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Xiao J, Deng Y, Xie J, Liu H, Yang Q, Zhang Y, Huang X, Cao Z. Apoptotic vesicles from macrophages exacerbate periodontal bone resorption in periodontitis via delivering miR-143-3p targeting Igfbp5. J Nanobiotechnology 2024; 22:658. [PMID: 39456001 PMCID: PMC11515254 DOI: 10.1186/s12951-024-02934-2] [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: 07/24/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024] Open
Abstract
ABSTRCT BACKGROUND: Apoptotic vesicles (ApoVs), which are extracellular vesicles released by apoptotic cells, have been reported to exhibit substantial therapeutic potential for inflammatory diseases and tissue regeneration. While extensive research has been dedicated to mesenchymal stem cells (MSCs), the investigation into immune cell-derived ApoVs remains limited, particularly regarding the function and fate of macrophage-derived ApoVs in the context of periodontitis (PD). RESULTS Our study corroborates the occurrence and contribution of resident macrophage apoptosis in Porphyromonas gingivalis (Pg)-associated PD. The findings unveil the pivotal role played by apoptotic macrophages and their derived ApoVs in orchestrating periodontal bone remodeling. The enrichments of diverse functional miRNAs within these ApoVs are discerned through sequencing techniques. Moreover, our study elucidates that the macrophage-derived ApoVs predominantly deliver miR-143-3p, targeting insulin-like growth factor-binding protein 5 (IGFBP5), thereby disrupting periodontal bone homeostasis. CONCLUSIONS Our study reveals that macrophages in Pg-associated PD undergo apoptosis and generate miR-143-3p-enriched ApoVs to silence IGFBP5, resulting in the perturbation of osteogenic-osteoclastic balance and the ensuing periodontal bone destruction. Accordingly, interventions targeting miR-143-3p in macrophages or employment of apoptosis inhibitor Z-VAD hold promise as effective therapeutic strategies for the management of PD.
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Affiliation(s)
- Junhong Xiao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
- Qingdao Stomatological Hospital Affiliated to Qingdao University, No.17 Dexian Road, Shinan District, Qingdao, 266001, Shandong Province, China
| | - Yifei Deng
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Jirong Xie
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Heyu Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Qiudong Yang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Yufeng Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
- Medical Research Institute, School of Medicine, Wuhan University, Wuhan, 430071, China.
- Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Hongshan District, Wuhan, 430079, China.
| | - Xin Huang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
- Department of Periodontology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Hongshan District, Wuhan, 430079, China.
| | - Zhengguo Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
- Department of Periodontology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Hongshan District, Wuhan, 430079, China.
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Rajput S, Malviya R, Uniyal P. Advancements in the diagnosis, prognosis, and treatment of retinoblastoma. CANADIAN JOURNAL OF OPHTHALMOLOGY 2024; 59:281-299. [PMID: 38369298 DOI: 10.1016/j.jcjo.2024.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 12/05/2023] [Accepted: 01/29/2024] [Indexed: 02/20/2024]
Abstract
Retinoblastoma (RB) is a prevalent primitive intraocular malignancy in children, particularly in those younger than age 3 years. RB is caused by mutations in the RB1 gene. In developing countries, mortality rates for this type of cancer are still high, whereas industrialized countries have achieved a survival rate of >95%-98%. Untreated, the condition can be fatal, underscoring the importance of early diagnosis. The existing treatments primarily consist of surgery, radiotherapy, and chemotherapy. The detrimental effects of radiation and chemotherapeutic drugs have been documented as factors that contribute to increased mortality rates and negatively affect the quality of life for patients. MicroRNA (miRNA), a type of noncoding RNA, exerts a substantial influence on RB development and the emergence of treatment resistance by regulating diverse cellular processes. This review highlights recent developments in the involvement of miRNAs in RB. This encompasses the clinical significance of miRNAs in the diagnosis, prognosis, and treatment of RB. Additionally, this paper examines the regulatory mechanisms of miRNAs in RB and explores potential therapeutic interventions. This paper provides an overview of the current and emerging treatment options for RB, focusing on recent studies investigating the application of different types of nanoparticles for the diagnosis and treatment of this condition.
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Affiliation(s)
- Shivam Rajput
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India.
| | - Prerna Uniyal
- School of Pharmacy, Graphic Era Hill University, Dehradun, India
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Stefańska K, Volponi AA, Kulus M, Waśko J, Farzaneh M, Grzelak J, Azizidoost S, Mozdziak P, Bukowska D, Antosik P, Zabel M, Podhorska-Okołów M, Dzięgiel P, Szcześniak M, Woszczyk M, Kempisty B. Dental pulp stem cells - A basic research and future application in regenerative medicine. Biomed Pharmacother 2024; 178:116990. [PMID: 39024839 DOI: 10.1016/j.biopha.2024.116990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/10/2024] [Accepted: 06/15/2024] [Indexed: 07/20/2024] Open
Abstract
Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.
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Affiliation(s)
- Katarzyna Stefańska
- Cellivia 3 S.A., Poznan 60-529, Poland; Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan 60-781, Poland.
| | - Ana Angelova Volponi
- Centre for Craniofacial and Regenerative Biology, Dental Institute, King's College London, London WC2R 2LS, UK.
| | - Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | | | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Joanna Grzelak
- Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Shirin Azizidoost
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Paul Mozdziak
- Prestage Department of Poultry Sciences, North Carolina State University, Raleigh, NC 27695, USA.
| | - Dorota Bukowska
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | - Paweł Antosik
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | - Maciej Zabel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland; Division of Anatomy and Histology, University of Zielona Góra, Zielona Góra 65-046, Poland.
| | - Marzenna Podhorska-Okołów
- Division of Ultrastructural Research, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Marta Szcześniak
- Department of Diagnostics, Poznan University of Medical Sciences, Bukowska 70, Poznań 60-812, Poland; Department of Maxillofacial Surgery, Poznan University of Medical Sciences, Przybyszewskiego 49, Poznań 60-355, Poland.
| | | | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland; Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland; College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695, USA; Center of Assisted Reproduction, Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Brno, Czech Republic
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Chi Y, Liu T, Jin Q, Liu H. Extracellular Vesicles Carrying RUNX3 Promote Differentiation of Dental Pulp Stem Cells. Tissue Eng Regen Med 2024; 21:111-122. [PMID: 37684540 PMCID: PMC10764680 DOI: 10.1007/s13770-023-00578-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/07/2023] [Accepted: 07/11/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND This study aims to clarify the mechanism underlying dental pulp cells-extracellular vesicles (DPC-EVs) carrying runt-related transcription factor 3 (RUNX3) in mediating odontogenic differentiation of dental pulp stem cells (DPSCs) with the involvement of miR-30a-5p-regulated NOTCH1. METHODS Extracellular vesicles (EVs) were isolated from human DPSCs, and identified using transmission electron microscopy, and nanoparticle tracking analysis. PBS, EVs, or EV inhibitor GW4869 was added to DPSCs for co-culture, whilst odontogenic differentiation was assessed in terms of ratio of mineralized nodules and expression odontoblast differentiation markers. Dual luciferase reporter gene assay and chromatin immunoprecipitation for binding relation among RUNX3, miR-30a-5p and NOTCH1were employed to evaluate their roles in odontogenic differentiation was determined. Animal experiment was established to confirm the effect of DPC-EVs-loaded RUNX3 on dental pulp. RESULTS In vitro finding demonstrated that EVs delivered RUNX3 to DPSCs, thereby activated miR-30a-5p expression and inhibited NOTCH1 expression, which was reversed by addition of GW4869. RUNX3 upregulation promoted miR-30a-5p while miR-30a-5p targeted and inhibited NOTCH1. Silencing of RUNX3 in EVs decreased expression of those differentiation markers, downregulated miR-30a-5p and upregulated NOTCH1. CONCLUSION DPSC-EVs can carry RUNX3 to the DPSCs, promote the transcription of miR-30a-5p, and then inhibit the expression of NOTCH1, and finally promote the odontogenic differentiation of DPSCs.
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Affiliation(s)
- Yuhong Chi
- Department of Stomatology, The People's Hospital of Suzhou New District, 16-502, Dongbang Xinyuan, Fengqiao Street, Huqiu District, Suzhou, Jiangsu Province, People's Republic of China
| | - Tingzhong Liu
- Department of Stomatology, The People's Hospital of Suzhou New District, 16-502, Dongbang Xinyuan, Fengqiao Street, Huqiu District, Suzhou, Jiangsu Province, People's Republic of China
| | - Qingsong Jin
- Department of Oral and Maxillofacial Surgery, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar, People's Republic of China
| | - Hao Liu
- Department of Stomatology, The People's Hospital of Suzhou New District, 16-502, Dongbang Xinyuan, Fengqiao Street, Huqiu District, Suzhou, Jiangsu Province, People's Republic of China.
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Doghish AS, Moustafa HAM, Elballal MS, Sarhan OM, Darwish SF, Elkalla WS, Mohammed OA, Atta AM, Abdelmaksoud NM, El-Mahdy HA, Ismail A, Abdel Mageed SS, Elrebehy MA, Abdelfatah AM, Abulsoud AI. miRNAs as potential game-changers in retinoblastoma: Future clinical and medicinal uses. Pathol Res Pract 2023; 247:154537. [PMID: 37216745 DOI: 10.1016/j.prp.2023.154537] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 05/10/2023] [Accepted: 05/16/2023] [Indexed: 05/24/2023]
Abstract
Retinoblastoma (RB) is a rare tumor in children, but it is the most common primitive intraocular malignancy in childhood age, especially those below three years old. The RB gene (RB1) undergoes mutations in individuals with RB. Although mortality rates remain high in developing countries, the survival rate for this type of cancer is greater than 95-98% in industrialized countries. However, it is lethal if left untreated, so early diagnosis is essential. As a non-coding RNA, miRNA significantly impacts RB development and treatment resistance because it can control various cellular functions. In this review, we illustrate the recent advances in the role of miRNAs in RB. That includes the clinical importance of miRNAs in RB diagnosis, prognosis, and treatment. Moreover, the regulatory mechanisms of miRNAs in RB and therapeutic interventions are discussed.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt.
| | - Hebatallah Ahmed Mohamed Moustafa
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Omnia M Sarhan
- Department of Pharmaceutics, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Samar F Darwish
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Wagiha S Elkalla
- Microbiology and Immunology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Osama A Mohammed
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt; Department of Clinical Pharmacology, Faculty of Medicine, Bisha University, Bisha 61922, Saudi Arabia
| | - Asmaa M Atta
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | | | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt.
| | - Ahmed Ismail
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo 11829, Egypt
| | - Amr M Abdelfatah
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Badr University in Cairo, Badr, Cairo 11829, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr, Cairo 11231, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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Soheilifar MH, Nobari S, Hakimi M, Adel B, Masoudi-Khoram N, Reyhani E, Neghab HK. Current concepts of microRNA-mediated regulatory mechanisms in human pulp tissue-derived stem cells: a snapshot in the regenerative dentistry. Cell Tissue Res 2023:10.1007/s00441-023-03792-4. [PMID: 37247032 DOI: 10.1007/s00441-023-03792-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 05/12/2023] [Indexed: 05/30/2023]
Abstract
One of the most studied class of non-coding RNAs is microRNAs (miRNAs) which regulate more than 60% of human genes. A network of miRNA gene interactions participates in stem cell self-renewal, proliferation, migration, apoptosis, immunomodulation, and differentiation. Human pulp tissue-derived stem cells (PSCs) are an attractive source of dental mesenchymal stem cells (MSCs) which comprise human dental pulp stem cells (hDPSCs) obtained from the dental pulp of permanent teeth and stem cells isolated from exfoliated deciduous teeth (SHEDs) that would be a therapeutic opportunity in stomatognathic system reconstruction and repair of other damaged tissues. The regenerative capacity of hDPSCs and SHEDs is mediated by osteogenic, odontogenic, myogenic, neurogenic, angiogenic differentiation, and immunomodulatory function. Multi-lineage differentiation of PSCs can be induced or inhibited by the interaction of miRNAs with their target genes. Manipulating the expression of functional miRNAs in PSCs by mimicking miRNAs or inhibiting miRNAs emerged as a therapeutic tool in the clinical translation. However, the effectiveness and safety of miRNA-based therapeutics, besides higher stability, biocompatibility, less off-target effects, and immunologic reactions, have received particular attention. This review aimed to comprehensively overview the molecular mechanisms underlying miRNA-modified PSCs as a futuristic therapeutic option in regenerative dentistry.
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Affiliation(s)
| | - Sima Nobari
- Research Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Hakimi
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Bashir Adel
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
| | - Nastaran Masoudi-Khoram
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Elahe Reyhani
- Faculty of Dentistry, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hoda Keshmiri Neghab
- Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
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Iranmanesh P, Vedaei A, Salehi-Mazandarani S, Nikpour P, Khazaei S, Khademi A, Galler KM, Nekoofar MH, Dummer PMH. MicroRNAs-mediated regulation of the differentiation of dental pulp-derived mesenchymal stem cells: a systematic review and bioinformatic analysis. Stem Cell Res Ther 2023; 14:76. [PMID: 37038220 PMCID: PMC10088330 DOI: 10.1186/s13287-023-03289-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 03/16/2023] [Indexed: 04/12/2023] Open
Abstract
BACKGROUND Human dental pulp-derived mesenchymal stem cells (hDP-MSCs), which include human dental pulp stem cells (hDPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs), are promising cell sources for regenerative therapies. Nevertheless, a lack of knowledge relating to the mechanisms regulating their differentiation has limited their clinical application. microRNAs (miRNAs) are important regulatory molecules in cellular processes including cell differentiation. This systematic review aims to provide a panel of miRNAs that regulate the differentiation of hDP-MSCs including hDPSCs and SHEDs. Additionally, bioinformatic analyses were conducted to discover target genes, signaling pathways and gene ontologies associated with the identified miRNAs. METHODS A literature search was performed in MEDLINE (via PubMed), Web of Science, Scopus, Embase and Cochrane Library. Experimental studies assessing the promotive/suppressive effect of miRNAs on the differentiation of hDP-MSCs and studies evaluating changes to the expression of miRNAs during the differentiation of hDP-MSCs were included. miRNAs involved in odontogenic/osteogenic differentiation were then included in a bioinformatic analysis. A miRNA-mRNA network was constructed, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. A protein-protein interaction (PPI) network was also constructed. RESULTS Of 766 initially identified records through database searching, 42 and 36 studies were included in qualitative synthesis and bioinformatic analyses, respectively. Thirteen miRNAs promoted and 17 suppressed odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-140-5p, hsa-miR-218 and hsa-miR-143 were more frequently reported suppressing the odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-221 and hsa-miR-124 promoted and hsa-miR-140-5p inhibited neuronal differentiation, hsa-miR-26a-5p promoted and hsa-miR-424 suppressed angiogenic differentiation, and hsa-miR-135 and hsa-miR-143 inhibited differentiation within myogenic lineages. A miRNA-mRNA network including 1890 nodes and 2171 edges was constructed. KEGG pathway analysis revealed MAPK, PI3K-Akt and FoxO as key signaling pathways involved in the odontogenic/osteogenic differentiation of hDP-MSCs. CONCLUSIONS The findings of this systematic review support the potential application of the specific miRNAs to regulate the directed differentiation of hDP-MSCs in the field of regenerative therapies.
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Affiliation(s)
- Pedram Iranmanesh
- Dental Research Center, Department of Endodontics, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirhossein Vedaei
- Student Research Committee, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sadra Salehi-Mazandarani
- Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Parvaneh Nikpour
- Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Saber Khazaei
- Department of Endodontics, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Abbasali Khademi
- Dental Research Center, Department of Endodontics, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kerstin M. Galler
- Department of Conservative Dentistry and Periodontology, University Hospital Erlangen, Erlangen, Germany
| | - Mohammad-Hossein Nekoofar
- Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Department of Endodontics, Bahçeşehir University School of Dentistry, Istanbul, Turkey
| | - Paul M. H. Dummer
- School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
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Liu P, Li Y, Wang W, Bai Y, Jia H, Yuan Z, Yang Z. Role and mechanisms of the NF-ĸB signaling pathway in various developmental processes. Biomed Pharmacother 2022; 153:113513. [DOI: 10.1016/j.biopha.2022.113513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/26/2022] [Accepted: 08/01/2022] [Indexed: 11/02/2022] Open
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Kalaimani L, Devarajan B, Namperumalsamy VP, Veerappan M, Daniels JT, Chidambaranathan GP. Hsa-miR-143-3p inhibits Wnt-β-catenin and MAPK signaling in human corneal epithelial stem cells. Sci Rep 2022; 12:11432. [PMID: 35794158 PMCID: PMC9259643 DOI: 10.1038/s41598-022-15263-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 06/21/2022] [Indexed: 11/09/2022] Open
Abstract
Our previous study demonstrated hsa-miR-143-3p as one of the highly expressed miRNAs in enriched corneal epithelial stem cells (CESCs). Hence this study aims to elucidate the regulatory role of hsa-miR-143-3p in the maintenance of stemness in CESCs. The target genes of hsa-miR-143-3p were predicted and subjected to pathway analysis to select the targets for functional studies. Primary cultured limbal epithelial cells were transfected with hsa-miR-143-3p mimic, inhibitor or scrambled sequence using Lipofectamine 3000. The transfected cells were analysed for (i) colony forming potential, (ii) expression of stem cell (SC) markers/ transcription factors (ABCG2, NANOG, OCT4, KLF4, ΔNp63), (iii) differentiation marker (Cx43), (iv) predicted five targets of hsa-miR-143-3p (DVL3, MAPK1, MAPK14, KRAS and KAT6A), (v) MAPK signaling regulators and (vi) Wnt-β-catenin signaling regulators by qPCR, immunofluorescence staining and/or Western blotting. High expression of hsa-miR-143-3p increased the colony forming potential (10.04 ± 1.35%, p < 0.001) with the ability to form holoclone-like colonies in comparison to control (3.33 ± 0.71%). The mimic treated cells had increased expression of SC markers but reduced expression of Cx43 and hsa-miR-143-3p targets involved in Wnt-β-catenin and MAPK signaling pathways. The expression of β-catenin, active β-catenin and ERK2 in hsa-miR-143-3p inhibitor transfected cells were higher than the control cells and the localized nuclear expression indicated the activation of Wnt and MAPK signaling. Thus, the probable association of hsa-miR-143-3p in the maintenance of CESCs through inhibition of Wnt and MAPK signaling pathways was thus indicated.
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Affiliation(s)
- Lavanya Kalaimani
- Department of Immunology and Stem Cell Biology, Aravind Medical Research Foundation, Madurai, Tamil Nadu, 625020, India.,Department of Biotechnology, Aravind Medical Research Foundation-Affiliated to Alagappa University, Karaikudi, Tamil Nadu, India.,Institute of Ophthalmology, University College London, London, UK
| | - Bharanidharan Devarajan
- Department of Bioinformatics, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India
| | | | - Muthukkaruppan Veerappan
- Department of Immunology and Stem Cell Biology, Aravind Medical Research Foundation, Madurai, Tamil Nadu, 625020, India
| | - Julie T Daniels
- Institute of Ophthalmology, University College London, London, UK
| | - Gowri Priya Chidambaranathan
- Department of Immunology and Stem Cell Biology, Aravind Medical Research Foundation, Madurai, Tamil Nadu, 625020, India. .,Department of Biotechnology, Aravind Medical Research Foundation-Affiliated to Alagappa University, Karaikudi, Tamil Nadu, India.
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Zhang W, Yuan X. MicroRNA-20a elevates osteogenic/odontoblastic differentiation potential of dental pulp stem cells by nuclear factor-κB/p65 signaling pathway via targeting interleukin-8. Arch Oral Biol 2022; 138:105414. [DOI: 10.1016/j.archoralbio.2022.105414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 03/21/2022] [Accepted: 03/21/2022] [Indexed: 11/26/2022]
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Zeng B, Huang J. Progress in the Study of Non-Coding RNAs in Multidifferentiation Potential of Dental-Derived Mesenchymal Stem Cells. Front Genet 2022; 13:854285. [PMID: 35480302 PMCID: PMC9037064 DOI: 10.3389/fgene.2022.854285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/17/2022] [Indexed: 12/28/2022] Open
Abstract
For decades, the desire for tissue regeneration has never been quenched. Dental-derived mesenchymal stem cells (DMSCs), with the potential of self-renewal and multi-directional differentiation, have attracted much attention in this topic. Growing evidence suggests that non-coding RNAs (ncRNAs) can activate various regulatory processes. Even with a slight decrease or increase in expression, ncRNAs can weaken or even subvert cellular fate. Therefore, a systematic interpretation of ncRNAs that guide the differentiation of DMSCs into cells of other tissue types is urgently needed. In this review, we introduce the roles of ncRNAs in the differentiation of DMSCs, such as osteogenic differentiation, odontogenic differentiation, neurogenic differentiation, angiogenic differentiation and myogenic differentiation. Additionally, we illustrate the regulatory mechanisms of ncRNAs in the differentiation of DMSCs, such as epigenetic regulation, transcriptional regulation, mRNA modulation, miRNA sponges and signalling. Finally, we summarize the types and mechanisms of ncRNAs in the differentiation of DMSCs, such as let-7 family, miR-17∼92 family, miR-21, lncRNA H19, lncRNA ANCR, lncRNA MEG3, circRNA CDR1as and CircRNA SIPA1L1. If revealing the intricate relationship between ncRNAs and pluripotency of DMSCs 1 day, the application of DMSCs in regenerative medicine and tissue engineering will be improved. Our work could be an important stepping stone towards this future.
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Affiliation(s)
- Biyun Zeng
- Department of Oral Pathology, Xiangya Stomatological Hospital & Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha, China
| | - Junhui Huang
- Department of Oral Pathology, Xiangya Stomatological Hospital & Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha, China
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Gao S, Ge LH, Zhao YM, Li P, Li YY, Zhao W. Hsa-miRNA-143-3p regulates the odontogenic differentiation of human stem cells from the apical papilla by targeting NFIC. Int Endod J 2022; 55:263-274. [PMID: 34807471 DOI: 10.1111/iej.13666] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 01/01/2023]
Abstract
AIM To evaluate the effects of hsa-miRNA-143-3p on the cytodifferentiation of human stem cells from the apical papilla (hSCAPs) and the post-transcriptional regulation of Nuclear factor I-C (NFIC). METHODOLOGY miRNA expression profiles in human immature permanent teeth and during hSCAP differentiation were examined. hSCAPs were treated with miR-143-3p overexpression or silencing viruses, and the proliferation and odontogenic and osteogenic differentiation of these stem cells, and the involvement of the NFIC pathway, were investigated. Luciferase reporter and NFIC mutant plasmids were used to confirm NFIC mRNA as a direct target of miR-143-3p. NFIC expression analysis in the miR-143-3p overexpressing hSCAPs was used to investigate whether miR-143-3p functioned by targeting NFIC. Student's t-test and chi-square tests were used for statistical analysis. RESULTS miR-143-3p expression was screened by microarray profiling and was found to be significantly reduced during hSCAP differentiation (p < .05). Overexpression of miR-143-3p inhibited the mineralization of hSCAPs significantly (p < .05) and downregulated the levels of odontogenic differentiation markers (NFIC [p < .05], DSP [p < .01] and KLF4 [p < .01]), whereas silencing of miR-143-3p had the opposite effect. The luciferase reporter gene detection and bioinformatic approaches identified NFIC mRNA as a potential target of miR-143-3p. NFIC overexpression reversed the inhibitory effect of miR-143-3p on the odontogenic differentiation of hSCAPs. CONCLUSIONS miR-143-3p maintained the stemness of hSCAPs and modulated their differentiation negatively by directly targeting NFIC. Thus, inhibition of this miRNA represents a potential strategy to promote the regeneration of damaged tooth roots.
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Affiliation(s)
- Shuo Gao
- Department of Pediatric Dentistry, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China
| | - Li-Hong Ge
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Peking University Health Science Center, Peking University, Beijing, China
| | - Yu-Ming Zhao
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Peking University Health Science Center, Peking University, Beijing, China
| | - Pei Li
- Department of Pediatric Dentistry, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China
| | - Yao-Yin Li
- Department of Pediatric Dentistry, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China
| | - Wei Zhao
- Department of Pediatric Dentistry, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China
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13
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miR-143-3p Inhibits the Differentiation of Osteoclast Induced by Synovial Fibroblast and Monocyte Coculture in Adjuvant-Induced Arthritic Rats. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5565973. [PMID: 34485516 PMCID: PMC8416385 DOI: 10.1155/2021/5565973] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 08/03/2021] [Accepted: 08/14/2021] [Indexed: 12/03/2022]
Abstract
Osteoclast, which mediates overactive bone resorption, is one of the key factors for bone destruction in rheumatoid arthritis (RA). Existing studies have shown that abnormal miR-143-3p expression was observed in both RA patients and arthritis animals, which can participate in osteoclast differentiation, and mitogen-activated protein kinase (MAPK) signaling pathway was closely related to osteoclast differentiation. The primary objective of the current study was to determine the role of miR-143-3p in the progression of osteoclast differentiation and its relationship with MAPK signaling pathways. The results showed that miR-143-3p inhibited osteoclast differentiation and decreased the levels of M-CSF and RANKL during osteoclast differentiation. miR-143-3p inhibited the expression of MAPK signaling proteins, which is ERK1/2 in the early stage and JNK in the later stage of osteoclast differentiation. It was also observed that MAPK inhibitors upregulated miR-143-3p expression in osteoclast differentiation. Taken together, our results suggested that miR-143-3p could inhibit the differentiation of osteoclast, which was related to inhibiting MAPK signaling pathways. This may provide a novel strategy for curing RA.
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Yin JY, Luo XH, Feng WQ, Miao SH, Ning TT, Lei Q, Jiang T, Ma DD. Multidifferentiation potential of dental-derived stem cells. World J Stem Cells 2021; 13:342-365. [PMID: 34136070 PMCID: PMC8176842 DOI: 10.4252/wjsc.v13.i5.342] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/10/2021] [Accepted: 04/05/2021] [Indexed: 02/06/2023] Open
Abstract
Tooth-related diseases and tooth loss are widespread and are a major public health issue. The loss of teeth can affect chewing, speech, appearance and even psychology. Therefore, the science of tooth regeneration has emerged, and attention has focused on tooth regeneration based on the principles of tooth development and stem cells combined with tissue engineering technology. As undifferentiated stem cells in normal tooth tissues, dental mesenchymal stem cells (DMSCs), which are a desirable source of autologous stem cells, play a significant role in tooth regeneration. Researchers hope to reconstruct the complete tooth tissues with normal functions and vascularization by utilizing the odontogenic differentiation potential of DMSCs. Moreover, DMSCs also have the ability to differentiate towards cells of other tissue types due to their multipotency. This review focuses on the multipotential capacity of DMSCs to differentiate into various tissues, such as bone, cartilage, tendon, vessels, neural tissues, muscle-like tissues, hepatic-like tissues, eye tissues and glands and the influence of various regulatory factors, such as non-coding RNAs, signaling pathways, inflammation, aging and exosomes, on the odontogenic/osteogenic differentiation of DMSCs in tooth regeneration. The application of DMSCs in regenerative medicine and tissue engineering will be improved if the differentiation characteristics of DMSCs can be fully utilized, and the factors that regulate their differentiation can be well controlled.
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Affiliation(s)
- Jing-Yao Yin
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Xing-Hong Luo
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Wei-Qing Feng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Sheng-Hong Miao
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Ting-Ting Ning
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Qian Lei
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Tao Jiang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Dan-Dan Ma
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
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Wangzhou K, Lai Z, Lu Z, Fu W, Liu C, Liang Z, Tan Y, Li C, Hao C. MiR-143-3p Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Targeting KLF5 and Inactivating the Wnt/β-Catenin Pathway. Front Physiol 2021; 11:606967. [PMID: 33603676 PMCID: PMC7884451 DOI: 10.3389/fphys.2020.606967] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 12/18/2020] [Indexed: 11/13/2022] Open
Abstract
Human periodontal ligament cells (hPDLCs) play a vital role in cell regeneration and tissue repair with multi-directional differentiation potential. microRNAs (miRs) are implicated in the osteogenesis of hPDLCs. This study explored the mechanism of miR-143-3p in osteogenesis of hPDLCs. Osteogenic differentiation of isolated hPDLCs was induced. KLF5 expression during osteogenic differentiation of hPDLCs was detected and then silenced in hPDLCs. Binding relationship between KLF5 and miR-143-3p was predicted and verified. hPDLCs were treated with miR-143-3p mimic or overexpressing KLF5, and then osteogenic specific markers and mineralized nodules were measured. The key factors of the Wnt/β-catenin pathway during osteogenesis of hPDLCs were measured. KLF5 expression was upregulated during osteogenesis of hPDLCs. KLF5 silencing or miR-143-3p mimic reduced osteogenic specific markers and mineralized nodules. Overexpression of KLF5 could reverse the inhibitory effect of miR-143-3p on osteogenic differentiation. miR-143-3p mimic and KLF5 silencing inactivated the Wnt/β-catenin pathway. Activation of the Wnt/β-catenin pathway reversed the repression effect of miR-143-3p mimic on osteogenesis of hPDLCs. In conclusion, miR-143-3p inhibited osteogenic differentiation of hPDLCs by targeting KLF5 and inactivating the Wnt/β-catenin pathway.
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Affiliation(s)
- Kaixin Wangzhou
- School of Management, Hainan Medical University, Haikou, China
| | - Zhiying Lai
- College of Stomatology, Hainan Medical University, Haikou, China
| | - Zishao Lu
- College of Stomatology, Hainan Medical University, Haikou, China
| | - Wanren Fu
- College of Stomatology, Hainan Medical University, Haikou, China
| | - Cheng Liu
- Department of Stomatology, Harbin Stomatological Hospital, Harbin, China
| | - Zhengeng Liang
- Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yi Tan
- Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Conghui Li
- Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Chunbo Hao
- Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
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Wu L, Song J, Xue J, Xiao T, Wei Q, Zhang Z, Zhang Y, Li Z, Hu Y, Zhang G, Xia H, Li J, Yang X, Liu Q. MircoRNA-143-3p regulating ARL6 is involved in the cadmium-induced inhibition of osteogenic differentiation in human bone marrow mesenchymal stem cells. Toxicol Lett 2020; 331:159-166. [DOI: 10.1016/j.toxlet.2020.06.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 04/16/2020] [Accepted: 06/03/2020] [Indexed: 12/20/2022]
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circRNA Expression Profile in Dental Pulp Stem Cells during Odontogenic Differentiation. Stem Cells Int 2020; 2020:5405931. [PMID: 32952566 PMCID: PMC7482017 DOI: 10.1155/2020/5405931] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 06/25/2020] [Accepted: 08/08/2020] [Indexed: 12/11/2022] Open
Abstract
Introduction Odontogenic differentiation of human dental pulp stem cells (hDPSCs) is a key step of pulp regeneration. Recent studies showed that circular RNAs (circRNAs) have many biological functions and that competing endogenous RNA (ceRNA) is their most common mechanism of action. However, the role of circRNAs in hDPSCs during odontogenesis is still unclear. Methods Isolated hDPSCs were cultured in essential and odontogenic medium. Total RNA was extracted after 14 days of culture, and then, microarray analysis was performed to measure the differential expressions of circRNAs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was then performed to validate the microarray results. Based on microarray data from this study and available in the database, a ceRNA network was constructed to investigate the potential function of circRNAs during odontogenesis. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential correlation between signaling pathways and circRNAs. In addition, qRT-PCR and Western blot analysis were used to explore the function of hsa_circRNA_104101. Results We found 43 upregulated circRNAs and 144 downregulated circRNAs during the odontogenic differentiation process (fold change > 1.5 and <-1.5, respectively; P < 0.05). qRT-PCR results were in agreement with the microarray results. Bioinformatic analysis revealed that the Wnt signaling pathway and the TGF-β signaling pathway, as well as the other pathways associated with odontogenic differentiation, were correlated to the differentially expressed circRNAs. hsa_circRNA_104101 was proved to promote the odontogenic differentiation of hDPSCs. Conclusion This study reported 187 circRNAs that were differentially expressed in hDPSCs during odontogenic differentiation. Bioinformatic analysis of the expression data suggested that circRNA-miRNA-mRNA networks might act as a crucial mechanism for hDPSC odontogenic differentiation, providing a theoretical foundation for the study of pulp regeneration regulation by circRNAs.
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Zheng Q, Zhu Q, Li C, Hao S, Li J, Yu X, Qi D, Pan Y. microRNA-144 functions as a diagnostic and prognostic marker for retinoblastoma. Clinics (Sao Paulo) 2020; 75:e1804. [PMID: 32844953 PMCID: PMC7426600 DOI: 10.6061/clinics/2020/e1804] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 05/19/2020] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES Retinoblastoma (RB) is a highly malignant eye tumor with a low survival rate and a high metastatic rate. The current work was designed to investigate the potential roles of microRNA-144 (miR-144) in the diagnosis and prognosis of RB. METHODS miR-144 expression levels in RB tissues and adjacent normal tissues, as well as serum samples from RB patients and healthy controls were measured. The association between miR-144 expression levels and clinical features were analyzed. Moreover, diagnostic and prognostic values of miR-144 in RB were verified by receiver operating characteristic analysis and Kaplan-Meier survival assays. RESULTS The expression level of miR-144 was markedly decreased in tumor tissues of RB patients, and the expression level of miR-144 was positively associated with tumor size and metastasis in RB patients. Moreover, miR-144 can distinguish tumor tissues from normal tissues with high specificity and sensitivity, and RB patients with lower miR-144 expression have shorter overall and disease-free survival rates than those with higher miR-144 expression. Alternatively, miR-144 also decreased in the serum of RB patients in comparison with healthy subjects, and miR-144 expression levels in the tissue samples and serum were positively correlated. Furthermore, miR-144 levels in the serum of RB patients sensitively distinguished RB patients from healthy controls. CONCLUSIONS miR-144 expression was downregulated in serum and tissue samples of RB patients and may function as a diagnostic and prognostic marker for RB.
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Affiliation(s)
| | | | | | | | | | | | | | - Yu Pan
- *Corresponding author. E-mail:
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