysis of circulating cell-free microRNAs present in the serum of cancer patients has emerged as a promising new noninvasive biomarker for early detection of tumors and for predicting their molecular classifications. The rationale for this study was to identify subtype-specific molecular profiles of cell-free microRNAs for early detection of breast cancer in serum. Fifty-four early-stage breast cancers with 27 age-matched controls were selected for circulating microRNAs evaluation in the serum. The 54 cases were molecularly classified (luminal A, luminal B, luminal B Her2 positive, Her-2, triple negative). NanoString platform was used for digital detection and quantitation of 800 tagged microRNA probes and comparing the overall differences in serum microRNA expression from breast cancer cases with controls. We identified the 42 most significant (P ≤ 0.05, 1.5-fold) differentially expressed circulating microRNAs in each molecular subtype for further study. Of these microRNAs, 19 were significantly differentially expressed in patients presenting with luminal A, eight in the luminal B, ten in luminal B HER 2 positive, and four in the HER2 enriched subtype. AUC is high with suitable sensitivity and specificity. For the triple negative subtype miR-25-3p had the best accuracy. Predictive analysis of the mRNA targets suggests they encode proteins involved in molecular pathways such as cell adhesion, migration, and proliferation. This study identified subtype-specific molecular profiles of cell-free microRNAs suitable for early detection of breast cancer selected by comparison to the microRNA profile in serum for female controls without apparent risk of breast cancer. This molecular profile should be validated using larger cohort studies to confirm the potential of these miRNA for future use as early detection biomarkers that could avoid unnecessary biopsy in patients with a suspicion of breast cancer.
Collapse
|
37
|
Abstract
PURPOSE OF REVIEW Both conventional and novel approaches to early detection of ovarian cancer are reviewed in the context of new developments in our understanding of ovarian cancer biology. RECENT FINDINGS While CA125 as a single value lacks adequate specificity or sensitivity for screening, large studies have shown that a 2-stage strategy which tracks CA125 change over time and prompts transvaginal ultrasound (TVS) for a small subset of women with abnormally rising biomarker values achieves adequate specificity and detects a higher fraction of early-stage disease. Sensitivity could clearly be improved in both blood tests and in imaging. Metastasis can occur from ovarian cancers too small to increase blood levels of protein antigens and a significant fraction of ovarian cancers arise from the fimbriae of fallopian tubes that cannot be imaged with TVS. Autoantibodies, miRNA, ctDNA, DNA methylation in blood, and cervical mucus might improve sensitivity of the initial phase and magnetic relaxometry and autofluorescence could improve imaging in the second phase. Enhancing the sensitivity of two-stage strategies for early detection could reduce mortality from ovarian cancer.
Collapse
Affiliation(s)
- Denise R Nebgen
- Division of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Karen H Lu
- Division of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Robert C Bast
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
| |
Collapse
|
38
|
Bahmanpour Z, Sheervalilou R, Choupani J, Shekari Khaniani M, Montazeri V, Mansoori Derakhshan S. A new insight on serum microRNA expression as novel biomarkers in breast cancer patients. J Cell Physiol 2019; 234:19199-19211. [PMID: 31026062 DOI: 10.1002/jcp.28656] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 02/17/2019] [Accepted: 03/19/2019] [Indexed: 12/26/2022]
Abstract
Breast cancer (BC) is one of the widespread lethal diseases affecting a large number of women worldwide. As such, employing and identifying significant markers for detecting BC in different stages can assist in better diagnosis and management of the disease. Several diverse markers have been introduced for diagnosis, but their limitations, including low specificity and sensitivity, reduce their application. microRNAs (miRNAs), as short noncoding RNAs, have been shown to significantly influence gene expression in different disease pathologies, especially BC. Clearly, among different samples used for detecting miRNA expressions, circulating miRNAs present as promising and useful biomarkers. Among different body fluid samples, serum serves as one of the most reliable samples, thanks to its high stability under various severe conditions and some unique features. Extensive research has suggested that BC-related miRNAs can remain stable in the serum. The objective of this review is to describe different samples used for detecting miRNAs in BC subjects with emphasis on serum miRNAs. So, this study highlights serum miRNAs with the potential of acting as biomarkers for different stages of BC. We reviewed the possible correlation between potential miRNAs and the risk of early breast cancer, metastatic breast cancer, response to chemotherapy, and relapse.
Collapse
Affiliation(s)
- Zahra Bahmanpour
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roghayeh Sheervalilou
- Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jalal Choupani
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahmoud Shekari Khaniani
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahid Montazeri
- Department of Pathology, Imam Khomeini Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sima Mansoori Derakhshan
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
39
|
Dual-SERS biosensor for one-step detection of microRNAs in exosome and residual plasma of blood samples for diagnosing pancreatic cancer. Biosens Bioelectron 2019; 130:204-213. [DOI: 10.1016/j.bios.2019.01.039] [Citation(s) in RCA: 143] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 01/07/2019] [Accepted: 01/20/2019] [Indexed: 12/19/2022]
|
40
|
Huang Z, Chen W, Du Y, Guo Q, Mao Y, Zhou X, Hua D. Serum miR-16 as a potential biomarker for human cancer diagnosis: results from a large-scale population. J Cancer Res Clin Oncol 2019; 145:787-796. [PMID: 30706130 DOI: 10.1007/s00432-019-02849-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Accepted: 01/20/2019] [Indexed: 01/10/2023]
Abstract
BACKGROUND Cancer is a serious public health problem worldwide, and difficulty in early diagnosis has been the chief obstacle to improve the prognosis of patients. Recently, microRNAs (miRNAs) were widely studied to be potential biomarkers for cancer detection. miR-16 is a prevalent but sophisticated one. In the current study, we aimed to assess the diagnostic value of serum miR-16 for cancer detection. METHODS A total of 1458 cancer patients, containing ten types of cancers, and 1457 non-cancer controls were recruited in this study. qRT-PCR was used for the amplification of miRNAs. In addition, a meta-analysis of reported studies was performed to confirm our findings systematically. RESULTS Consequently, miR-16 was down-regulated in ESCC, GCA and GNCA patients compared with NCs (all P < 0.001), while up-regulated in PDAC patients (P = 0.001), LAC, LSCC and EEC patients (all P < 0.001). But no significant differences were observed in CRC, EOC and TC patients when compared to NCs (P = 0.747, 0.235 and 0.268, respectively). The areas under the receiver operating characteristic (ROC) curve of miR-16 in GCA, ESCC, LAC, LSCC, GNCA, PDAC and EEC were 0.881, 0.780, 0.757, 0.693, 0.602, 0.614 and 0.681, respectively. Results of meta-analysis showed that miR-16 achieved an overall pooled sensitivity of 0.72, specificity of 0.79, and AUC of 0.85, suggesting that miR-16 was a promising biomarker in cancer detection. CONCLUSIONS We provided a comprehensive view of the diagnostic value of serum miR-16 in cancer diagnosis, and confirmed that circulating miR-16 could play an important role in cancer detection.
Collapse
Affiliation(s)
- Zebo Huang
- Department of Oncology, The Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi, 214062, China
| | - Wenjiao Chen
- Department of Oncology, The Affiliated Yixing Hospital of Jiangsu University, 75 Tongzhenguan Road, Wuxi, 214200, China
| | - Yiping Du
- Department of Oncology, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, 215300, China
| | - Qin Guo
- Department of Clinical Laboratory, The Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi, 214062, China
| | - Yong Mao
- Department of Oncology, The Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi, 214062, China
| | - Xin Zhou
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
| | - Dong Hua
- Department of Oncology, The Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi, 214062, China.
| |
Collapse
|
41
|
MicroRNA in Lung Cancer Metastasis. Cancers (Basel) 2019; 11:cancers11020265. [PMID: 30813457 PMCID: PMC6406837 DOI: 10.3390/cancers11020265] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 02/17/2019] [Accepted: 02/18/2019] [Indexed: 12/12/2022] Open
Abstract
Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including invasion, migration, angiogenesis, and epithelial-to-mesenchymal transition that are tightly controlled by various genetic expression modalities along with interaction between cancer cells and the extracellular matrix. In particular, microRNAs (miRNAs), a group of small non-coding RNAs, can influence the transcriptional and post-transcriptional processes, with dysregulation of miRNA expression contributing to the regulation of cancer metastasis. Nevertheless, although miRNA-targeted therapy is widely studied in vitro and in vivo, this strategy currently affords limited feasibility and a few miRNA-targeted therapies for lung cancer have entered into clinical trials to date. Advances in understanding the molecular mechanism of metastasis will thus provide additional potential targets for lung cancer treatment. This review discusses the current research related to the role of miRNAs in lung cancer invasion and metastasis, with a particular focus on the different metastatic lesions and potential miRNA-targeted treatments for lung cancer with the expectation that further exploration of miRNA-targeted therapy may establish a new spectrum of lung cancer treatments.
Collapse
|
42
|
Small Non-Coding RNAs Derived From Eukaryotic Ribosomal RNA. Noncoding RNA 2019; 5:ncrna5010016. [PMID: 30720712 PMCID: PMC6468398 DOI: 10.3390/ncrna5010016] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 01/24/2019] [Accepted: 01/27/2019] [Indexed: 12/13/2022] Open
Abstract
The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will present a nonexhaustive list of referenced small non-coding RNAs (ncRNAs) derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs). We will focus on the rRFs that are experimentally verified, and discuss their origin, length, structure, biogenesis, association with known regulatory proteins, and potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences-because of their overabundance-from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because no one could believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.
Collapse
|
43
|
Boriachek K, Umer M, Islam MN, Gopalan V, Lam AK, Nguyen NT, Shiddiky MJA. An amplification-free electrochemical detection of exosomal miRNA-21 in serum samples. Analyst 2019; 143:1662-1669. [PMID: 29512659 DOI: 10.1039/c7an01843f] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Recent evidence suggests that small non-coding RNAs such as microRNA (miRNA) encapsulated in exosomes represent an important mechanism of communication between the cells. Exosomal miRNAs play an important role in carcinogenesis via enhancing the cell to cell communication and targeting the cell growth molecular pathways which in turn facilitate metastasis in cancers. Despite progressive advances, the current methods for the exosomal miRNA detection mostly rely on labor-intensive sequencing approaches which are often prone to amplification bias and require costly and bulky equipment. Herein, we report an electrochemical approach for the detection of cancer-derived exosomal miRNAs in human serum samples by selectively isolating the target miRNA using magnetic beads pre-functionalized with capture probes and then directly adsorbing the targets onto a gold electrode surface. The level of adsorbed miRNA is detected electrochemically in the presence of an [Fe(CN)6]4-/3- redox system. This method enabled an excellent detection sensitivity of 1.0 pM with a relative standard deviation (%RSD) of <5.5% in cancer cells and serum samples (n = 8) collected from patients with colorectal adenocarcinoma (CRC). We believe that our approach could be useful in clinical settings for the quantification of exosomal miRNA in cancer patients.
Collapse
Affiliation(s)
- Kseniia Boriachek
- School of Environment and Science, Griffith University, Nathan Campus, QLD 4111, Australia.
| | | | | | | | | | | | | |
Collapse
|
44
|
Min L, Chen L, Liu S, Yu Y, Guo Q, Li P, Zhu S. Loss of Circulating Exosomal miR-92b is a Novel Biomarker of Colorectal Cancer at Early Stage. Int J Med Sci 2019; 16:1231-1237. [PMID: 31588188 PMCID: PMC6775270 DOI: 10.7150/ijms.34540] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 07/05/2019] [Indexed: 02/06/2023] Open
Abstract
Early diagnosis of colorectal cancer (CRC) is clinically critical but technically challenging, especially in a minimal-invasive way. Emerging evidence suggests that exosome-encapsulated microRNAs (miRNAs) is a kind of promising cancer biomarker. Here we investigated the predictive potential of exosomal miR-92b in plasma samples obtained from 114 participants [40 CRC, 22 colorectal adenomas (CA), 52 non-neoplasm controls (NC)] by RT-qPCR. We found that exosomal miR-92b level was significantly down-regulated in CRC patients compared with CA and NC patients, especially in CRC at stage II, regardless of lymph node metastasis and invasive depth. The AUC in distinguishing CRC, CA and NC from each other ranged from 0.631 to 0.793, while a higher AUC of 0.830 was achieved in differentiating CRC at clinical stage II/III from NC individuals. Additionally, a logistic model integrating miR-92b with age showed a significantly improved accuracy in distinguishing CRC patients from NC (AUC increased from 0.793 to 0.867). Taken together, our findings indicated that decreased expression of exosome-derived miR-92b in plasma is a promising biomarker for early detection of CRC.
Collapse
Affiliation(s)
- Li Min
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease. No.95, Yong'an Rd, Xicheng District, Beijing,100050, P. R. China
| | - Lei Chen
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease. No.95, Yong'an Rd, Xicheng District, Beijing,100050, P. R. China
| | - Si Liu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease. No.95, Yong'an Rd, Xicheng District, Beijing,100050, P. R. China
| | - Yang Yu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease. No.95, Yong'an Rd, Xicheng District, Beijing,100050, P. R. China
| | - Qingdong Guo
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease. No.95, Yong'an Rd, Xicheng District, Beijing,100050, P. R. China
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease. No.95, Yong'an Rd, Xicheng District, Beijing,100050, P. R. China
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease. No.95, Yong'an Rd, Xicheng District, Beijing,100050, P. R. China
| |
Collapse
|
45
|
Feng L, Jing L, Han J, Wang G, Liu Y, Zhang X, Wang Y, Wang F, Ma H, Liu Y. MicroRNA 486-3p directly targets BIK and regulates apoptosis and invasion in colorectal cancer cells. Onco Targets Ther 2018; 11:8791-8801. [PMID: 30584337 PMCID: PMC6287550 DOI: 10.2147/ott.s180354] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background MicroRNAs influence almost every genetic pathway and are involved in colorectal cancer (CRC). However, the biological role of miR486-3p in CRC remains to be elucidated. Methods In this study, miR486-3p expression in CRC cell lines and normal colonic epithelial cells was determined. After miR486-3p mimic, inhibitor, and BIK siRNA transfection, cell proliferation, apoptosis, and migration were examined. Furthermore, the target of miR486-3p was identified by luciferase-reporter assay and underlying molecular mechanisms studied. Results The results revealed that miR486-3p was significantly upregulated in CRC compared with normal colonic epithelial cells, whereas BIK expression was remarkably downregulated in CRC cells. MTT assays demonstrated that suppression of miR486-3p expression reduced CRC cell proliferation, whereas elevated miR486-3p or BIK silencing induced cell proliferation. Wound-healing assays and transwell experiments revealed that both upregulation of miR486-3p and down-regulation of BIK increased CRC cell migration and invasion ability. Moreover, bioinformatic target prediction identified BIK as a putative target of miR486-3p. Knockdown of miR486-3p was shown to upregulate BIK expression, whereas overexpression of miR486-3p suppressed the expression of BIK. Luciferase reporter assay results further confirmed this deduction. Conclusion In conclusion, these findings suggest that miR486-3p is an oncogene in CRC. Gene therapy using miR486-3p inhibition may provide a new clue for CRC therapy.
Collapse
Affiliation(s)
- Li Feng
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China,
| | - Li Jing
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China,
| | - Jing Han
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China,
| | - Guiying Wang
- Second Department of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Yan Liu
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China,
| | - Xue Zhang
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China,
| | - Yudong Wang
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China,
| | - Feifei Wang
- Second Department of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Hongqing Ma
- Second Department of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Yibing Liu
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China,
| |
Collapse
|
46
|
Imani S, Wu RC, Fu J. MicroRNA-34 family in breast cancer: from research to therapeutic potential. J Cancer 2018; 9:3765-3775. [PMID: 30405848 PMCID: PMC6216011 DOI: 10.7150/jca.25576] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 08/03/2018] [Indexed: 12/25/2022] Open
Abstract
MicroRNA (miRNA)-34 family (miR-34s), including miR-34a/b/c, is the most well studied non-coding RNAs that regulate gene expression post-transcriptionally. The miR-34s mediates the tumor suppressor function of p53 in the pathogenesis of breast cancer by targeting different oncogenes. This review focuses on the anti-oncogenic regulation of the miR-34s, emphasizing the major signaling pathways that are involved in the modulation of miR-34s in breast cancer. Moreover, it highlights how epigenetic modification by the p53/miR-34s axis regulates the proliferation, invasiveness, chemoresistance, and sternness of breast cancer. A better understanding of the molecular mechanisms of miR-34s will open new opportunities for the development of novel therapeutic strategies and define a new approach in identifying potential biomarkers for early diagnosis of breast cancer.
Collapse
Affiliation(s)
- Saber Imani
- Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Ray-Chang Wu
- Department of Biochemistry and Molecular Medicine, the George Washington University, Washington, DC 20052, USA
| | - Junjiang Fu
- Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| |
Collapse
|
47
|
Zhao G, Jiang T, Liu Y, Huai G, Lan C, Li G, Jia G, Wang K, Yang M. Droplet digital PCR-based circulating microRNA detection serve as a promising diagnostic method for gastric cancer. BMC Cancer 2018; 18:676. [PMID: 29929476 PMCID: PMC6013872 DOI: 10.1186/s12885-018-4601-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 06/15/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Novel non-invasive biomarkers for gastric cancer (GC) are needed, because the present diagnostic methods for GC are either invasive or insensitive and non-specific in clinic. The presence of stable circulating microRNAs (miRNAs) in plasma suggested a promising role as GC biomarkers. METHODS Based on the quantitative droplet digital PCR (ddPCR), four miRNAs (miR-21, miR-93, miR-106a and miR-106b) related to the presence of GC were identified in plasma from a training cohort of 147 participants and a validation cohort of 28 participants. RESULTS All circulating miRNA levels were significantly higher in the plasma of GC patients compared to healthy controls (P < 0.05). Through a combination of four miRNAs by logistic regression model, receiver operating characteristic (ROC) analyses yielded the highest AUC value of 0.887 in discriminating GC patients from healthy volunteers. Furthermore, miR-21, miR-93 and miR-106b levels were significantly related to an advanced TNM stage in GC patients. ROC analyses of the combined miRNA panel also showed the highest AUC value of 0.809 in discriminating GC patients with TNM stage I and II from stage III and IV. Through combining four miRNAs and clinical parameters, a classical random forest model was established in the training stage. In the validation cohort, it correctly discriminated 23 out of 28 samples in the blinded phase (false rate, 17.8%). CONCLUSIONS Using the ddPCR technique, circulating miR-21, miR-93, miR-106a and miR-106b could be used as diagnostic plasma biomarkers in gastric cancer patients.
Collapse
Affiliation(s)
- Gaoping Zhao
- Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China. .,School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China. .,Institute of Chengdu Biology, and Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, 610041, China.
| | - Tao Jiang
- Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China.,School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Yanzhuo Liu
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Guoli Huai
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Chunbin Lan
- Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China.,School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Guiquan Li
- Department of General Surgery, Qionglai Medical Center Hospital, Chengdu, Sichuan Province, China, Chengdu, 611530, China
| | - Guiqing Jia
- Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China.,School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Kang Wang
- Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China.,School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Maozhu Yang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China. .,Institute of Chengdu Biology, and Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, 610041, China. .,Department of General Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China.
| |
Collapse
|
48
|
Guelfi G, Cochetti G, Stefanetti V, Zampini D, Diverio S, Boni A, Mearini E. Next Generation Sequencing of urine exfoliated cells: an approach of prostate cancer microRNAs research. Sci Rep 2018; 8:7111. [PMID: 29740090 PMCID: PMC5940782 DOI: 10.1038/s41598-018-24236-y] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 03/22/2018] [Indexed: 12/24/2022] Open
Abstract
There is emerging evidence that microRNAs (miRNAs) dysregulation is involved in the genesis and the progression of Prostate Cancer (PCa), thus potentially increasing their use in urological clinical practice. This is the first pilot study which utilizes Illumina Deep Sequencing to examine the entire miRNAs spectrum existent in urine exfoliated prostate cells (UEPCs) of PCa patients. A total of 11 male patients with histological diagnosis of PCa were enrolled in the present study. First-catch urine (30 mL) was collected following a prostate massage. Total RNA was extracted from urine and sequenced using an HiSeq2500 System (Illumina). QPCR assay was used to validate the highest NGS results in PCA patients and in age-matched, caucasian men. Remarkably, PCA let-7 family was down-regulated (P < 0.01), compared to the controls. The results of our study support the notion of a relatively high diagnostic value of miRNA family for PCa detection, especially in the let-7 family. The present research confirmed the potential use of miRNAs as non-invasive biomarkers in the diagnosis of PCa, potentially reducing the invasiveness of actual clinical strategy.
Collapse
Affiliation(s)
- Gabriella Guelfi
- Department of Veterinary Medicine, University of Perugia, Via S. Costanzo n.4, 06126, Perugia, PG, Italy.
| | - Giovanni Cochetti
- Department of Surgical and Biomedical Sciences, Section of Urological, Andrological and Minimally invasive techniques, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, PG, Italy
| | - Valentina Stefanetti
- Department of Veterinary Medicine, University of Perugia, Via S. Costanzo n.4, 06126, Perugia, PG, Italy
| | - Danilo Zampini
- Department of Veterinary Medicine, University of Perugia, Via S. Costanzo n.4, 06126, Perugia, PG, Italy
| | - Silvana Diverio
- Department of Veterinary Medicine, University of Perugia, Via S. Costanzo n.4, 06126, Perugia, PG, Italy
| | - Andrea Boni
- Department of Surgical and Biomedical Sciences, Section of Urological, Andrological and Minimally invasive techniques, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, PG, Italy
| | - Ettore Mearini
- Department of Surgical and Biomedical Sciences, Section of Urological, Andrological and Minimally invasive techniques, University of Perugia, Piazza Lucio Severi 1, 06132, Perugia, PG, Italy
| |
Collapse
|
49
|
Potential Role of MicroRNA-375 as Biomarker in Human Cancers Detection: A Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2017; 2017:1875843. [PMID: 29259977 PMCID: PMC5702930 DOI: 10.1155/2017/1875843] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 09/10/2017] [Indexed: 12/31/2022]
Abstract
The association between circulating microRNA-375 (miR-375) expression and cancers has been studied; however, the results are inconsistent. We searched PubMed, Embase, and Web of Science for studies concerning the diagnostic value of miR-375 for cancer. The bivariate meta-analysis model was employed to summarize sensitivity, specificity, and diagnostic odds ratio (DOR) for miR-375 in the diagnosis of cancer. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were also used to check the overall test performance. A total of 645 cancer patients and 421 cancer-free individuals from 12 studies were contained in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 78% (95% confidence interval (CI): 64%-87%), the specificity was 74% (95% CI: 62%-84%), the DOR was 10.04 (95% CI: 6.01-16.77), and the AUC was 0.82 (95% CI: 0.79-0.85). In addition, we found that the diagnostic effect of miR-375 varies according to the race and cancer type. Our data suggest that miR-375 profiling has a potential to be used as a screening test for cancers but the specific race and cancer should be considered. More studies on the diagnostic value of miR-375 for cancer are needed in the future.
Collapse
|
50
|
Kuznetsov VA, Tang Z, Ivshina AV. Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets. BMC Genomics 2017; 18:692. [PMID: 28984201 PMCID: PMC5629558 DOI: 10.1186/s12864-017-4027-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background High-grade serous ovarian carcinoma (HG-SOC) is the dominant tumor histologic type in epithelial ovarian cancers, exhibiting highly aberrant microRNA expression profiles and diverse pathways that collectively determine the disease aggressiveness and clinical outcomes. However, the functional relationships between microRNAs, the common pathways controlled by the microRNAs and their prognostic and therapeutic significance remain poorly understood. Methods We investigated the gene expression patterns of microRNAs in the tumors of 582 HG-SOC patients to identify prognosis signatures and pathways controlled by tumor miRNAs. We developed a variable selection and prognostic method, which performs a robust selection of small-sized subsets of the predictive features (e.g., expressed microRNAs) that collectively serves as the biomarkers of cancer risk and progression stratification system, interconnecting these features with common cancer-related pathways. Results Across different cohorts, our meta-analysis revealed two robust and unbiased miRNA-based prognostic classifiers. Each classifier reproducibly discriminates HG-SOC patients into high-confidence low-, intermediate- or high-prognostic risk subgroups with essentially different 5-year overall survival rates of 51.6-85%, 20-38.1%, and 0-10%, respectively. Significant correlations of the risk subgroup’s stratification with chemotherapy treatment response were observed. We predicted specific target genes involved in nine cancer-related and two oocyte maturation pathways (neurotrophin and progesterone-mediated oocyte maturation), where each gene can be controlled by more than one miRNA species of the distinct miRNA HG-SOC prognostic classifiers. Conclusions We identified robust and reproducible miRNA-based prognostic subsets of the of HG-SOC classifiers. The miRNAs of these classifiers could control nine oncogenic and two developmental pathways, highlighting common underlying pathologic mechanisms and perspective targets for the further development of a personalized prognosis assay(s) and the development of miRNA-interconnected pathway-centric and multi-agent therapeutic intervention. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-4027-5) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Vladimir A Kuznetsov
- Genome and Gene Expression Data Analysis Division, Bioinformatics Institute, A-STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore. .,School of Computer Science and Engineering, Nanyang Technological University, Singapore, 639798, Singapore.
| | - Zhiqun Tang
- Genome and Gene Expression Data Analysis Division, Bioinformatics Institute, A-STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore
| | - Anna V Ivshina
- Genome and Gene Expression Data Analysis Division, Bioinformatics Institute, A-STAR, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore
| |
Collapse
|