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Shukla D, Mishra S, Mandal T, Charan M, Verma AK, Khan MMA, Chatterjee N, Dixit AK, Ganesan SK, Ganju RK, Srivastava AK. MicroRNA-379-5p attenuates cancer stem cells and reduces cisplatin resistance in ovarian cancer by regulating RAD18/Polη axis. Cell Death Dis 2025; 16:140. [PMID: 40016217 PMCID: PMC11868536 DOI: 10.1038/s41419-025-07430-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 01/22/2025] [Accepted: 02/05/2025] [Indexed: 03/01/2025]
Abstract
Ovarian cancer (OC) is an aggressive malignancy of the female reproductive organs, associated with a low 5-year survival rate. Emerging evidence suggests the pivotal role of microRNAs (miRNAs) in regulating chemoresistance and metastasis in OC, primarily through cancer stem cells (CSCs), also known as cancer stem-like cells (CSLCs). Herein, we demonstrate that miR-379-5p is downregulated in several OC cell populations including both cell lines and patient tumor samples. Furthermore, overexpression of miR-379-5p effectively inhibits CSCs and counteracts cisplatin-induced expansion of CSCs. Further mechanistic investigations identify RAD18, a DNA repair protein involved in translesion DNA synthesis (TLS), as a direct target of miR-379-5p. Moreover, a negative correlation between miR-379-5p and RAD18 expression is observed in ovarian CSCs isolated from OC patients. The downregulation of RAD18 inhibits stem-like phenotypes and enhances the sensitivity of ovarian CSCs to cisplatin treatment. Importantly, miR-379-5p-mediated inhibition of RAD18 prevents the repair synthesis in CSCs by promoting the accumulation of DNA damage. In vivo studies further reveal that miR-379-5p enhances DNA damage, which, in turn, inhibits tumor cell proliferation in athymic nude mice. Remarkably, targeting of RAD18 by miR-379-5p prevents monoubiquitination of proliferating cell nuclear antigen (PCNA), resulting in reduced DNA Polymerase η (a TLS polymerase that helps to bypass DNA lesions) recruitment to lesion sites. In the absence of Polη, the persisting DNA lesions cause activation of cell cycle arrest and apoptosis pathway in CSCs. Therefore, our findings unveil a novel mechanism whereby miR-379-5p overexpression curtails CSCs by modulating the RAD18/Polη axis.
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Affiliation(s)
- Devendra Shukla
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Sanjay Mishra
- Department of Pathology, The Ohio State University, Columbus, OH, USA
| | - Tanima Mandal
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Manish Charan
- Department of Pathology, The Ohio State University, Columbus, OH, USA
| | - Ajeet Kumar Verma
- Department of Pathology, The Ohio State University, Columbus, OH, USA
| | - Md Maqsood Ahamad Khan
- Structural Biology & Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India
| | | | | | - Senthil Kumar Ganesan
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
- Structural Biology & Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India
| | - Ramesh K Ganju
- Department of Pathology, The Ohio State University, Columbus, OH, USA.
| | - Amit Kumar Srivastava
- Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.
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Hu X, Lei X, Lin W, Li X, Zhong W, Luo B, Xie J, Liang Z, Li Y, Qiu J, Wang P, Zhu X, Zhang R, Yang L. Quercetin promotes osteogenic differentiation of bone marrow mesenchymal stem cells by modulating the miR-214-3p/Wnt3a/β-catenin signaling pathway. Exp Cell Res 2025; 444:114386. [PMID: 39694404 DOI: 10.1016/j.yexcr.2024.114386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 12/12/2024] [Accepted: 12/15/2024] [Indexed: 12/20/2024]
Abstract
Postmenopausal osteoporosis, primarily driven by estrogen deficiency, is predominantly mediated through estrogen receptors such as ERα. However, the underlying mechanisms necessitate further investigation. In this study, we established an ERα-deficient model in rBMSCs to elucidate the role of ERα in osteogenic differentiation and miRNA expression profiles. Our findings demonstrate that knockdown of ERα inhibits osteogenic differentiation in rBMSCs, resulting in upregulation of 25 miRNAs and downregulation of 184 miRNAs, including a significant increase in the expression of miR-214-3p. Validation using qPCR, Western blotting, and bioinformatics analysis revealed that miR-214-3p negatively regulates osteogenic differentiation via the Wnt/β-catenin signaling pathway. Furthermore, we explored the potential therapeutic effects of quercetin (QUE) on rBMSCs. CCK8, alkaline phosphatase activity assays, and Alizarin Red staining demonstrated that QUE dose-dependently enhances rBMSCs proliferation, alkaline phosphatase activity, and mineralization within the concentration range of 0.1-1 μM. Importantly, QUE was found to downregulate miR-214-3p expression and activate the Wnt3a/β-catenin signaling pathway. Rescue experiments confirmed that QUE could counteract the inhibitory effects of miR-214-3p on the Wnt3a/β-catenin signaling pathway. Collectively, our study provides compelling evidence that knockdown of ERα inhibits the osteogenic differentiation of rBMSCs by affecting the miRNA expression profile, while QUE can reverse the inhibitory effect exerted by miR-214-3p on the Wnt3a/β-catenin signaling pathway, thereby offering novel insights into diagnosis, prevention, and treatment strategies for postmenopausal osteoporosis.
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Affiliation(s)
- Xueling Hu
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Xiaotong Lei
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Weiwen Lin
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Xiaoyun Li
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Wenqiang Zhong
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Bingjie Luo
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Ji Xie
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Ziwen Liang
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Yunchuan Li
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Jingli Qiu
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China
| | - Panpan Wang
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China; College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China
| | - Xiaofeng Zhu
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China; College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China
| | - Ronghua Zhang
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China.
| | - Li Yang
- College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, 510632, China.
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Bharti, Nair MS. Targeting Human Papillomavirus 33 E2 DNA Binding Domain With Polyphenols: Unveiling Interactions Through Biophysical and In Silico Methods. J Mol Recognit 2025; 38:e3106. [PMID: 39396813 DOI: 10.1002/jmr.3106] [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: 05/18/2024] [Revised: 09/04/2024] [Accepted: 09/09/2024] [Indexed: 10/15/2024]
Abstract
The human papillomavirus (HPV) 33 is a high-risk strain that causes lesions with potential cancerous outcomes. Its E2 protein regulates the viral protein transcription and life cycle maintenance. The DNA binding domain (DBD) of the E2 protein plays a crucial role in the viral life cycle. The DBD region of the E2 protein is particularly interesting for targeting and finding potential inhibitors to inhibit its function or dimerization. Given the limited research on HPV 33 and its proteins, the present work delved into the interaction of two natural polyphenolic compounds, resveratrol, and baicalein, with the E2 DBD of HPV 33 using biophysical and in silico studies. Fluorescence studies of the E2 DBD-polyphenol complexes showed fluorescence quenching with a binding constant of the order of 106 M-1. Circular dichroism data reveal conformational changes upon binding with the polyphenols, possibly due to distinct binding sites of the E2 DBD. Differential scanning calorimetry exhibited higher melting temperatures for the two complexes than alone DBD, suggesting the complexes' stability. ITC experiment suggested favorable binding reactions with k d values in the micromolar range. Molecular docking and dynamic simulation studies revealed that the resveratrol binds to the helical region and baicalein near the central dimeric interface of E2 DBD with a good binding affinity, forming a stable protein-ligand complex during the run of 100 ns simulation. Therefore, the current study identifies both polyphenolic compounds as promising candidates for potential antiviral drug development.
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Affiliation(s)
- Bharti
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, India
| | - Maya S Nair
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, India
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Zhang A, Lu L, Yang F, Luo T, Yang S, Yang P, Li X, Deng X, Qiu Y, Chen L, Long K, Pan D, Jin L, Li M, Chen L. Effects of miR-29c on proliferation and adipogenic differentiation of porcine bone marrow mesenchymal stromal cells. Adipocyte 2024; 13:2365211. [PMID: 38858810 PMCID: PMC11174058 DOI: 10.1080/21623945.2024.2365211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 05/24/2024] [Indexed: 06/12/2024] Open
Abstract
microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.
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Affiliation(s)
- Anjing Zhang
- Department of Pig Production, Chongqing Academy of Animal Science, Chongqing, China
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Lu Lu
- Department of Pig Production, Chongqing Academy of Animal Science, Chongqing, China
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
- College of Animal Science and Technology, Southwest University, Chongqing, China
| | - Fuxing Yang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Tingting Luo
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Shuqi Yang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Peidong Yang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Xuemin Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Xiaoli Deng
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Yang Qiu
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Litong Chen
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Keren Long
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Dengke Pan
- Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, China
| | - Long Jin
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Mingzhou Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Li Chen
- Department of Pig Production, Chongqing Academy of Animal Science, Chongqing, China
- Key Laboratory of Animal Resource Evaluation and Utilization (Pigs), Ministry of Agriculture and Rural Affairs, Chongqing, China
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Kazimierczyk M, Fedoruk-Wyszomirska A, Gurda-Woźna D, Wyszko E, Swiatkowska A, Wrzesinski J. The expression profiles of piRNAs and their interacting Piwi proteins in cellular model of renal development: Focus on Piwil1 in mitosis. Eur J Cell Biol 2024; 103:151444. [PMID: 39024988 DOI: 10.1016/j.ejcb.2024.151444] [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: 02/02/2024] [Revised: 07/03/2024] [Accepted: 07/12/2024] [Indexed: 07/20/2024] Open
Abstract
Piwi proteins and Piwi interacting RNAs, piRNAs, presented in germline cells play a role in transposon silencing during germline development. In contrast, the role of somatic Piwi proteins and piRNAs still remains obscure. Here, we characterize the expression pattern and distribution of piRNAs in human renal cells in terms of their potential role in kidney development. Further, we show that all PIWI genes are expressed at the RNA level, however, only PIWIL1 gene is detected at the protein level by western blotting in healthy and cancerous renal cells. So far, the expression of human Piwil1 protein has only been shown in testes and cancer cells, but not in healthy somatic cell lines. Since we observe only Piwil1 protein, the regulation of other PIWI genes is probably more intricated, and depends on environmental conditions. Next, we demonstrate that downregulation of Piwil1 protein results in a decrease in the rate of cell proliferation, while no change in the level of apoptotic cells is observed. Confocal microscopy analysis reveals that Piwil1 protein is located in both cellular compartments, cytoplasm and nucleus in renal cells. Interestingly, in nucleus region Piwil1 is observed close to the spindle during all phases of mitosis in all tested cell lines. It strongly indicates that Piwil1 protein plays an essential role in proliferation of somatic cells. Moreover, involvement of Piwil1 in cell division could, at least partly, explain invasion and metastasis of many types of cancer cells with upregulation of PIWIL1 gene expression. It also makes Piwil1 protein as a potential target in the anticancer therapy.
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Affiliation(s)
- Marek Kazimierczyk
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan 61-704, Poland
| | | | - Dorota Gurda-Woźna
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan 61-704, Poland
| | - Eliza Wyszko
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan 61-704, Poland
| | - Agata Swiatkowska
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan 61-704, Poland.
| | - Jan Wrzesinski
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan 61-704, Poland.
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Duan W, Shen Q, Ju L, Huang Z, Geng J, Wu Q, Yu C, Wei J. Homologous Tumor Cell-Derived Biomimetic Nano-Trojan Horse Integrating Chemotherapy with Genetherapy for Boosting Triple-Negative Breast Cancer Therapy. ACS APPLIED MATERIALS & INTERFACES 2024; 16:45523-45536. [PMID: 39141925 DOI: 10.1021/acsami.4c08842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that carries the worst prognosis and lacks specific therapeutic targets. To achieve accurate "cargos" delivery at the TNBC site, we herein constructed a novel biomimetic nano-Trojan horse integrating chemotherapy with gene therapy for boosting TNBC treatment. Briefly, we initially introduce the diselenide-bond-containing organosilica moieties into the framework of mesoporous silica nanoparticles (MONs), thereby conferring biodegradability to intratumoral redox conditions in the obtained MONSe. Subsequently, doxorubicin (Dox) and therapeutic miR-34a are loaded into MONSe, thus achieving the combination of chemotherapy and gene-therapy. After homologous tumor cell membrane coating, the ultimate homologous tumor cell-derived biomimetic nano-Trojan horse (namely, MONSe@Dox@miR-34a@CM) can selectively enter the tumor cells in a stealth-like fashion. Notably, such a nanoplatform not only synergistically eradicated the tumor but also inhibited the proliferation of breast cancer stem-like cells (BCSCs) in vitro and in vivo. With the integration of homologous tumor cell membrane-facilitated intratumoral accumulation, excellent biodegradability, and synergistic gene-chemotherapy, our biomimetic nanocarriers hold tremendous promise for the cure of TNBC in the future.
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Affiliation(s)
- Wenjie Duan
- Department of Pharmacy, Jiangsu Cancer Hospital, the Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, 42 Baiziting Road, Nanjing 210009, China
| | - Qian Shen
- Key Laboratory of Flexible Electronics (KLOFE), School of Flexible Electronics (Future Technologies) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China
| | - Linjie Ju
- Department of Pharmacy, Jiangsu Cancer Hospital, the Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, 42 Baiziting Road, Nanjing 210009, China
| | - Zhongxi Huang
- Key Laboratory of Flexible Electronics (KLOFE), School of Flexible Electronics (Future Technologies) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China
| | - Jiaying Geng
- Key Laboratory of Flexible Electronics (KLOFE), School of Flexible Electronics (Future Technologies) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China
| | - Qiong Wu
- Key Laboratory of Flexible Electronics (KLOFE), School of Flexible Electronics (Future Technologies) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China
| | - Changmin Yu
- Key Laboratory of Flexible Electronics (KLOFE), School of Flexible Electronics (Future Technologies) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China
| | - Jifu Wei
- Department of Pharmacy, Jiangsu Cancer Hospital, the Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, 42 Baiziting Road, Nanjing 210009, China
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Ordóñez-Rubiano EG, Rincón-Arias N, Espinosa S, Shelton WJ, Salazar AF, Cómbita A, Baldoncini M, Luzzi S, Payán-Gómez C, Gómez- Amarillo DF, Hakim F, Patiño-Gómez JG, Parra- Medina R. The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2024; 7:100193. [PMID: 39055532 PMCID: PMC11268206 DOI: 10.1016/j.crphar.2024.100193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/29/2024] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
Glioblastoma (GBM) is the most common malignant central nervous system tumor. The emerging field of epigenetics stands out as particularly promising. Notably, the discovery of micro RNAs (miRNAs) has paved the way for advancements in diagnosing, treating, and prognosticating patients with brain tumors. We aim to provide an overview of the emergence of miRNAs in GBM and their potential role in the multifaceted management of this disease. We discuss the current state of the art regarding miRNAs and GBM. We performed a narrative review using the MEDLINE/PUBMED database to retrieve peer-reviewed articles related to the use of miRNA approaches for the treatment of GBMs. MiRNAs are intrinsic non-coding RNA molecules that regulate gene expression mainly through post-transcriptional mechanisms. The deregulation of some of these molecules is related to the pathogenesis of GBM. The inclusion of molecular characterization for the diagnosis of brain tumors and the advent of less-invasive diagnostic methods such as liquid biopsies, highlights the potential of these molecules as biomarkers for guiding the management of brain tumors such as GBM. Importantly, there is a need for more studies to better examine the application of these novel molecules. The constantly changing characterization and approach to the diagnosis and management of brain tumors broaden the possibilities for the molecular inclusion of novel epigenetic molecules, such as miRNAs, for a better understanding of this disease.
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Affiliation(s)
- Edgar G. Ordóñez-Rubiano
- School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia
- Department of Neurosurgery, Fundación Universitaria de Ciencias de La Salud, Hospital de San José – Sociedad de Cirugía de Bogotá, Bogotá D.C., Colombia
- Department of Neurosurgery, Fundación Santa Fe de Bogotá, Bogotá, Colombia
| | - Nicolás Rincón-Arias
- Department of Neurosurgery, Fundación Universitaria de Ciencias de La Salud, Hospital de San José – Sociedad de Cirugía de Bogotá, Bogotá D.C., Colombia
| | - Sebastian Espinosa
- Department of Neurosurgery, Fundación Universitaria de Ciencias de La Salud, Hospital de San José – Sociedad de Cirugía de Bogotá, Bogotá D.C., Colombia
| | | | | | - Alba Cómbita
- School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia
- Department of Microbiology, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Matías Baldoncini
- School of Medicine, Laboratory of Microsurgical Neuroanatomy, Second Chair of Gross Anatomy, University of Buenos Aires, Buenos Aires, Argentina
- Department of Neurological Surgery, Hospital San Fernando, Buenos Aires, Argentina
| | - Sabino Luzzi
- Neurosurgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - César Payán-Gómez
- Dirección Académica, Universidad Nacional de Colombia, Sede de La Paz, La Paz, Colombia
| | | | - Fernando Hakim
- Department of Neurosurgery, Fundación Santa Fe de Bogotá, Bogotá, Colombia
| | - Javier G. Patiño-Gómez
- Department of Neurosurgery, Fundación Universitaria de Ciencias de La Salud, Hospital de San José – Sociedad de Cirugía de Bogotá, Bogotá D.C., Colombia
| | - Rafael Parra- Medina
- Department of Pathology, Instituto Nacional de Cancerología, Bogotá, Colombia
- Research Institute, Fundación Universitaria de Ciencias de La Salud (FUCS), Hospital de San José – Sociedad de Cirugía de Bogotá, Bogotá, Colombia
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Dai Z, Zhan Z, Chen Y, Li J. MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway. Tob Induc Dis 2024; 22:TID-22-92. [PMID: 38813585 PMCID: PMC11135024 DOI: 10.18332/tid/186643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 11/19/2023] [Accepted: 03/29/2024] [Indexed: 05/31/2024] Open
Abstract
INTRODUCTION The aim of the study is the regulatory effect of MicroRNA-210 (MiR-210) on cigarette smoke extract (CSE)-induced mouse lung epithelial type II cells (MLE-12) apoptosis and determine whether the MiR-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via Shh signaling pathway. METHODS Expression of MiR-210 in CSE-induced MLE-12 was assessed by qRT-PCR. The emphysema mouse model and MiR-210 knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vector instillation. The Sonic hedgehog (Shh), Ptch1, Gli1, B-cell lymphoma-2 (Bcl-2), and Caspase 3 protein expressions were detected by Western blotting. mRNA expressions of MiR-210, Shh, Ptch1, and Gli1 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Apoptotic ratios in mice and CSE-induced HPVEC were assessed using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays and flow cytometry. RESULTS Our results showed that MiR-210 mRNA levels were significantly down-regulated in the CSE-induced MLE 12. MLE 12 apoptosis with down-regulated Shh, Ptch1, Gli1, and Bcl-2 expression, increased Caspase 3 expression in the emphysema mouse model and CSE-induced MLE 12. Knockdown MiR-210 can facilitate cell apoptosis and emphysema via the Shh signaling pathway in mice. In vitro, MiR-210 can attenuate the apoptosis of CSE-exposed MLE 12. Moreover, MiR-210 regulated the Shh pathway and promoted its expression. CONCLUSIONS MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway. The present study reveals that MiRNA-210 may be a key regulator of cellular apoptosis and could be explored as a potential therapeutic target in the future.
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Affiliation(s)
- Zhongshang Dai
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Zijie Zhan
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Yan Chen
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, China
- Research Unit of Respiratory Disease, Central South University, Changsha, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, China
| | - Jinhua Li
- Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, China
- Research Unit of Respiratory Disease, Central South University, Changsha, China
- Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, China
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Tahmasebi F, Asl ER, Vahidinia Z, Barati S. Stem Cell-Derived Exosomal MicroRNAs as Novel Potential Approach for Multiple Sclerosis Treatment. Cell Mol Neurobiol 2024; 44:44. [PMID: 38713302 PMCID: PMC11076329 DOI: 10.1007/s10571-024-01478-1] [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: 11/08/2023] [Accepted: 04/09/2024] [Indexed: 05/08/2024]
Abstract
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation and demyelination of CNS neurons. Up to now, there are many therapeutic strategies for MS but they are only being able to reduce progression of diseases and have not got any effect on repair and remyelination. Stem cell therapy is an appropriate method for regeneration but has limitations and problems. So recently, researches were used of exosomes that facilitate intercellular communication and transfer cell-to-cell biological information. MicroRNAs (miRNAs) are a class of short non-coding RNAs that we can used to their dysregulation in order to diseases diagnosis. The miRNAs of microvesicles obtained stem cells may change the fate of transplanted cells based on received signals of injured regions. The miRNAs existing in MSCs may be displayed the cell type and their biological activities. Current studies show also that the miRNAs create communication between stem cells and tissue-injured cells. In the present review, firstly we discuss the role of miRNAs dysregulation in MS patients and miRNAs expression by stem cells. Finally, in this study was confirmed the relationship of microRNAs involved in MS and miRNAs expressed by stem cells and interaction between them in order to find appropriate treatment methods in future for limit to disability progression.
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Affiliation(s)
- Fatemeh Tahmasebi
- Department of Anatomy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elmira Roshani Asl
- Department of Biochemistry, Saveh University of Medical Sciences, Saveh, Iran
| | - Zeinab Vahidinia
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Shirin Barati
- Department of Anatomy, Saveh University of Medical Sciences, Saveh, Iran.
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10
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Cardenas RP, Zyoud A, McIntyre A, Alberio R, Mongan NP, Allegrucci C. NANOG controls testicular germ cell tumour stemness through regulation of MIR9-2. Stem Cell Res Ther 2024; 15:128. [PMID: 38693576 PMCID: PMC11062916 DOI: 10.1186/s13287-024-03724-1] [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: 12/18/2023] [Accepted: 04/08/2024] [Indexed: 05/03/2024] Open
Abstract
BACKGROUND Testicular germ cell tumours (TGCTs) represent a clinical challenge; they are most prevalent in young individuals and are triggered by molecular mechanisms that are not fully understood. The origin of TGCTs can be traced back to primordial germ cells that fail to mature during embryonic development. These cells express high levels of pluripotency factors, including the transcription factor NANOG which is highly expressed in TGCTs. Gain or amplification of the NANOG locus is common in advanced tumours, suggesting a key role for this master regulator of pluripotency in TGCT stemness and malignancy. METHODS In this study, we analysed the expression of microRNAs (miRNAs) that are regulated by NANOG in TGCTs via integrated bioinformatic analyses of data from The Cancer Genome Atlas and NANOG chromatin immunoprecipitation in human embryonic stem cells. Through gain-of-function experiments, MIR9-2 was further investigated as a novel tumour suppressor regulated by NANOG. After transfection with MIR9-2 mimics, TGCT cells were analysed for cell proliferation, invasion, sensitivity to cisplatin, and gene expression signatures by RNA sequencing. RESULTS For the first time, we identified 86 miRNAs regulated by NANOG in TGCTs. Among these, 37 miRNAs were differentially expressed in NANOG-high tumours, and they clustered TGCTs according to their subtypes. Binding of NANOG within 2 kb upstream of the MIR9-2 locus was associated with a negative regulation. Low expression of MIR9-2 was associated with tumour progression and MIR9-2-5p was found to play a role in the control of tumour stemness. A gain of function of MIR9-2-5p was associated with reduced proliferation, invasion, and sensitivity to cisplatin in both embryonal carcinoma and seminoma tumours. MIR9-2-5p expression in TGCT cells significantly reduced the expression of genes regulating pluripotency and cell division, consistent with its functional effect on reducing cancer stemness. CONCLUSIONS This study provides new molecular insights into the role of NANOG as a key determinant of pluripotency in TGCTs through the regulation of MIR9-2-5p, a novel epigenetic modulator of cancer stemness. Our data also highlight the potential negative feedback mediated by MIR9-2-5p on NANOG expression, which could be exploited as a therapeutic strategy for the treatment of TGCTs.
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Affiliation(s)
- Ryan P Cardenas
- SVMS, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK
| | - Ahmad Zyoud
- SVMS, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK
| | - Alan McIntyre
- School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK
- Centre for Cancer Sciences and Nottingham Breast Cancer Research Centre, Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Ramiro Alberio
- School of Biosciences, Faculty of Science, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK
| | - Nigel P Mongan
- SVMS, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK
- Centre for Cancer Sciences and Nottingham Breast Cancer Research Centre, Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK
- Department of Pharmacology, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA
| | - Cinzia Allegrucci
- SVMS, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
- Centre for Cancer Sciences and Nottingham Breast Cancer Research Centre, Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK.
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11
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Marques M, Ramos B, Albuquerque H, Pereira M, Ribeiro DR, Nunes A, Sarabando J, Brás D, Ferreira AR, Vitorino R, Amorim MJ, Silva AM, Soares AR, Ribeiro D. Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregates. iScience 2024; 27:109100. [PMID: 38405606 PMCID: PMC10884513 DOI: 10.1016/j.isci.2024.109100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 12/11/2023] [Accepted: 01/30/2024] [Indexed: 02/27/2024] Open
Abstract
Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells' proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.
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Affiliation(s)
- Mariana Marques
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Bruno Ramos
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Hélio Albuquerque
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
| | - Marisa Pereira
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Diana Roberta Ribeiro
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Alexandre Nunes
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Jéssica Sarabando
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Daniela Brás
- Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal
| | - Ana Rita Ferreira
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Rui Vitorino
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Maria João Amorim
- Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal
- Católica Biomedical Research Centre, Católica Medical School, Universidade Católica Portuguesa, 1649-023 Lisboa, Portugal
| | - Artur M.S. Silva
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
| | - Ana Raquel Soares
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
| | - Daniela Ribeiro
- Institute of Biomedicine – iBiMED, Department of Medical Sciences University of Aveiro, Aveiro, Portugal
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12
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Bharti, Nair MS. Molecular cloning, biophysical and in silico studies of Human papillomavirus 33 E2 DNA binding domain. J Biomol Struct Dyn 2024:1-20. [PMID: 38385450 DOI: 10.1080/07391102.2024.2317996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 02/07/2024] [Indexed: 02/23/2024]
Abstract
Human papillomavirus 33, a high-risk HPV strain, is mainly responsible for HPV infection and cervical cancer in Asian countries. The E2 protein of HPV 33 is a DNA-binding protein that plays a crucial role in viral replication and transcription. We have cloned, overexpressed, and purified the DNA binding domain of the E2 protein. Size exclusion chromatography results suggested that the protein exists in a homodimeric state in the native form. Circular dichroism data showed that the protein has a higher content of β-sheet. The melting temperature obtained from differential scanning calorimetry is 52.59 °C, and the protein is stable at pH 8 and is in a dimeric form at basic pH. The protein is monomeric or unfolded at a very low pH. Chemical denaturation studies suggested that the protein denatured and dissociated simultaneously. The DNA binding activity of the protein was also confirmed and it showed binding affinity in the order of 106 M-1. The protein structure was modeled using homology modeling and other bioinformatic tools. The virtual screening and molecular dynamic simulation studies were performed to find compounds that can act as potent inhibitors against E2 DBD. This study expands the understanding of the conserved structural and binding properties of HPV33 E2 DBD and provides the first report on the characterization of the viral protein.
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Affiliation(s)
- Bharti
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Haridwar Uttarakhand, India
| | - Maya S Nair
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Haridwar Uttarakhand, India
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13
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Ajmeera D, Ajumeera R. Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance. Genes Dis 2024; 11:148-175. [PMID: 37588226 PMCID: PMC10425757 DOI: 10.1016/j.gendis.2022.12.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 11/21/2022] [Accepted: 12/08/2022] [Indexed: 01/21/2023] Open
Abstract
Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments. Novel strategies are therefore required for better management of cancer therapy. The prime approach would be to synthesize and develop novel drugs that need extensive resources, time, and endurance to be brought into therapeutic use. The subsequent approach would be to screen the anti-cancer activity of available non-cancerous drugs. This concept of repurposing non-cancer drugs as an alternative to current cancer therapy has become popular in recent years because using existing anticancer drugs has several adverse effects. Micronutrients have also been investigated for cancer therapy due to their significant anti-cancer effects with negligible or no side effects and availability in food sources. In this paper, we discuss an ideal hypothesis for screening available non-cancerous drugs with anticancer activity, with a focus on cancer stem cells and their clinical application for cancer treatment. Further, drug repurposing and the combination of micronutrients that can target both cancers and cancer stem cells may result in a better therapeutic approach leading to maximum tumor growth control.
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Affiliation(s)
- Divya Ajmeera
- Cell Biology Department, ICMR-National Institute of Nutrition (NIN), Hyderabad, Telangana 500007, India
| | - Rajanna Ajumeera
- Cell Biology Department, ICMR-National Institute of Nutrition (NIN), Hyderabad, Telangana 500007, India
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14
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Emami Nejad A, Mostafavi Zadeh SM, Nickho H, Sadoogh Abbasian A, Forouzan A, Ahmadlou M, Nedaeinia R, Shaverdi S, Manian M. The role of microRNAs involved in the disorder of blood-brain barrier in the pathogenesis of multiple sclerosis. Front Immunol 2023; 14:1281567. [PMID: 38193092 PMCID: PMC10773759 DOI: 10.3389/fimmu.2023.1281567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/30/2023] [Indexed: 01/10/2024] Open
Abstract
miRNAs are involved in various vital processes, including cell growth, development, apoptosis, cellular differentiation, and pathological cellular activities. Circulating miRNAs can be detected in various body fluids including serum, plasma, saliva, and urine. It is worth mentioning that miRNAs remain stable in the circulation in biological fluids and are released from membrane-bound vesicles called exosomes, which protect them from RNase activity. It has been shown that miRNAs regulate blood-brain barrier integrity by targeting both tight junction and adherens junction molecules and can also influence the expression of inflammatory cytokines. Some recent studies have examined the impact of certain commonly used drugs in Multiple Sclerosis on miRNA levels. In this review, we will focus on the recent findings on the role of miRNAs in multiple sclerosis, including their role in the cause of MS and molecular mechanisms of the disease, utilizing miRNAs as diagnostic and clinical biomarkers, using miRNAs as a therapeutic modality or target for Multiple Sclerosis and drug responses in patients, elucidating their importance as prognosticators of disease progression, and highlighting their potential as a future treatment for MS.
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Affiliation(s)
| | - Seyed Mostafa Mostafavi Zadeh
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hamid Nickho
- Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Sadoogh Abbasian
- Department of Internal Medicine, School of Medicine, Amiralmomenin Hospital, Arak University of Medical Sciences, Arak, Iran
| | - Azim Forouzan
- Department of Internal Medicine, School of Medicine, Amiralmomenin Hospital, Arak University of Medical Sciences, Arak, Iran
| | - Mojtaba Ahmadlou
- Department of Biostatistics, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Reza Nedaeinia
- Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Saham Shaverdi
- Department of Biology, Payame Noor University (PNU), Tehran, Iran
| | - Mostafa Manian
- Department of Medical Laboratory Science, Faculty of Medicine, Islamic Azad University, Kermanshah, Iran
- Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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15
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Nasiri K, Jahri M, Kolahdouz S, Soleimani M, Makiya A, Saini RS, Merza MS, Yasamineh S, Banakar M, Yazdanpanah MH. MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases. Mol Diagn Ther 2023; 27:703-722. [PMID: 37773247 DOI: 10.1007/s40291-023-00675-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2023] [Indexed: 10/01/2023]
Abstract
Undifferentiated, highly proliferative, clonogenic, and self-renewing dental stem cells have paved the way for novel approaches to mending cleft palates, rebuilding lost jawbone and periodontal tissue, and, most significantly, recreating lost teeth. New treatment techniques may be guided by a better understanding of these cells and their potential in terms of the specificity of the regenerative response. MicroRNAs have been recognized as an essential component in stem cell biology due to their role as epigenetic regulators of the processes that determine stem cell destiny. MicroRNAs have been proven to be crucial in a wide variety of molecular and biological processes, including apoptosis, cell proliferation, migration, and necrocytosis. MicroRNAs have been recognized to control protein translation, messenger RNA stability, and transcription and have been reported to play essential roles in dental stem cell biology, including the differentiation of dental stem cells, the immunological response, apoptosis, and the inflammation of the dental pulp. Because microRNAs increase dental stem cell differentiation, they may be used in regenerative medicine to either preserve the stem cell phenotype or to aid in the development of tooth tissue. The development of novel biomarkers and therapies for dental illnesses relies heavily on progress made in our knowledge of the roles played by microRNAs in regulating dental stem cells. In this article, we discuss how dental stem cells and their associated microRNAs may be used to cure dental illness.
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Affiliation(s)
- Kamyar Nasiri
- Department of Dentistry, Islamic Azad University, Tehran, Iran
| | - Mohammad Jahri
- Dental Research Center, School of Dentistry, Shahid Beheshti, Research Institute of Dental Sciences, University of Medical Sciences, Tehran, Iran
| | | | | | - Ali Makiya
- Student Research Committee, Faculty of Dentistry, Mashhad University of Medical Science, Mashhad, Iran
| | - Ravinder S Saini
- COAMS, King Khalid University, Abha, 62529, Kingdom of Saudi Arabia
| | - Muna S Merza
- Prosthetic Dental Techniques Department, Al-Mustaqbal University College, Babylon, 51001, Iraq
| | - Saman Yasamineh
- Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Morteza Banakar
- Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Pediatric Dentistry, Faculty of Dentistry, Shahed University, Tehran, Iran.
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16
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Nassiri SM, Ahmadi Afshar N, Almasi P. Insight into microRNAs' involvement in hematopoiesis: current standing point of findings. Stem Cell Res Ther 2023; 14:282. [PMID: 37794439 PMCID: PMC10552299 DOI: 10.1186/s13287-023-03504-3] [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: 12/28/2022] [Accepted: 09/20/2023] [Indexed: 10/06/2023] Open
Abstract
Hematopoiesis is a complex process in which hematopoietic stem cells are differentiated into all mature blood cells (red blood cells, white blood cells, and platelets). Different microRNAs (miRNAs) involve in several steps of this process. Indeed, miRNAs are small single-stranded non-coding RNA molecules, which control gene expression by translational inhibition and mRNA destabilization. Previous studies have revealed that increased or decreased expression of some of these miRNAs by targeting several proto-oncogenes could inhibit or stimulate the myeloid and erythroid lineage commitment, proliferation, and differentiation. During the last decades, the development of molecular and bioinformatics techniques has led to a comprehensive understanding of the role of various miRNAs in hematopoiesis. The critical roles of miRNAs in cell processes such as the cell cycle, apoptosis, and differentiation have been confirmed as well. However, the main contribution of some miRNAs is still unclear. Therefore, it seems undeniable that future studies are required to focus on miRNA activities during various hematopoietic stages and hematological malignancy.
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Affiliation(s)
- Seyed Mahdi Nassiri
- Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Qarib St., Azadi Ave, Tehran, Iran.
| | - Neda Ahmadi Afshar
- Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Qarib St., Azadi Ave, Tehran, Iran
| | - Parsa Almasi
- Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Qarib St., Azadi Ave, Tehran, Iran
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17
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Konteles V, Papathanasiou I, Tzetis M, Goussetis E, Trachana V, Mourmoura E, Balis C, Malizos K, Tsezou A. Integration of Transcriptome and MicroRNA Profile Analysis of iMSCs Defines Their Rejuvenated State and Conveys Them into a Novel Resource for Cell Therapy in Osteoarthritis. Cells 2023; 12:1756. [PMID: 37443790 PMCID: PMC10340510 DOI: 10.3390/cells12131756] [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: 03/24/2023] [Revised: 06/18/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Although MSCs grant pronounced potential for cell therapies, several factors, such as their heterogeneity restrict their use. To overcome these limitations, iMSCs (MSCs derived from induced pluripotent stem cells (iPSCs) have attracted attention. Here, we analyzed the transcriptome of MSCs, iPSCs and iMSCs derived from healthy individuals and osteoarthritis (OA) patients and explored miRNA-mRNA interactions during these transitions. We performed RNA-seq and gene expression comparisons and Protein-Protein-Interaction analysis followed by GO enrichment and KEGG pathway analyses. MicroRNAs' (miRNA) expression profile using miRarrays and differentially expressed miRNA's impact on regulating iMSCs gene expression was also explored. Our analyses revealed that iMSCs derivation from iPSCs favors the expression of genes conferring high proliferation, differentiation, and migration properties, all of which contribute to a rejuvenated state of iMSCs compared to primary MSCs. Additionally, our exploration of the involvement of miRNAs in this rejuvenated iMSCs transcriptome concluded in twenty-six miRNAs that, as our analysis showed, are implicated in pluripotency. Notably, the identified here interactions between hsa-let7b/i, hsa-miR-221/222-3p, hsa-miR-302c, hsa-miR-181a, hsa-miR-331 with target genes HMGA2, IGF2BP3, STARD4, and APOL6 could prove to be the necessary tools that will convey iMSCs into the ideal mean for cell therapy in osteoarthritis.
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Affiliation(s)
- Vasileios Konteles
- Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (V.K.); (I.P.)
| | - Ioanna Papathanasiou
- Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (V.K.); (I.P.)
- Department of Biology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece;
| | - Maria Tzetis
- Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Evgenios Goussetis
- Stem Cell Transplant Unit, Aghia Sophia Children’s Hospital, 11527 Athens, Greece;
| | - Varvara Trachana
- Department of Biology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece;
| | - Evanthia Mourmoura
- Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (V.K.); (I.P.)
| | - Charalampos Balis
- Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (V.K.); (I.P.)
| | - Konstantinos Malizos
- Department of Orthopaedics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece
| | - Aspasia Tsezou
- Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (V.K.); (I.P.)
- Department of Biology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece;
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18
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Drobiova H, Sindhu S, Ahmad R, Haddad D, Al-Mulla F, Al Madhoun A. Wharton's jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications. Front Cell Dev Biol 2023; 11:1211217. [PMID: 37440921 PMCID: PMC10333601 DOI: 10.3389/fcell.2023.1211217] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/13/2023] [Indexed: 07/15/2023] Open
Abstract
Accumulating evidence indicates that most primary Wharton's jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome. These bioactive molecules and factors can either be released directly into the surrounding microenvironment or can be embedded within the membrane-bound extracellular bioactive nano-sized (usually 30-150 nm) messenger particles or vesicles of endosomal origin with specific route of biogenesis, known as exosomes or carried by relatively larger particles (100 nm-1 μm) formed by outward blebbing of plasma membrane called microvesicles (MVs); exosomes and MVs are collectively known as extracellular vesicles (EVs). The bioactive molecules and factors found in secretome are of various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, and regulatory nucleic acid molecules. As expected, the secretome performs different biological functions, such as immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory and anti-fibrotic effects. This review highlights the current advances in research on the WJ-MSCs' secretome and its prospective clinical applications.
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Affiliation(s)
- Hana Drobiova
- Human Genetics Unit, Department of Pathology, College of Medicine, Kuwait University, Jabriya, Kuwait
| | - Sardar Sindhu
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Rasheed Ahmad
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Dasman, Kuwait
| | - Dania Haddad
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Fahd Al-Mulla
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
| | - Ashraf Al Madhoun
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
- Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait
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19
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Blakely B, Shin S, Jin K. Overview of the therapeutic strategies for ER positive breast cancer. Biochem Pharmacol 2023; 212:115552. [PMID: 37068524 PMCID: PMC10394654 DOI: 10.1016/j.bcp.2023.115552] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/30/2023] [Accepted: 04/10/2023] [Indexed: 04/19/2023]
Abstract
Estrogen Receptor is the driving transcription factor in about 75% of all breast cancers, which is the target of endocrine therapies, but drug resistance is a common clinical problem. ESR1 point mutations at the ligand binding domain are frequently identified in metastatic tumor and ctDNA (Circulating tumor DNA) derived from ER positive breast cancer patients with endocrine therapies. Although endocrine therapy and CDK4/6 inhibitor therapy have demonstrated preclinical and clinical benefits for breast cancer, the development of resistance remains a significant challenge and the detailed mechanisms, and potential therapeutic targets in advanced breast cancer yet to be revealed. Since a crosstalk between tumor and tumor microenvironment (TME) plays an important role to grow tumor and metastasis, this effect could serve as key regulators in the resistance of endocrine therapy and the transition of breast cancer cells to metastasis. In this article, we have reviewed recent progress in endocrine therapy and the contribution of TME to ER positive breast cancer.
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Affiliation(s)
- Brianna Blakely
- Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Science, Albany, NY, United States
| | - Seobum Shin
- Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Science, Albany, NY, United States
| | - Kideok Jin
- Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Science, Albany, NY, United States.
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Hu Q, Huang T. Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition. Int J Mol Sci 2023; 24:ijms24108939. [PMID: 37240281 DOI: 10.3390/ijms24108939] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
Cyclin-dependent kinases (CDKs) regulate cell division at multiple levels. Aberrant proliferation induced by abnormal cell cycle is a hallmark of cancer. Over the past few decades, several drugs that inhibit CDK activity have been created to stop the development of cancer cells. The third generation of selective CDK4/6 inhibition has proceeded into clinical trials for a range of cancers and is quickly becoming the backbone of contemporary cancer therapy. Non-coding RNAs, or ncRNAs, do not encode proteins. Many studies have demonstrated the involvement of ncRNAs in the regulation of the cell cycle and their abnormal expression in cancer. By interacting with important cell cycle regulators, preclinical studies have demonstrated that ncRNAs may decrease or increase the treatment outcome of CDK4/6 inhibition. As a result, cell cycle-associated ncRNAs may act as predictors of CDK4/6 inhibition efficacy and perhaps present novel candidates for tumor therapy and diagnosis.
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Affiliation(s)
- Qingyi Hu
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Tao Huang
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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21
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Su D, Swearson S, Krongbaramee T, Sun H, Hong L, Amendt BA. Exploring microRNAs in craniofacial regenerative medicine. Biochem Soc Trans 2023; 51:841-854. [PMID: 37073783 PMCID: PMC11244734 DOI: 10.1042/bst20221448] [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: 11/14/2022] [Revised: 03/27/2023] [Accepted: 03/29/2023] [Indexed: 04/20/2023]
Abstract
microRNAs (miRs) have been reported over the decades as important regulators in bone development and bone regeneration. They play important roles in maintaining the stem cell signature as well as regulating stem cell fate decisions. Thus, delivering miRs and miR inhibitors to the defect site is a potential treatment towards craniofacial bone defects. However, there are challenges in translation of basic research to clinics, including the efficiency, specificity, and efficacy of miR manipulation methods and the safety of miR delivery systems. In this review, we will compare miR oligonucleotides, mimics and antagomirs as therapeutic reagents to treat disease and regenerate tissues. Newer technology will be discussed as well as the efficiency and efficacy of using these technologies to express or inhibit miRs in treating and repairing oral tissues. Delivery of these molecules using extracellular vesicles and nanoparticles can achieve different results and depending on their composition will elicit specific effects. We will highlight the specificity, toxicity, stability, and effectiveness of several miR systems in regenerative medicine.
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Affiliation(s)
- Dan Su
- Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA, U.S.A
- Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA, U.S.A
| | - Samuel Swearson
- Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA, U.S.A
| | - Tadkamol Krongbaramee
- Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, U.S.A
- Division of Endodontics, Department of Restorative Dentistry & Periodontology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Hongli Sun
- Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, U.S.A
| | - Liu Hong
- Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA, U.S.A
- Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, U.S.A
| | - Brad A Amendt
- Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA, U.S.A
- Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA, U.S.A
- Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, U.S.A
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22
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Cai X, Wang H, Han Y, Huang H, Qian P. The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis. Front Mol Biosci 2023; 10:1176416. [PMID: 37065445 PMCID: PMC10102602 DOI: 10.3389/fmolb.2023.1176416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 03/23/2023] [Indexed: 04/03/2023] Open
Abstract
Hematopoietic stem cells (HSCs) developing from mesoderm during embryogenesis are important for the blood circulatory system and immune system. Many factors such as genetic factors, chemical exposure, physical radiation, and viral infection, can lead to the dysfunction of HSCs. Hematological malignancies (involving leukemia, lymphoma, and myeloma) were diagnosed in more than 1.3 million people globally in 2021, taking up 7% of total newly-diagnosed cancer patients. Although many treatments like chemotherapy, bone marrow transplantation, and stem cell transplantation have been applied in clinical therapeutics, the average 5-year survival rate for leukemia, lymphoma, and myeloma is about 65%, 72%, and 54% respectively. Small non-coding RNAs play key roles in a variety of biological processes, including cell division and proliferation, immunological response and cell death. With the development of technologies in high-throughput sequencing and bioinformatic analysis, there is emerging research about modifications on small non-coding RNAs, as well as their functions in hematopoiesis and related diseases. In this study, we summarize the updated information of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis, which sheds lights into the future application of HSCs into the treatment of blood diseases.
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Affiliation(s)
- Xinyi Cai
- Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China
| | - Hui Wang
- Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China
| | - Yingli Han
- Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China
| | - He Huang
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China
- Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Pengxu Qian
- Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
- Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China
- *Correspondence: Pengxu Qian,
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23
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Peeples ES. MicroRNA therapeutic targets in neonatal hypoxic-ischemic brain injury: a narrative review. Pediatr Res 2023; 93:780-788. [PMID: 35854090 DOI: 10.1038/s41390-022-02196-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/25/2022] [Accepted: 06/28/2022] [Indexed: 11/11/2022]
Abstract
Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. Despite the use of therapeutic hypothermia, more than one in four survivors suffer from major developmental disabilities-an indication of the critical need for more effective therapies. MicroRNAs (miRNA) have the potential to act as biomarkers and/or therapeutic targets in neonatal HIBI as a step toward improving outcomes in this high-risk population. This review summarizes the current literature around the use of cord blood and postnatal circulating blood miRNA expression for diagnosis or prognosis in human infants with hypoxic-ischemic encephalopathy, as well as animal studies assessing endogenous brain miRNA expression and potential for therapeutic targeting of miRNA expression for neuroprotection. Ultimately, the lack of knowledge regarding brain specificity of circulating miRNAs and the temporal variability in expression currently limit the use of miRNAs as biomarkers. However, given their broad effect profile, ease of administration, and small size allowing for effective blood-brain barrier crossing, miRNAs represent promising therapeutic targets for improving brain injury and reducing developmental impairments in neonates after HIBI. IMPACT: The high morbidity and mortality of neonatal hypoxic-ischemic brain injury (HIBI) despite current therapies demonstrates a need for developing more sensitive biomarkers and superior therapeutic options. MicroRNAs have been evaluated both as biomarkers and therapeutic options after neonatal HIBI. The limited knowledge regarding brain specificity of circulating microRNAs and temporal variability in expression currently limit the use of microRNAs as biomarkers. Future studies comparing the neuroprotective effects of modulating microRNA expression must consider temporal changes in the endogenous expression to determine appropriate timing of therapy, while also optimizing techniques for delivery.
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Affiliation(s)
- Eric S Peeples
- Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
- Children's Hospital & Medical Center, Omaha, NE, USA.
- Child Health Research Institute, Omaha, NE, USA.
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24
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Mohamed Rasheed ZB, Nordin F, Wan Kamarul Zaman WS, Tan YF, Abd Aziz NH. Autologous Human Mesenchymal Stem Cell-Based Therapy in Infertility: New Strategies and Future Perspectives. BIOLOGY 2023; 12:108. [PMID: 36671799 PMCID: PMC9855776 DOI: 10.3390/biology12010108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 01/06/2023] [Accepted: 01/08/2023] [Indexed: 01/12/2023]
Abstract
Infertility could be associated with a few factors including problems with physical and mental health, hormonal imbalances, lifestyles, and genetic factors. Given that there is a concern about the rise of infertility globally, increased focus has been given to its treatment for the last several decades. Traditional assisted reproductive technology (ART) has been the prime option for many years in solving various cases of infertility; however, it contains significant risks and does not solve the fundamental problem of infertility such as genetic disorders. Attention toward the utilization of MSCs has been widely regarded as a promising option in the development of stem-cell-based infertility treatments. This narrative review briefly presents the challenges in the current ART treatment of infertility and the various potential applications of autologous MSCs in the treatment of these reproductive diseases.
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Affiliation(s)
- Zahirrah Begam Mohamed Rasheed
- UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Fazlina Nordin
- Centre for Tissue Engineering and Regenerative Medicine (CTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | | | - Yuen-Fen Tan
- PPUKM-MAKNA Cancer Center, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, WPKL, Kuala Lumpur 56000, Malaysia
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long Campus, Bandar Sungai Long, Kajang 43000, Malaysia
| | - Nor Haslinda Abd Aziz
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- Research Laboratory of UKM Specialist Children’s Hospital, UKM Specialist Children’s Hospital, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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25
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Baghel VS, Shinde S, Sinha V, Dixit V, Tiwari AK, Saxena S, Vishvakarma NK, Shukla D, Bhatt P. Inhibitors targeting epigenetic modifications in cancer. TRANSCRIPTION AND TRANSLATION IN HEALTH AND DISEASE 2023:287-324. [DOI: 10.1016/b978-0-323-99521-4.00007-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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26
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Wang Z, Xie W, Guan H. The diagnostic, prognostic role and molecular mechanism of miR-328 in human cancer. Biomed Pharmacother 2023; 157:114031. [PMID: 36413837 DOI: 10.1016/j.biopha.2022.114031] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/06/2022] [Accepted: 11/17/2022] [Indexed: 11/20/2022] Open
Abstract
MicroRNA are non-coding small RNAs that bind to their target mRNA and cause mRNA degradation or translation inhibition. MiRNA dysregulation is linked to a variety of human cancers and has a role in the genesis and development of cancer pathology. MiR-328 has been reported to be involved in various human cancers. And miR-328 is considered a key regulator in human cancer. It participates in biological processes such as proliferation, apoptosis, invasion, migration, and EMT. The present review will combine the basic and clinical studies to find that miR-328 promotes tumorigenesis and metastasis in human cancer. And we will describe the diagnostic, prognostic, and therapeutic value of miR-328 in various human cancers.
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Affiliation(s)
- Zhichao Wang
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
| | - Wenjie Xie
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
| | - Hongzai Guan
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China.
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27
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Koo B, Kim Y, Jang YO, Liu H, Kim MG, Lee HJ, Woo MK, Kim C, Shin Y. A novel platform using homobifunctional hydrazide for enrichment and isolation of urinary circulating RNAs. Bioeng Transl Med 2023; 8:e10348. [PMID: 36684108 PMCID: PMC9842063 DOI: 10.1002/btm2.10348] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/22/2022] [Accepted: 05/06/2022] [Indexed: 01/25/2023] Open
Abstract
Changes in specific circulating RNA (circRNA) expressions can serve as diagnostic noninvasive biomarkers for prostate cancer (PCa). However, there are still unmet needs, such as unclear types and roles of circRNAs, PCa detection in benign prostatic hyperplasia (BPH) by unstandardized methods, and limitations of sample volume capacity and low circRNA concentrations. This study reports a simple and rapid circRNA enrichment and isolation technique named "HAZIS-CirR" for the analysis of urinary circRNAs. The method utilizes homobifunctional hydrazides with amine-modified zeolite and polyvinylidene fluoride (PVDF) syringe filtration for combining electrostatic and covalent coupling and size-based filtration, and it offers instrument-free isolation of circRNAs in 20 min without volume limitation, thermoregulation, and lysis. HAZIS-CirR has high capture efficiency (82.03%-92.38%) and a 10-fold more sensitive detection limit (20 fM) than before enrichment (200 fM). The clinical utility of HAZIS-CirR is confirmed by analyzing circulating mRNAs and circulating miRNAs in 89 urine samples. Furthermore, three miRNA panels that differentiate PCa from BPH and control, PCa from control, and BPH from control, respectively, are established by comparing miRNA levels. HAZIS-CirR will be used as an optimal and established method for the enrichment and isolation of circRNAs as diagnostic, prognostic, and predictive biomarkers in human cancers.
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Affiliation(s)
- Bonhan Koo
- Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeodaemun‐gu, SeoulRepublic of Korea
| | - Yunlim Kim
- Department of Urology, Asan Medical CenterUniversity of Ulsan College of MedicineSongpa‐gu, SeoulRepublic of Korea
| | - Yoon Ok Jang
- Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeodaemun‐gu, SeoulRepublic of Korea
| | - Huifang Liu
- Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeodaemun‐gu, SeoulRepublic of Korea
| | - Myoung Gyu Kim
- Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeodaemun‐gu, SeoulRepublic of Korea
| | - Hyo Joo Lee
- Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeodaemun‐gu, SeoulRepublic of Korea
| | - Myung Kyun Woo
- Department of Biomedical EngineeringSchool of Electrical Engineering, University of UlsanNam‐gu, UlsanRepublic of Korea
| | - Choung‐Soo Kim
- Department of Urology, Asan Medical CenterUniversity of Ulsan College of MedicineSongpa‐gu, SeoulRepublic of Korea
- Department of UrologyEwha Womans University Mokdong HospitalYangcheon‐gu, SeoulRepublic of Korea
| | - Yong Shin
- Department of Biotechnology, College of Life Science and BiotechnologyYonsei UniversitySeodaemun‐gu, SeoulRepublic of Korea
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28
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Han H, Park CK, Choi YD, Cho NH, Lee J, Cho KS. Androgen-Independent Prostate Cancer Is Sensitive to CDC42-PAK7 Kinase Inhibition. Biomedicines 2022; 11:101. [PMID: 36672609 PMCID: PMC9855385 DOI: 10.3390/biomedicines11010101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 12/23/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
Prostate cancer is a common form of cancer in men, and androgen-deprivation therapy (ADT) is often used as a first-line treatment. However, some patients develop resistance to ADT, and their disease is called castration-resistant prostate cancer (CRPC). Identifying potential therapeutic targets for this aggressive subtype of prostate cancer is crucial. In this study, we show that statins can selectively inhibit the growth of these CRPC tumors that have lost their androgen receptor (AR) and have overexpressed the RNA-binding protein QKI. We found that the repression of microRNA-200 by QKI overexpression promotes the rise of AR-low mesenchymal-like CRPC cells. Using in silico drug/gene perturbation combined screening, we discovered that QKI-overexpressing cancer cells are selectively vulnerable to CDC42-PAK7 inhibition by statins. We also confirmed that PAK7 overexpression is present in prostate cancer that coexists with hyperlipidemia. Our results demonstrate a previously unseen mechanism of action for statins in these QKI-expressing AR-lost CRPCs. This may explain the clinical benefits of the drug and support the development of a biology-driven drug-repurposing clinical trial. This is an important finding that could help improve treatment options for patients with this aggressive form of prostate cancer.
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Affiliation(s)
- Hyunho Han
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Cheol Keun Park
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Pathology Center, Seegene Medical Foundation, Seoul 04805, Republic of Korea
| | - Young-Deuk Choi
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Nam Hoon Cho
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jongsoo Lee
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Kang Su Cho
- Department of Urology, Prostate Cancer Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06229, Republic of Korea
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29
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Rajabi A, Kayedi M, Rahimi S, Dashti F, Mirazimi SMA, Homayoonfal M, Mahdian SMA, Hamblin MR, Tamtaji OR, Afrasiabi A, Jafari A, Mirzaei H. Non-coding RNAs and glioma: Focus on cancer stem cells. Mol Ther Oncolytics 2022; 27:100-123. [PMID: 36321132 PMCID: PMC9593299 DOI: 10.1016/j.omto.2022.09.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Glioblastoma and gliomas can have a wide range of histopathologic subtypes. These heterogeneous histologic phenotypes originate from tumor cells with the distinct functions of tumorigenesis and self-renewal, called glioma stem cells (GSCs). GSCs are characterized based on multi-layered epigenetic mechanisms, which control the expression of many genes. This epigenetic regulatory mechanism is often based on functional non-coding RNAs (ncRNAs). ncRNAs have become increasingly important in the pathogenesis of human cancer and work as oncogenes or tumor suppressors to regulate carcinogenesis and progression. These RNAs by being involved in chromatin remodeling and modification, transcriptional regulation, and alternative splicing of pre-mRNA, as well as mRNA stability and protein translation, play a key role in tumor development and progression. Numerous studies have been performed to try to understand the dysregulation pattern of these ncRNAs in tumors and cancer stem cells (CSCs), which show robust differentiation and self-regeneration capacity. This review provides recent findings on the role of ncRNAs in glioma development and progression, particularly their effects on CSCs, thus accelerating the clinical implementation of ncRNAs as promising tumor biomarkers and therapeutic targets.
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Affiliation(s)
- Ali Rajabi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Mehrdad Kayedi
- Department of Radiology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shiva Rahimi
- School of Medicine,Fasa University of Medical Sciences, Fasa, Iran
| | - Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Mohammad Ali Mirazimi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Mina Homayoonfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Mohammad Amin Mahdian
- Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael R. Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
| | - Omid Reza Tamtaji
- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Afrasiabi
- Department of Internal Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ameneh Jafari
- Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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30
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Tang X, Lin Y, He J, Luo X, Liang J, Zhu X. Downregulated miRNA-491-3p accelerates colorectal cancer growth by increasing uMtCK expression. PeerJ 2022; 10:e14285. [PMID: 36518289 PMCID: PMC9744150 DOI: 10.7717/peerj.14285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/02/2022] [Indexed: 11/29/2022] Open
Abstract
Colorectal carcinoma (CRC) is the second most frequent cancer worldwide. MiR-491-3p, a tumor-suppressive microRNA (miRNA, miR), has been revealed to be abnormally expressed in CRC tissues. Meanwhile, up-regulated ubiquitous mitochondrial creatine kinase (uMtCK) contributes to CRC cell proliferation. Here we aim to explore whether aberrant miR-491-3p expression promotes CRC progression through regulating uMtCK. To this end, miR-491-3p and uMtCK levels were assessed in CRC tissues using quantitative real-time PCR (qRT-PCR). The biological roles of miR-491-3p and uMtCK in regulating CRC growth were evaluated using colony formation assay and mouse Xenograft tumour model. We found that miR-491-3p expression was decreased in CRC tissues compared with matched para-cancerous tissues, whereas uMtCK expression was increased. Functionally, miR-491-3p overexpression repressed SW480 cell growth, whereas miR-491-3p depletion accelerated SW620 cell proliferation and growth. Inversely, uMtCK positively regulated CRC cell proliferation. Mechanistically, miR-491-3p post-transcriptionally downregulated uMtCK expression by binding to 3'-UTR of uMtCK. Consequently, restoring uMtCK expression markedly eliminated the role of miR-491-3p in suppressing CRC growth. Collectively, miR-491-3p functions as a tumour suppressor gene by repressing uMtCK, and may be a potential target for CRC treatment.
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Affiliation(s)
- Xingkui Tang
- Department of General Surgery, Panyu District Central Hospital, Guangzhou, China
| | - Yukun Lin
- Department of Electron Microscopy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Jialin He
- Department of General Surgery, Panyu District Central Hospital, Guangzhou, China
| | - Xijun Luo
- Department of General Surgery, Panyu District Central Hospital, Guangzhou, China
| | - Junjie Liang
- Department of General Surgery, Panyu District Central Hospital, Guangzhou, China
| | - Xianjun Zhu
- Department of General Surgery, Panyu District Central Hospital, Guangzhou, China
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31
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Shree N, Ding Z, Flaws J, Choudhury M. Role of microRNA in Endocrine Disruptor-Induced Immunomodulation of Metabolic Health. Metabolites 2022; 12:1034. [PMID: 36355117 PMCID: PMC9695656 DOI: 10.3390/metabo12111034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 10/25/2022] [Accepted: 10/26/2022] [Indexed: 01/22/2025] Open
Abstract
The prevalence of poor metabolic health is growing exponentially worldwide. This condition is associated with complex comorbidities that lead to a compromised quality of life. One of the contributing factors recently gaining attention is exposure to environmental chemicals, such as endocrine-disrupting chemicals (EDCs). Considerable evidence suggests that EDCs can alter the endocrine system through immunomodulation. More concerning, EDC exposure during the fetal development stage has prominent adverse effects later in life, which may pass on to subsequent generations. Although the mechanism of action for this phenomenon is mostly unexplored, recent reports implicate that non-coding RNAs, such as microRNAs (miRs), may play a vital role in this scenario. MiRs are significant contributors in post-transcriptional regulation of gene expression. Studies demonstrating the immunomodulation of EDCs via miRs in metabolic health or towards the Developmental Origins of Health and Disease (DOHaD) Hypothesis are still deficient. The aim of the current review was to focus on studies that demonstrate the impact of EDCs primarily on innate immunity and the potential role of miRs in metabolic health.
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Affiliation(s)
- Nitya Shree
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University (TAMU), College Station, TX 77843, USA
| | - Zehuan Ding
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University (TAMU), College Station, TX 77843, USA
| | - Jodi Flaws
- Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA
| | - Mahua Choudhury
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University (TAMU), College Station, TX 77843, USA
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Yahaya TO, Bashar DM, Oladele EO, Umar J, Anyebe D, Izuafa A. Epigenetics in the etiology and management of infertility. World J Med Genet 2022; 10:7-21. [DOI: 10.5496/wjmg.v10.i2.7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 06/28/2022] [Accepted: 10/12/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Epigenetic disruptions have been implicated in some cases of infertility and can serve as therapeutic targets. However, the involvement of epigenetics in infertility has not received adequate attention.
AIM This study aimed to determine the epigenetic basis of infertility in order to enhance public knowledge.
METHODS Relevant articles on the subject were collected from PubMed, RCA, Google Scholar, SpringerLink, and Scopus. The articles were pooled together and duplicates were removed using Endnote software.
RESULTS Available information shows that epigenetic mechanisms, mainly DNA methylation, histone modification, and microRNA interference are necessary for normal gametogenesis and embryogenesis. As a result, epigenetic disruptions in genes that control gametogenesis and embryogenesis, such as DDX3X, ADH4, AZF, PLAG1, D1RAS3, CYGB, MEST, JMJD1A, KCNQ1, IGF2, H19, and MTHFR may result in infertility. Aberrant DNA methylation during genomic imprinting and parental epigenetic mark erasures, in particular, may affect the DNA epigenomes of sperm and oocytes, resulting in reproductive abnormalities. Histone epigenetic dysregulation during oocyte development and histone-protamine replacement in the sperm may also cause reproductive abnormalities. Furthermore, overexpression or repression of certain microRNAs embedded in the ovary, testis, embryo, as well as granulosa cells and oocytes may impair reproduction. Male infertility is characterized by spermatogenesis failure, which includes oligozoospermia, asthenozoospermia, and teratozoospermia, while female infertility is characterized by polycystic ovary syndrome. Some epigenetic modifications can be reversed by deactivating the regulatory enzymes, implying that epigenetic reprogramming could help treat infertility in some cases. For some disorders, epigenetic drugs are available, but none have been formulated for infertility.
CONCLUSION Some cases of infertility have an epigenetic etiology and can be treated by reversing the same epigenetic mechanism that caused it. As a result, medical practitioners are urged to come up with epigenetic treatments for infertility that have an epigenetic cause.
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Affiliation(s)
| | - Danlami M Bashar
- Department of Microbiology, Federal University Birnin Kebbi, Kebbi State 23401, Nigeria
| | - Esther O Oladele
- Biology Unit, Distance Learning Institute, University of Lagos, Lagos State 23401, Nigeria
| | - Ja'afar Umar
- Department of Biological Sciences, Federal University Birnin Kebbi, Kebbi State 23401, Nigeria
| | - Daniel Anyebe
- Department of Biochemistry and Molecular Biology, Federal University Birnin Kebbi, Kebbi State 23401, Nigeria
| | - Abdulrazaq Izuafa
- Department of Biological Sciences, Federal University Birnin Kebbi, Kebbi State 23401, Nigeria
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Lim R, Banerjee A, Biswas R, Chari AN, Raghavan S. Mechanotransduction through adhesion molecules: Emerging roles in regulating the stem cell niche. Front Cell Dev Biol 2022; 10:966662. [PMID: 36172276 PMCID: PMC9511051 DOI: 10.3389/fcell.2022.966662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 07/18/2022] [Indexed: 11/23/2022] Open
Abstract
Stem cells have been shown to play an important role in regenerative medicine due to their proliferative and differentiation potential. The challenge, however, lies in regulating and controlling their potential for this purpose. Stem cells are regulated by growth factors as well as an array of biochemical and mechanical signals. While the role of biochemical signals and growth factors in regulating stem cell homeostasis is well explored, the role of mechanical signals has only just started to be investigated. Stem cells interact with their niche or to other stem cells via adhesion molecules that eventually transduce mechanical cues to maintain their homeostatic function. Here, we present a comprehensive review on our current understanding of the influence of the forces perceived by cell adhesion molecules on the regulation of stem cells. Additionally, we provide insights on how this deeper understanding of mechanobiology of stem cells has translated toward therapeutics.
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Affiliation(s)
- Ryan Lim
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
| | - Avinanda Banerjee
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
| | - Ritusree Biswas
- Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore, India
- Sastra University, Thanjavur, TN, India
| | - Anana Nandakumar Chari
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
| | - Srikala Raghavan
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
- Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore, India
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Bi Y, Qiao X, Liu Q, Song S, Zhu K, Qiu X, Zhang X, Jia C, Wang H, Yang Z, Zhang Y, Ji G. Systemic proteomics and miRNA profile analysis of exosomes derived from human pluripotent stem cells. Stem Cell Res Ther 2022; 13:449. [PMID: 36064647 PMCID: PMC9444124 DOI: 10.1186/s13287-022-03142-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/16/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Increasing studies have reported the therapeutic effect of mesenchymal stem cell (MSC)-derived exosomes by which protein and miRNA are clearly characterized. However, the proteomics and miRNA profiles of exosomes derived from human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) remain unclear. METHODS In this study, we isolated exosomes from hESCs, hiPSCs, and human umbilical cord mesenchymal stem cells (hUC-MSCs) via classic ultracentrifugation and a 0.22-μm filter, followed by the conservative identification. Tandem mass tag labeling and label-free relative peptide quantification together defined their proteomics. High-throughput sequencing was performed to determine miRNA profiles. Then, we conducted a bioinformatics analysis to identify the dominant biological processes and pathways modulated by exosome cargos. Finally, the western blot and RT-qPCR were performed to detect the actual loads of proteins and miRNAs in three types of exosomes. RESULTS Based on our study, the cargos from three types of exosomes contribute to sophisticated biological processes. In comparison, hESC exosomes (hESC-Exos) were superior in regulating development, metabolism, and anti-aging, and hiPSC exosomes (hiPSC-Exos) had similar biological functions as hESC-Exos, whereas hUC-MSCs exosomes (hUC-MSC-Exos) contributed more to immune regulation. CONCLUSIONS The data presented in our study help define the protein and miRNA landscapes of three exosomes, predict their biological functions via systematic and comprehensive network analysis at the system level, and reveal their respective potential applications in different fields so as to optimize exosome selection in preclinical and clinical trials.
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Affiliation(s)
- Youkun Bi
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xinlong Qiao
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Qun Liu
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Shaole Song
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Keqi Zhu
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xun Qiu
- Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China
| | - Xiang Zhang
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Ce Jia
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Huiwen Wang
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Zhiguang Yang
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Ying Zhang
- Sixth Department of Liver Disease, Dalian Public Health Clinical Center, Dalian Medical University, Dalian, 116023, China.
| | - Guangju Ji
- Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
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Qing Y, Yang Y, Ouyang P, Fang C, Fang H, Liao Y, Li H, Wang Z, Du J. Gold Nanoparticle-Based Enzyme-Assisted Cyclic Amplification for the Highly-Sensitive Detection of miRNA-21. BIOSENSORS 2022; 12:bios12090724. [PMID: 36140109 PMCID: PMC9496089 DOI: 10.3390/bios12090724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 08/28/2022] [Accepted: 09/01/2022] [Indexed: 12/27/2022]
Abstract
Because microRNAs (miRNAs) are biological indicators for the diagnosis, treatment, and monitoring of tumors, cancers, and other diseases, it is significant to develop a rapid, sensitive, and reliable miRNA detection platform. In this study, based on miRNA-21 detection, DNA-a with a 3′ end overhang and Texas Red fluorophore-labeled 5′ end was designed, which reacts with miRNA-21 and hybridizes with exonuclease III (Exo III), where the part connected to miRNA-21 is hydrolyzed, leaving a-DNA. At the same time, miRNA-21 is released to participate in the following reaction, to achieve cyclic amplification. a-DNA reacts with DNA-b conjugated to gold nanoparticles to achieve fluorescence quenching, with the quenching value denoted as F; additionally, after adding DNA-d and linked streptavidin immunomagnetic beads (SIBs), fluorescence recovery was achieved using DNA-c, with the recovered fluorescence recorded as F0. By comparing the difference in the fluorescence (F0 − F) between the two experiments, the amount of DNA-a hydrolyzed to produce a-DNA was established to determine the target miRNA-21 content. Under optimized conditions, by comparing the changes in the fluorescence signal, the developed strategy shows good sensitivity and repeatability, with a detection limit of 18 pM, good discriminative ability and selectivity, and promise for the early diagnosis of breast and intestinal cancers.
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Wang L, Zhen H, Sun Y, Rong S, Li B, Song Z, Liu Z, Li Z, Ding J, Yang H, Zhang X, Sun H, Nie C. Plasma Exo-miRNAs Correlated with AD-Related Factors of Chinese Individuals Involved in Aβ Accumulation and Cognition Decline. Mol Neurobiol 2022; 59:6790-6804. [PMID: 36040555 PMCID: PMC9425792 DOI: 10.1007/s12035-022-03012-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 07/29/2022] [Indexed: 11/17/2022]
Abstract
Numerous studies have investigated the risk factors of Alzheimer’s disease (AD); however, AD-risk factors related miRNAs were rarely reported. In this study, AD-risk factor related miRNAs of 105 Chinese individuals (45 AD patients and 60 cognitively normal controls) were investigated. The results showed that Hsa-miR-185-5p, Hsa-miR-20a-5p, and Hsa-miR-497-5p were related to AD and education, Hsa-miR-185-5p, Hsa-miR-181c-5p, Hsa-miR-664a-3p, Hsa-miR-27a-3p, Hsa-miR-451a, and Hsa-miR-320a were related to AD and depression. Target prediction of above miRNAs showed that these miRNAs were involved in the generation and clearance of amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. It is worth noting that Hsa-miR-185-5p was related to both education and depression, whose decreased expression pattern in AD patients was alleviated by education and enhanced by depression, and participates in Aβ generation and accumulation. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.
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Affiliation(s)
- Lifang Wang
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Hefu Zhen
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Yuzhe Sun
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Shuang Rong
- Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China
| | - Benchao Li
- Department of Nutrition and Food Hygiene, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, China
| | - Zhijie Song
- BGI-Shenzhen, Shenzhen, 518083, China.,James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China
| | - Zhili Liu
- BGI-Shenzhen, Shenzhen, 518083, China.,James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China
| | - Zhiming Li
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Jiahong Ding
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Huanming Yang
- BGI-Shenzhen, Shenzhen, 518083, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xiuqing Zhang
- BGI-Shenzhen, Shenzhen, 518083, China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Haixi Sun
- BGI-Shenzhen, Shenzhen, 518083, China. .,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China. .,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China. .,James D. Watson Institute of Genome Sciences, Hangzhou, 310058, China. .,BGI-Beijing, Beijing, 102601, China.
| | - Chao Nie
- BGI-Shenzhen, Shenzhen, 518083, China. .,China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China. .,Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, 518083, China.
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Ouyang P, Qing Y, Zou S, Fang C, Han J, Yang Y, Li H, Wang Z, Du J. Sensitive detection of miR-122 via toehold-promoted strand displacement reaction and enzyme-assisted cycle amplification. Biochem Eng J 2022. [DOI: 10.1016/j.bej.2022.108576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Chen H, Zhang M, Zhang J, Chen Y, Zuo Y, Xie Z, Zhou G, Chen S, Chen Y. Application of Induced Pluripotent Stem Cell-Derived Models for Investigating microRNA Regulation in Developmental Processes. Front Genet 2022; 13:899831. [PMID: 35719367 PMCID: PMC9204592 DOI: 10.3389/fgene.2022.899831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 05/06/2022] [Indexed: 11/29/2022] Open
Abstract
Advances in induced pluripotent stem cell (iPSC) techniques have opened up new perspectives in research on developmental biology. Compared with other sources of human cellular models, iPSCs present a great advantage in hosting the unique genotype background of donors without ethical concerns. A wide spectrum of cellular and organoid models can be generated from iPSCs under appropriate in vitro conditions. The pluripotency of iPSCs is orchestrated by external signalling and regulated at the epigenetic, transcriptional and posttranscriptional levels. Recent decades have witnessed the progress of studying tissue-specific expressions and functions of microRNAs (miRNAs) using iPSC-derived models. MiRNAs are a class of short non-coding RNAs with regulatory functions in various biological processes during development, including cell migration, proliferation and apoptosis. MiRNAs are key modulators of gene expression and promising candidates for biomarker in development; hence, research on the regulation of human development by miRNAs is expanding. In this review, we summarize the current progress in the application of iPSC-derived models to studies of the regulatory roles of miRNAs in developmental processes.
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Affiliation(s)
- Hongyu Chen
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Mimi Zhang
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jingzhi Zhang
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yapei Chen
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yabo Zuo
- Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China
| | - Zhishen Xie
- Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China
| | - Guanqing Zhou
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shehong Chen
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yaoyong Chen
- Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Wang J, Sun N, Ju Y, Ni N, Tang Z, Zhang D, Dai X, Chen M, Wang Y, Gu P, Ji J. miR-381-3p Cooperated With Hes1 to Regulate the Proliferation and Differentiation of Retinal Progenitor Cells. Front Cell Dev Biol 2022; 10:853215. [PMID: 35281083 PMCID: PMC8914042 DOI: 10.3389/fcell.2022.853215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/11/2022] [Indexed: 01/01/2023] Open
Abstract
Retinal progenitor cells (RPCs) transplantation has become a promising therapy for retinal degeneration, which is a major kind of ocular diseases causing blindness. Since RPCs have limited proliferation and differentiation abilities toward retinal neurons, it is urgent to resolve these problems. MicroRNAs have been reported to have vital effects on stem cell fate. In our study, the data showed that overexpression of miR-381-3p repressed Hes1 expression, which promoted RPCs differentiation, especially toward neuronal cells, and inhibited RPCs proliferation. Knockdown of endogenous miR-381-3p increased Hes1 expression to inhibit RPCs differentiation and promote proliferation. In addition, a luciferase assay demonstrated that miR-381-3p directly targeted the Hes1 3’ untranslated region (UTR). Taken together, our study demonstrated that miR-381-3p regulated RPCs proliferation and differentiation by targeting Hes1, which provides an experimental basis of RPCs transplantation therapy for retinal degeneration.
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Affiliation(s)
- Jiajing Wang
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Na Sun
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
- Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yahan Ju
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Ni Ni
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Zhimin Tang
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Dandan Zhang
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Xiaochan Dai
- Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Moxin Chen
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yiqi Wang
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Ping Gu
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
- *Correspondence: Jing Ji, ; Ping Gu,
| | - Jing Ji
- Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
- *Correspondence: Jing Ji, ; Ping Gu,
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Li X, Ren Y, Liu D, Yu X, Chen K. Role of miR-100-5p and CDC25A in breast carcinoma cells. PeerJ 2022; 9:e12263. [PMID: 35036112 PMCID: PMC8734459 DOI: 10.7717/peerj.12263] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 09/16/2021] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE To inquiry about mechanism of miR-100-5p/CDC25A axis in breast carcinoma (BC), thus offering a new direction for BC targeted treatment. METHODS qRT-PCR was employed to explore miR-100-5p and CDC25A mRNA levels. Western blot was employed for detecting protein expression of CDC25A. Targeting relationship of miR-100-5p and CDC25A was verified by dual-luciferase assay. In vitro experiments were used for assessment of cell functions. RESULTS In BC tissue and cells, miR-100-5p was significantly lowly expressed (P < 0.05) while CDC25A was highly expressed. Besides, miR-100-5p downregulated CDC25A level. miR-100-5p had a marked influence on the prognosis of patients. The forced miR-100-5p expression hindered BC cell proliferation, migration and invasion, and facilitated cell apoptosis. Upregulated miR-100-5p weakened promotion of CDC25A on BC cell growth. CONCLUSION Together, these findings unveiled that CDC25A may be a key target of miR-100-5p that mediated progression of BC cells. Hence, miR-100-5p overexpression or CDC25A suppression may contribute to BC diagnosis.
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Affiliation(s)
- Xiaoping Li
- Faculty of Medicine, Macau University of Science and Technology, Macau, China.,Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang province, China
| | - Yanli Ren
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang province, China
| | - Donghong Liu
- Department of Laboratory Medicine, Hangyan hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Zhejiang, China
| | - Xi Yu
- Faculty of Medicine, Macau University of Science and Technology, Macau, China
| | - Keda Chen
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang province, China
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Sobrero M, Montecucco F, Carbone F. Circulating MicroRNAs for Diagnosis of Acute Pulmonary Embolism: Still a Long Way to Go. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4180215. [PMID: 35047634 PMCID: PMC8763471 DOI: 10.1155/2022/4180215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 12/14/2021] [Accepted: 12/30/2021] [Indexed: 12/15/2022]
Abstract
Venous thromboembolism (VTE) represents the third most frequent cause of acute cardiovascular syndrome. Among VTE, acute pulmonary embolism (APE) is the most life-threatening complication. Due to the low specificity of symptoms clinical diagnosis of APE may be sometimes very difficult. Accordingly, the latest European guidelines only suggest clinical prediction tests for diagnosis of APE, eventually associated with D-dimer, a biomarker burdened by a very low specificity. A growing body of evidence is highlighting the role of miRNAs in hemostasis and thrombosis. Due to their partial inheritance and susceptibility to the environmental factors, miRNAs are increasingly described as active modifiers of the classical Virchow's triad. Clinical evidence on deep venous thrombosis reported specific miRNA signatures associated to thrombosis development, organization, recanalization, and resolution. Conversely, data of miRNA profiling as a predictor/diagnostic marker of APE are still preliminary. Here, we have summarized clinical evidence on the potential role of miRNA in diagnosis of APE. Despite some intriguing insight, miRNA assay is still far from any potential clinical application. Especially, the small sample size of cohorts likely represents the major limitation of published studies, so that extensive analysis of miRNA profiles with a machine learning approach are warranted in the next future. In addition, the cost-benefit ratio of miRNA assay still has a negative impact on their clinical application and routinely test.
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Affiliation(s)
- Matteo Sobrero
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
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Okeke C, Silas U, Nnodu O, Clementina O. HSC and miRNA Regulation with Implication for Foetal Haemoglobin Induction in Beta Haemoglobinopathies. Curr Stem Cell Res Ther 2022; 17:339-347. [PMID: 35189805 DOI: 10.2174/1574888x17666220221104711] [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: 09/02/2021] [Revised: 11/29/2021] [Accepted: 12/08/2021] [Indexed: 11/22/2022]
Abstract
Sickle cell disease (SCD) is one of the most common haemoglobinopathies worldwide, with up to 70 % of global SCD annual births occurring in sub-Saharan Africa. Reports have shown that 50 to 80 % of affected children in these countries die annually. Efforts geared towards understanding and controlling HbF production in SCD patients could lead to strategies for effective control of globin gene expression and therapeutic approaches that could be beneficial to individuals with haemoglobinopathies. Hemopoietic stem cells (HSCs) are characterized by a specific miRNA signature in every state of differentiation. The role of miRNAs has become evident both in the maintenance of the "stemness" and in the early induction of differentiation by modulation of the expression of the master pluripotency genes and during early organogenesis. miRNAs are extra regulatory mechanisms in hematopoietic stem cells (HSCs) via influencing transcription profiles together with transcript stability. miRNAs have been reported to be used to reprogram primary somatic cells toward pluripotency. Their involvement in cell editing holds the potential for therapy for many genetic diseases. This review provides a snapshot of miRNA involvement in cell fate decisions, haemoglobin induction pathway, and their journey as some emerge prime targets for therapy in beta haemoglobinopathies.
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Affiliation(s)
- Chinwe Okeke
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, University of Nigeria, Nsukka, Nigeria
| | - Ufele Silas
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, University of Nigeria, Nsukka, Nigeria
| | - Obiageli Nnodu
- Department of Haematology, College of Medicine, University of Abuja, Abuja Nigeria
| | - Odoh Clementina
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, University of Nigeria, Nsukka, Nigeria
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Chen W, Jiang W, Dong J, Wang J, Wang B. MiR-200b-3p induces the formation of insulin-producing cells from umbilical cord mesenchymal stem cells by targeting ZEB2. Crit Rev Eukaryot Gene Expr 2022; 32:33-46. [DOI: 10.1615/critreveukaryotgeneexpr.2022041822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Jiang J, Xin J, Ding W, Shi D, Sun S, Guo B, Zhou X, Zheng C, Li J. MicroRNA Profile of Human Bone Marrow Mesenchymal Stem Cells during Hepatic Differentiation and Therapy. Int J Med Sci 2022; 19:152-163. [PMID: 34975309 PMCID: PMC8692113 DOI: 10.7150/ijms.67639] [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: 10/01/2021] [Accepted: 11/26/2021] [Indexed: 12/05/2022] Open
Abstract
Background and Aims: MicroRNAs (miRNAs) play important roles in hepatocyte differentiation from human bone marrow mesenchymal stem cells (hBMSCs) and the therapeutic application in vivo. However, the mechanisms of miRNA regulation are still unknown. This study aimed to profile the miRNA basis for improving the function of hBMSC-differentiated hepatocyte-like cells (hBMSC-Heps). Methods: Characteristic miRNAs of hBMSC-Heps were identified by transcriptome sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). An in vivo hBMSC transplantation model was used to assess the regulatory effects of miRNAs on liver regeneration during hBMSC therapy in pigs with fulminant hepatic failure (FHF). The biological functions of significant miRNA molecules were confirmed by transfection of miRNA activators or inhibitors into hBMSCs during hepatogenic differentiation. Results: The transcriptome of hBMSC-Heps showed characteristics distinct from those of undifferentiated hBMSCs. A total of 77 miRNAs were significantly differentially expressed in hBMSC-Heps at day 10 and day 20 after hBMSC differentiation that were directly related to the functions of hepatocytes. Among the top 10 significantly differentially expressed and the top 10 most abundant miRNAs, nine miRNAs that exhibited a pattern of gradual change were chosen for further analysis. The expression of nine miRNAs was confirmed by qRT-PCR in vitro and showed the same changing trends in vivo in an hBMSC transplantation model in pigs. Functional experiments with these miRNAs showed that activators of hsa-miR-26b-5p and hsa-miR-148a-3p and an inhibitor of hsa-miR-423-3p were sufficient to improve the differentiation of hBMSCs into hepatocyte-like cells. Conclusions: Transcriptome profiles of miRNA revealed the basis of the differentiation and development of hBMSC-Heps. Manipulation of three miRNAs (hsa-miR-26b-5p, hsa-miR-148a-3p and hsa-miR-423-3p) significantly improved hepatocyte generation and liver regeneration, indicating the potential of these miRNAs for future clinical applications.
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Affiliation(s)
- Jing Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Jiaojiao Xin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Wenchao Ding
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Dongyan Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Suwan Sun
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Beibei Guo
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Xingping Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Chufan Zheng
- Hangzhou No.14 High School, 580 Fengqi Rd, Gongshu District, Hangzhou, 310006, China
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
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Lai X, Schmitz U, Vera J. The Role of MicroRNAs in Cancer Biology and Therapy from a Systems Biology Perspective. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1385:1-22. [DOI: 10.1007/978-3-031-08356-3_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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46
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Jauhari A, Singh T, Yadav S. Neurodevelopmental Disorders and Neurotoxicity: MicroRNA in Focus. J Chem Neuroanat 2022; 120:102072. [DOI: 10.1016/j.jchemneu.2022.102072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 01/16/2022] [Accepted: 01/17/2022] [Indexed: 10/19/2022]
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Chen L, Hamarash II, Jafari S, Rajagopal K, Hussain I. Various bifurcations in the development of stem cells. THE EUROPEAN PHYSICAL JOURNAL. SPECIAL TOPICS 2021; 231:1015-1021. [PMID: 34804377 PMCID: PMC8590129 DOI: 10.1140/epjs/s11734-021-00322-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 10/30/2021] [Indexed: 06/13/2023]
Abstract
Cell development from an undifferentiated stem cell to a differentiated one is essential in forming an organism. In this paper, various bifurcations of a stem cell during this process are studied using a model based on Furusawa and Kaneko's hypothesis. Furusawa and Kaneko's hypothesis tells that the gene expression of stem cells is chaotic. By developing to a differentiated cell, the gene expression in more order, which is the cause of losing pluripotency. In this model, the chaotic dynamics of gene expression in the stem cells become ordered during the developments. Various patterns and bifurcation points can be seen during development. The bifurcation points and their predictions during the process of cell development are studied in this paper. Some well-known critical slowing down indicators are used to show the variations of slowness during the cell's development and predict the bifurcation points. It is vital since the unexpected changes of the state can cause a disaster. All of the indicators have a proper trend by approaching the bifurcation points and faring away.
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Affiliation(s)
- Lianyu Chen
- School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001 China
| | - Ibrahim Ismael Hamarash
- Electrical Engineering Department, Salahaddin University-Erbil, Kirkuk Rd., Erbil, Kurdistan Iraq
- School of Computer Science and Engineering, University of Kurdistan Hewler, 40m St., Erbil, Kurdistan Iraq
| | - Sajad Jafari
- Biomedical Engineering Department, Amirkabir University of Technology, Tehran, 15875-4413 Iran
- Health Technology Research Institute, Amirkabir University of Technology, No.350, Hafez Ave, Valiasr Square, Tehran, 159163-4311 Iran
| | | | - Iqtadar Hussain
- Department of Mathematics, Statistics and Physics, Qatar University, Doha, 2713 Qatar
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Li J, Lu L, Liu Y, Yu X. Bone marrow adiposity during pathologic bone loss: molecular mechanisms underlying the cellular events. J Mol Med (Berl) 2021; 100:167-183. [PMID: 34751809 DOI: 10.1007/s00109-021-02164-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 10/09/2021] [Accepted: 11/03/2021] [Indexed: 02/05/2023]
Abstract
Bone marrow (BM) is a heterogeneous niche where bone marrow stromal cells (BMSCs), osteoblasts, osteoclasts, adipocytes, hematopoietic cells, and immune cells coexist. The cellular composition of BM changes with various pathophysiological states. A reduction in osteoblast number and a concomitant increase in adipocyte number in aging and pathological conditions put bone marrow adipose tissue (BMAT) into spotlight. Accumulating evidence strongly supports that an overwhelming production of BMAT is a major contributor to bone loss disorders. Therefore, BMAT-targeted therapy can be an efficient and feasible intervention for osteoporosis. However, compared to blocking bone-destroying molecules produced by BMAT, suppressing BMAT formation is theoretically a more effective and fundamental approach in treating osteoporotic bone diseases. Thus, a deep insight into the molecular basis underlying increased BM adiposity during pathologic bone loss is critical to formulate strategies for therapeutically manipulating BMAT. In this review, we comprehensively summarize the molecular mechanisms involved in adipocyte differentiation of BMSCs as well as the interaction between bone marrow adipocytes and osteoclasts. More importantly, we further discuss the potential clinical implications of therapeutically targeting the upstream of BMAT formation in bone loss diseases.
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Affiliation(s)
- Jiao Li
- Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan Province, China
| | - Lingyun Lu
- Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan Province, China
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yi Liu
- Department of Rheumatology and Immunology, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xijie Yu
- Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan Province, China
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Nath A, Rayabaram J, Ijee S, Bagchi A, Chaudhury AD, Roy D, Chambayil K, Singh J, Nakamura Y, Velayudhan SR. Comprehensive Analysis of microRNAs in Human Adult Erythropoiesis. Cells 2021; 10:3018. [PMID: 34831239 PMCID: PMC8616439 DOI: 10.3390/cells10113018] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/13/2021] [Accepted: 10/19/2021] [Indexed: 01/08/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs, which play an important role in various cellular and developmental processes. The study of miRNAs in erythropoiesis is crucial to uncover the cellular pathways that are modulated during the different stages of erythroid differentiation. Using erythroid cells derived from human CD34+ hematopoietic stem and progenitor cells (HSPCs)and small RNA sequencing, our study unravels the various miRNAs involved in critical cellular pathways in erythroid maturation. We analyzed the occupancy of erythroid transcription factors and chromatin accessibility in the promoter and enhancer regions of the differentially expressed miRNAs to integrate miRNAs in the transcriptional circuitry of erythropoiesis. Analysis of the targets of the differentially expressed miRNAs revealed novel pathways in erythroid differentiation. Finally, we described the application of Clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) based editing of miRNAs to study their function in human erythropoiesis.
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Affiliation(s)
- Aneesha Nath
- Center for Stem Cell Research (A Unit of InStem, Bengaluru, India), Christian Medical College, Vellore 632002, India; (A.N.); (S.I.); (A.B.); (K.C.)
| | - Janakiram Rayabaram
- Department of Haematology, Christian Medical College, Vellore 632004, India; (J.R.); (A.D.C.); (D.R.)
| | - Smitha Ijee
- Center for Stem Cell Research (A Unit of InStem, Bengaluru, India), Christian Medical College, Vellore 632002, India; (A.N.); (S.I.); (A.B.); (K.C.)
| | - Abhirup Bagchi
- Center for Stem Cell Research (A Unit of InStem, Bengaluru, India), Christian Medical College, Vellore 632002, India; (A.N.); (S.I.); (A.B.); (K.C.)
| | - Anurag Dutta Chaudhury
- Department of Haematology, Christian Medical College, Vellore 632004, India; (J.R.); (A.D.C.); (D.R.)
| | - Debanjan Roy
- Department of Haematology, Christian Medical College, Vellore 632004, India; (J.R.); (A.D.C.); (D.R.)
- Manipal Academy of Higher Education, Manipal 576119, India
| | - Karthik Chambayil
- Center for Stem Cell Research (A Unit of InStem, Bengaluru, India), Christian Medical College, Vellore 632002, India; (A.N.); (S.I.); (A.B.); (K.C.)
| | - Jyoti Singh
- National Centre for Cell Science, University of Pune Campus, Pune 411007, India;
| | - Yukio Nakamura
- Cell Engineering Division, RIKEN BioResource Research Center, Ibaraki 305-0074, Japan;
| | - Shaji R. Velayudhan
- Center for Stem Cell Research (A Unit of InStem, Bengaluru, India), Christian Medical College, Vellore 632002, India; (A.N.); (S.I.); (A.B.); (K.C.)
- Department of Haematology, Christian Medical College, Vellore 632004, India; (J.R.); (A.D.C.); (D.R.)
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50
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Dou B, Zhou H, Hong Y, Zhao L, Wang P. Cross-triggered and cascaded recycling amplification system for electrochemical detection of circulating microRNA in human serum. Chem Commun (Camb) 2021; 57:7116-7119. [PMID: 34179904 DOI: 10.1039/d1cc02060a] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
A cross-triggered and cascaded recycling amplification system was developed for electrochemical sensing of microRNA 122 based on the DNAzyme/multicomponent nucleic acid enzyme cleavage technique and a dumbbell-shaped probe. The linear range and detection limit were obtained to be 1 fM-100 pM and 0.34 fM, respectively. Compared with some reported studies, the proposed system can achieve the selective detection of endogenous miRNA in liver injury patients and healthy human serums with the advantages of high sensitivity, low cost, and easy manipulation, which are significant for disease diagnosis as well as the fundamental research of molecular biology.
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Affiliation(s)
- Baoting Dou
- School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
| | - Hui Zhou
- School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
| | - Yajun Hong
- School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
| | - Liming Zhao
- School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
| | - Po Wang
- School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
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