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Zhang F, Geng L, Zhang J, Han S, Guo M, Xu Y, Chen C. miR-486-5p diagnosed atrial fibrillation, predicted the risk of left atrial fibrosis, and regulated angiotensin II-induced cardiac fibrosis via modulating PI3K/Akt signaling through targeting FOXO1. Mol Cell Biochem 2025; 480:1077-1087. [PMID: 38782834 DOI: 10.1007/s11010-024-05027-8] [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: 12/06/2023] [Accepted: 05/04/2024] [Indexed: 05/25/2024]
Abstract
This study focused on miR-486-5p in atrial fibrillation (AF) evaluating its clinical significance and revealing its regulatory mechanism in cardiac fibroblasts, aiming to explore a novel biomarker for AF. The study enrolled 131 AF patients and 77 non-AF individuals. With the help of polymerase chain reaction (PCR), the expression of miR-486-5p was evaluated. The significance of miR-486-5p in the diagnosis of AF and the occurrence of left atrial fibrosis (LAF) was assessed by receiver operating curve (ROC) and logistic analyses. The regulatory effect and mechanism of miR-486-5p on cardiac fibrosis were investigated in human cardiac fibroblasts treated with angiotensin II. miR-486-5p was significantly upregulated in AF patients and discriminated AF patients from non-AF individuals. Increasing miR-486-5p showed a significant association with decreasing left ventricular ejection fraction (LVEF), increasing left atrial diameter (LAD) and left ventricular end-diastolic diameter (LVEDd), and the high incidence of LAF in AF patients. Moreover, miR-486-5p was identified as a risk factor for LAF and could distinguish AF patients with LAF and without LAF. In cardiac fibroblasts, angiotensin II induced the upregulation of miR-486-5p and promoted cell proliferation, migration, and collagen synthesis. miR-486-5p negatively regulated forkhead box O1 (FOXO1) and its knockdown could reverse the promoted effect of angiotensin II. FOXO1 alleviated the effect of miR-486-5p, and the miR-486-5p/FOXO1 could activate PI3K/Akt signaling. The activation of PI3K/Akt signaling alleviated the enhanced proliferation, migration, and collagen synthesis of cardiac fibroblasts induced by angiotensin II, and its inhibition showed opposite effects. Increased miR-486-5p served as a biomarker for the diagnosis and development prediction of AF. miR-486-5p regulated cardiac fibroblast viability and collagen synthesis via modulating the PI3K/Akt signaling through targeting FOXO1.
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Affiliation(s)
- Fang Zhang
- Department of Cardiology, Affiliated Hospital of Hebei University, No. 212, Yuhua East Road, Baoding, 071000, People's Republic of China
| | - Lu Geng
- Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China
| | - Jing Zhang
- Department of Cardiology, Affiliated Hospital of Hebei University, No. 212, Yuhua East Road, Baoding, 071000, People's Republic of China
| | - Siliang Han
- Department of Cardiology, Affiliated Hospital of Hebei University, No. 212, Yuhua East Road, Baoding, 071000, People's Republic of China
| | - Mengya Guo
- Department of Cardiology, Affiliated Hospital of Hebei University, No. 212, Yuhua East Road, Baoding, 071000, People's Republic of China
| | - Yaxin Xu
- Department of Cardiology, Affiliated Hospital of Hebei University, No. 212, Yuhua East Road, Baoding, 071000, People's Republic of China
| | - Chunhong Chen
- Department of Cardiology, Affiliated Hospital of Hebei University, No. 212, Yuhua East Road, Baoding, 071000, People's Republic of China.
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Vastrad B, Vastrad C. Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next-generation sequencing data analysis. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2024; 25:116. [DOI: 10.1186/s43042-024-00572-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 08/23/2024] [Indexed: 01/04/2025] Open
Abstract
Abstract
Background
Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis.
Methods
Next-generation sequencing dataset GSE243039 was obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein–protein interaction (PPI) network was constructed and modules were analyzed using the Human Integrated Protein–Protein Interaction rEference database and Cytoscape software, and hub genes were identified. Subsequently, a network between miRNAs and hub genes, and network between TFs and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve analysis was used to validate the hub genes.
Results
A total of 958 DEGs, including 479 upregulated genes and 479 downregulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including vcam1, snca, prkcb, adrb2, foxq1, mdfi, actbl2, prkd1, dapk1 and actc1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including tcf3 (transcription factor 3) and clock (clock circadian regulator), were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network.
Conclusions
This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment and monitoring of endometriosis.
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Kluz N, Kowalczyk E, Wasilewska M, Gil-Kulik P. Diagnostic Value and Molecular Function of MicroRNAs in Endometrial Diseases: A Systematic Review. Cancers (Basel) 2024; 16:2416. [PMID: 39001478 PMCID: PMC11240806 DOI: 10.3390/cancers16132416] [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: 05/28/2024] [Revised: 06/21/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
The human endometrium experiences significant cyclic morphological and biochemical changes throughout the menstrual cycle to prepare for embryo implantation. These processes are meticulously regulated by ovarian steroids and various locally expressed genes, encompassing inflammatory reactions, apoptosis, cell proliferation, angiogenesis, differentiation (tissue formation), and tissue remodeling. MicroRNAs (miRNAs) have been recognized as crucial regulators of gene expression, with their altered expression being linked to the onset and progression of various disorders, including cancer. This review examines the expression of miRNAs in the endometrium and their potential regulatory roles under pathological conditions such as endometriosis, recurrent implantation failure and endometrial cancer. Given miRNAs' critical role in maintaining gene expression stability, understanding the regulatory mechanisms of endometrial miRNAs and identifying their specific target genes could pave the way for developing preventive and therapeutic strategies targeting specific genes associated with these reproductive disorders.
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Affiliation(s)
- Natalia Kluz
- Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str., 20-080 Lublin, Poland;
| | - Emilia Kowalczyk
- Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str., 20-080 Lublin, Poland;
| | - Małgorzata Wasilewska
- Department of Physical Chemistry, Institute of Chemical Sciences, Maria Curie-Sklodowska University, Maria Curie-Sklodowska Sq. 3, 20-031 Lublin, Poland;
| | - Paulina Gil-Kulik
- Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str., 20-080 Lublin, Poland;
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Jin Q, Liu C, Cao Y, Wang F. miR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1. BMC Immunol 2024; 25:33. [PMID: 38834979 DOI: 10.1186/s12865-024-00624-0] [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: 03/25/2024] [Accepted: 05/21/2024] [Indexed: 06/06/2024] Open
Abstract
PURPOSE Severe community-acquired pneumonia (SCAP) is a common respiratory system disease with rapid development and high mortality. Exploring effective biomarkers for early detection and development prediction of SCAP is of urgent need. The function of miR-486-5p in SCAP diagnosis and prognosis was evaluated to identify a promising biomarker for SCAP. PATIENTS AND METHODS The serum miR-486-5p in 83 patients with SCAP, 52 healthy individuals, and 68 patients with mild CAP (MCAP) patients were analyzed by PCR. ROC analysis estimated miR-486-5p in screening SCAP, and the Kaplan-Meier and Cox regression analyses evaluated the predictive value of miR-486-5p. The risk factors for MCAP patients developing SCAP were assessed by logistic analysis. The alveolar epithelial cell was treated with Klebsiella pneumonia to mimic the occurrence of SCAP. The targeting mechanism underlying miR-486-5p was evaluated by luciferase reporter assay. RESULTS Upregulated serum miR-486-5p screened SCAP from healthy individuals and MCAP patients with high sensitivity and specificity. Increasing serum miR-486-5p predicted the poor outcomes of SCAP and served as a risk factor for MCAP developing into SCAP. K. pneumonia induced suppressed proliferation, significant inflammation and oxidative stress in alveolar epithelial cells, and silencing miR-486-5p attenuated it. miR-486-5p negatively regulated FOXO1, and the knockdown of FOXO1 reversed the effect of miR-486-5p in K. pneumonia-treated alveolar epithelial cells. CONCLUSION miR-486-5p acted as a biomarker for the screening and monitoring of SCAP and predicting the malignancy of MCAP. Silencing miR-486-5p alleviated inflammation and oxidative stress induced by K. pneumonia via negatively modulating FOXO1.
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Affiliation(s)
- Qianqi Jin
- Department of Clinic Laboratory, The Sixth Hospital of Wuhan Affiliated Hospital of Jianghan University, Wuhan, 430015, China
| | - Chuanlan Liu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug, and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yan Cao
- Department of Emergency Medical, Shanghai Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, 200233, China
| | - Feiyan Wang
- Department of Emergency Medical, Shanghai Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, 200233, China.
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Zhu G, Jiang L, Tan K, Li Y, Hu M, Zhang S, Liu Z, Li L. MSCs-derived exosomes containing miR-486-5p attenuate cerebral ischemia and reperfusion (I/R) injury. Gene 2024; 906:148262. [PMID: 38346456 DOI: 10.1016/j.gene.2024.148262] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 01/29/2024] [Accepted: 02/06/2024] [Indexed: 02/16/2024]
Abstract
OBJECTIVES This study aims to investigate the impact of mesenchymal stem cell (MSC)-derived exosomes (Exo) on cerebral ischemia and reperfusion (I/R) injury, along with the underlying mechanism. METHODS An animal model of cerebral ischemia was induced using middle cerebral artery occlusion (MCAO), and a cell model utilizing Neuro-2a cells was established through oxygen-glucose deprivation/reoxygenation (OGD/R). Exosomes isolated from mouse MSCs were administered to mice or used to stimulate Neuro-2a cells. Exosomes from MSCs transfected with miR-NC, miR-486-5p mimics, miR-486-5p inhibitor, or phosphatase and tensin homolog (PTEN) short hairpin RNAs (sh-PTEN) were employed to stimulate Neuro-2a cells. The regulatory axis of miR-486-5p and PTEN was confirmed through rescue experiments. RESULTS Exo-miR-486-5p mimics alleviated cerebral I/R injury, improving neurological deficits and reducing the infarct ratio. Furthermore, Exo-miR-486-5p mimics attenuated OGD/R-induced defects in cell viability and inhibited apoptosis in Neuro-2a cells. These mimics also reduced levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA) while enhancing superoxide dismutase (SOD) activity, both in brain tissue homogenates of mice and cell supernatants. Mechanistically, PTEN was identified as a target of miR-486-5p, and the downregulation of PTEN notably elevated Exo-miR-486-inhibitor-induced reductions in cell viability while mitigating cell apoptosis. CONCLUSION The results of this study demonstrate the potential of exosomes derived from MSCs to protect against cerebral I/R injury via the miR-486-5p and PTEN axis.
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Affiliation(s)
- Genbao Zhu
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China
| | - La Jiang
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China
| | - Kemeng Tan
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China
| | - Yafen Li
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China
| | - Mengxue Hu
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China
| | - Shengnan Zhang
- The Department of Neurosurgery, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China
| | - Zhenlin Liu
- The Department of Neurosurgery, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China
| | - Lili Li
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China.
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Zhang H, Liu D, Fan X. Diagnostic and prognostic significance of miR-486-5p in patients who underwent minimally invasive surgery for lumbar spinal stenosis. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2024; 33:1979-1985. [PMID: 38528160 DOI: 10.1007/s00586-024-08203-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/29/2024] [Accepted: 02/22/2024] [Indexed: 03/27/2024]
Abstract
BACKGROUND This study aimed to investigate the expression and clinical value of microRNA miR-486-5p in diagnosing lumbar spinal stenosis (LSS) patients and predicting the clinical outcomes after minimally invasive spinal surgery (MISS) in LSS patients, and the correlation of miR-486-5p with inflammatory responses in LSS patients. METHODS This study included 52 LSS patients, 46 patients with lumbar intervertebral disk herniation (LDH) and 42 healthy controls. Reverse transcription quantitative PCR was used to detect miR-486-5p expression. The ability of miR-486-5p to discriminate between different groups was evaluated by receiver-operating characteristic analysis. The visual analogue scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopaedic Association (JOA) scores at 6 months postoperatively were used to reflect the clinical outcomes of LSS patients. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factor [interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)]. The correlation of miR-486-5p with continuous variables in LSS patients was evaluated by the Pearson correlation coefficient. RESULTS Expression of serum miR-486-5p was upregulated in LSS patients and had high diagnostic value to screen LSS patients. In addition, serum miR-486-5p could predict the 6-month clinical outcomes after MISS therapy in LSS patients. Moreover, serum miR-486-5p was found to be positively correlated with the levels of IL-1β and TNF-α in patients with LSS. CONCLUSION miR-486-5p, increased in LSS patients, can function as an indicator to diagnose LSS and a predictive indicator for the clinical outcomes after MISS therapy in LSS patients. In addition, miR-486-5p may regulate LSS progression by modulating inflammatory responses.
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Affiliation(s)
- Heqing Zhang
- The Second Department of Spine Surgery, Yantaishan Hospital, Yantai, 264003, Shandong, China
| | - Dong Liu
- The Second Department of Spine Surgery, Yantaishan Hospital, Yantai, 264003, Shandong, China
| | - Xiaoguang Fan
- The Second Department of Spine Surgery, Yantaishan Hospital, Yantai, 264003, Shandong, China.
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Hayashi Y, Kimura S, Yano E, Yoshimoto S, Saeki A, Yasukochi A, Hatakeyama Y, Moriyama M, Nakamura S, Jimi E, Kawakubo-Yasukochi T. Id4 modulates salivary gland homeostasis and its expression is downregulated in IgG4-related disease via miR-486-5p. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119404. [PMID: 36535369 DOI: 10.1016/j.bbamcr.2022.119404] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/09/2022] [Accepted: 11/23/2022] [Indexed: 12/23/2022]
Abstract
Salivary glands are physiologically orchestrated by the coordinated balance between cell differentiation, proliferation, apoptosis, and interactions between epithelial, mesenchymal endothelial, and neuronal cells, and they are frequent sites of manifestations of Sjögren's syndrome (SS) or IgG4-related disease (IgG4-RD). However, little is known about salivary gland homeostasis and its involvement in those diseases. Inhibitor of DNA binding/differentiation 4 (Id4) is an Id protein involved in the transcriptional control of many biological events, including differentiation. Studies of Id4-deficient mice revealed that Id4-deficient submandibular glands were smaller and exhibited accelerated differentiation, compared with those from wild-type littermates. In addition, dry mouth symptoms and Th17 expansion in splenocytes were also observed in the absence of Id4. Furthermore, Id4 levels in the salivary glands of patients with IgG4-RD, but not SS, were significantly decreased compared with those of healthy controls. miRNA-mRNA integrated analysis demonstrated that miR-486-5p was upregulated in IgG4-RD patients and that it might regulate Id4 in the lesion sites. Together, these results provide evidence for the inhibitory role of Id4 in salivary differentiation, and a critical association between Id4 downregulation and IgG4-RD.
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Affiliation(s)
- Yoshikazu Hayashi
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Division of Functional Structure, Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan
| | - Soi Kimura
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Ena Yano
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Shohei Yoshimoto
- Section of Pathology, Department of Morphological Biology, Division of Biomedical Sciences, Fukuoka Dental College, Fukuoka 814-0193, Japan; Oral Medicine Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan
| | - Ayaka Saeki
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Atsushi Yasukochi
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Yuji Hatakeyama
- Division of Functional Structure, Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan
| | - Masafumi Moriyama
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Seiji Nakamura
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Eijiro Jimi
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Tomoyo Kawakubo-Yasukochi
- OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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Thakur L, Thakur S. The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions. Front Endocrinol (Lausanne) 2023; 14:1166948. [PMID: 37152960 PMCID: PMC10161733 DOI: 10.3389/fendo.2023.1166948] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/07/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction Endometrial cancer is a hormone-dependent malignancy, and sex steroid hormones play a crucial role in its pathogenesis. Recent studies have demonstrated that microRNAs (miRNAs) can regulate the expression of sex steroid hormone receptors and modulate hormone signaling pathways. Our aim is to provide an overview of the current understanding of the role of miRNAs in endometrial cancer regulated by sex steroid hormone pathways. Methods A thorough literature search was carried out in the PubMed database. The articles published from 2018 to the present were included. Keywords related to miRNAs, endometrial cancer, and sex steroid hormones were used in the search. Results Dysregulation of miRNAs has been linked to abnormal sex steroid hormone signaling and the development of endometrial cancer. Various miRNAs have been identified as modulators of estrogen and progesterone receptor expression, and the miRNA expression profile has been shown to be a predictor of response to hormone therapy. Additionally, specific miRNAs have been implicated in the regulation of genes involved in hormone-related signaling pathways, such as the PI3K/Akt/mTOR and MAPK/ERK pathways. Conclusion The regulation of sex steroid hormones by miRNAs is a promising area of research in endometrial cancer. Future studies should focus on elucidating the functional roles of specific miRNAs in sex steroid hormone signaling and identifying novel miRNA targets for hormone therapy in endometrial cancer management.
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Affiliation(s)
- Lovlesh Thakur
- Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sunil Thakur
- Origin LIFE Healthcare Solutions and Research Center, Chandigarh, India
- *Correspondence: Sunil Thakur,
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Yen TA, Huang HC, Wu ET, Chou HW, Chou HC, Chen CY, Huang SC, Chen YS, Lu F, Wu MH, Tsao PN, Wang CC. Microrna-486-5P Regulates Human Pulmonary Artery Smooth Muscle Cell Migration via Endothelin-1. Int J Mol Sci 2022; 23:ijms231810400. [PMID: 36142307 PMCID: PMC9499400 DOI: 10.3390/ijms231810400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/05/2022] [Accepted: 09/07/2022] [Indexed: 11/30/2022] Open
Abstract
Pulmonary arterial hypertension (PAH) is a fatal or life-threatening disorder characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance. Abnormal vascular remodeling, including the proliferation and phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs), represents the most critical pathological change during PAH development. Previous studies showed that miR-486 could reduce apoptosis in different cells; however, the role of miR-486 in PAH development or HPASMC proliferation and migration remains unclear. After 6 h of hypoxia treatment, miR-486-5p was significantly upregulated in HPASMCs. We found that miR-486-5p could upregulate the expression and secretion of ET-1. Furthermore, transfection with a miR-486-5p mimic could induce HPASMC proliferation and migration. We also found that miRNA-486-5p could downregulate the expression of SMAD2 and the phosphorylation of SMAD3. According to previous studies, the loss of SMAD3 may play an important role in miRNA-486-5p-induced HPASMC proliferation. Although the role of miRNA-486-5p in PAH in in vivo models still requires further investigation and confirmation, our findings show the potential roles and effects of miR-486-5p during PAH development.
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Affiliation(s)
- Ting-An Yen
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Hsin-Chung Huang
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - En-Ting Wu
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Heng-Wen Chou
- Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Hung-Chieh Chou
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Chien-Yi Chen
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Shu-Chien Huang
- Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Yih-Sharng Chen
- Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Frank Lu
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Mei-Hwan Wu
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Po-Nien Tsao
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Ching-Chia Wang
- Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Correspondence:
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Zheng X, Lv X, Zhu L, Xu K, Shi C, Cui L, Ding H. The Circadian Gene NPAS2 Act as a Putative Tumor Stimulative Factor for Uterine Corpus Endometrial Carcinoma. Cancer Manag Res 2022; 13:9329-9343. [PMID: 34992456 PMCID: PMC8711112 DOI: 10.2147/cmar.s343097] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 12/08/2021] [Indexed: 12/26/2022] Open
Abstract
Background Mounting evidence indicates altered circadian rhythm represents a critical factor affecting carcinogenesis and tumor progression. The circadian gene neuronal PAS domain protein 2 (NPAS2) constitutes a newly discovered prognostic biomarker. NPAS2 dysregulation is found in multiple malignancies, although its functions in uterine corpus endometrial carcinoma (UCEC) remain largely unknown. Objective To evaluate NPAS2’s roles in UCEC and to explore the underlying mechanisms. Methods NPAS2 transcription levels, patient prognosis, different clinical stages and target microRNAs in UCEC cases were comparatively assessed based on public databases, including UALCAN, GEPIA, TIMER, Kaplan–Meier plotter, starBase database, LinkedOmics and String. Then, qRT-PCR and immunohistochemical analysis were applied to analyze the expression of NPAS2 in UCEC tissue samples. CCK-8, clonogenic assay and flow cytometry were carried out for detecting cell viability, colony formation ability and cell apoptosis, respectively. Results NPAS2 was upregulated in tissue samples from UCEC cases compared with the corresponding control specimens. NPAS2 overexpression was associated with decreased overall (OS), disease free (DFS) and relapse free (RFS) survival in UCEC. In addition, NPAS2 overexpression was associated with clinical stage, tumor grade, estrogen receptor status, myometrial invasion in UCEC. Furthermore, NPAS2 knockdown or overexpression altered cell proliferation and apoptosis in UCEC. Moreover, NPAS2 showed significant negative correlations with miR-17-5p and miR-93-5p, and positive correlations with miR-106a-5p and miR-381-3p in UCEC. Conclusion NPAS2 overexpression is associated with poor prognosis and clinicopathological characteristics in UCEC and promotes proliferation and colony formation while inhibiting apoptosis. Finally, NPAS2 is associated with several miRNAs in UCEC.
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Affiliation(s)
- Xiaojiao Zheng
- Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People's Republic of China.,Department of Biochemistry & Genetics, The National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, People's Republic of China
| | - Xiuyi Lv
- Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People's Republic of China
| | - Linyan Zhu
- Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People's Republic of China
| | - Kejun Xu
- Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People's Republic of China
| | - Cong Shi
- Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People's Republic of China
| | - Lining Cui
- Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People's Republic of China
| | - Huiqing Ding
- Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People's Republic of China
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11
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Liu L, Xiao S, Wang Y, Zhu Z, Cao Y, Yang S, Mai R, Zheng Y. Identification of a novel circular RNA circZNF652/miR-486-5p/SERPINE1 signaling cascade that regulates cancer aggressiveness in glioblastoma (GBM). Bioengineered 2022; 13:1411-1423. [PMID: 35258403 PMCID: PMC8805984 DOI: 10.1080/21655979.2021.2018096] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 12/08/2021] [Indexed: 12/27/2022] Open
Abstract
Circular RNAs (circRNAs) are closely associated with cancer development in glioblastoma (GBM), and this study aims to explore the molecular mechanisms of a novel circular RNA circZNF652 in regulating GBM aggressiveness. The present study found that CircZNF652 and SERPINE1 were upregulated, while miR-486-5p was downregulated in GBM tissues and cell lines, and GBM patients with high expression of CircZNF652 and SERPINE1, and patients with low expression of miR-486-5p tended to have a worse prognosis. Further results validated that both silencing of circZNF652 and miR-486-5p overexpression suppressed cell growth, migration, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis in GBM cells in vitro and in vivo. Next, the underlying mechanisms were investigated, and we found that circZNF652 sponged miR-486-5p to upregulate SERPINE1 in GBM cells. Also, we validated that knock-down of circZNF652 regulated the miR-486-5p/SERPINE1 axis to reverse the malignant phenotypes in GBM cells. Interestingly, we noticed that GBM cells derived exosomes were characterized by high-expressed CircZNF652. Collectively, we concluded that targeting the circular RNA circZNF652/miR-486-5p/SERPINE1 axis was a novel and effective strategy to suppress cancer progression in GBM.
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Affiliation(s)
- Liang Liu
- Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
| | - Shan Xiao
- Department of Endocrinology, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
| | - Yan Wang
- Department of General Practice Medicine, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
| | - Zifeng Zhu
- Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
| | - Yiyao Cao
- Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
| | - Sen Yang
- Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
| | - Rongkang Mai
- Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
| | - Yong Zheng
- Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen, Guang Dong, China
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12
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Liao L, Chen Y, Zhou J, Ye J. MicroRNA-133b Inhibits nTumor Cell Proliferation, Migration and Invasion by Targeting SUMO1 in Endometrial Carcinoma. Technol Cancer Res Treat 2021; 20:15330338211065241. [PMID: 34918563 PMCID: PMC8721366 DOI: 10.1177/15330338211065241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Objectives: An increasing number of studies have confirmed that microRNAs (miRNAs/miRs), as oncogenes or tumor suppressor genes, play an important regulatory role in the occurrence and development of numerous types of cancer. The aim of the present study was to investigate the potential role and mechanism of miR-133b and small ubiquitin like modifier 1 (SUMO1) in the development of endometrial carcinoma (EC). Methods: First, Venn diagrams are used to identify the differential expressions of miRNAs in EC from GSE35794 and GSE25405 datasets. Next, we conduct a series of functional tests, including Cell Counting Kit-8, wound healing, and transwell and matrigel assays. Then, a bioinformatics tool, is used to identify downstream target genes of miR-133b and to verify the predicted results by RT-qPCR, Western blotting and double luciferase reporter gene analysis. Finally, in order to further study whether the cellular function of miR-133b is mediated by the expression of SUMO1, rescue experiments were carried out. Results: The results of bioinformatics studies showed that the expression of miR-133b was down-regulated in EC tissues, and the expression level of miR-133b was lower in patients with high grade, different histology or menopausal status. The results of functional assay showed that overexpression of miR-133b reduced cell proliferation, migration and invasion. On the contrary, miR-133b silence has the opposite effect. SUMO1 was the direct target of miR-133b and was negatively regulated by miR-133b. The decrease of SUMO1mRNA expression inhibited the proliferation, migration and invasion of EC cells, and reversed the effect of miR-133b on EC cells. Conclusion: The findings from the present study suggested that miR-133b may be a tumor suppressor gene and a potential therapeutic target for the treatment of EC.
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Affiliation(s)
- Lingyun Liao
- 477808First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Yun Chen
- 477808First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jieli Zhou
- 477808First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jing Ye
- School of Clinical Medicine, 74582Jiangxi University of Traditional Chinese Medicine, Nanchang, China
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13
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Lu J, Liang J, Xu M, Wu Z, Cheng W, Wu J. Identification of an eleven-miRNA signature to predict the prognosis of endometrial cancer. Bioengineered 2021; 12:4201-4216. [PMID: 34338136 PMCID: PMC8806668 DOI: 10.1080/21655979.2021.1952051] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Endometrial cancer (EC) is the most common gynecological malignancy. Recent studies have uncovered miRNA acted a striking role in predicting the prognosis of multiple tumors. Over 500 EC samples were selected from the Cancer Genome Atlas (TCGA) database. Univariate, LASSO and multivariate Cox regression analysis were employed to screen out the prognosis-involved miRNAs. Kaplan-Meier (K-M) and time-dependent receiver operation characteristic (ROC) curves were conducted to reveal survival analysis and assess the accuracy of the signature. The independence of the model was verified via univariate and multivariate Cox regression analysis. Besides, qRT-PCR was conducted to testified the expression of 11 miRNAs in 16 paired tissues. A total of 514 specimens were randomly divided into the training set and the testing set, then an 11 miRNAs-based signature were determined which divided the patients into high-risk group and low-risk group. The survival was markedly different and the ROC curve exhibited a precise prediction. Meanwhile, the univariate and multivariate Cox regression analysis verified the miRNAs-based model was an independent indicator of EC. Moreove, the prediction ability of this model with clinicopathological features was more efficient. Finally, functional enrichment analysis demonstrated these miRNAs were associated with the occurrence and progression of cancer. Additionally, hsa-mir-216b, hsa-mir-363, hsa-mir-940 and hsa-mir-1301 were highly expressed in EC tissues in contrast to normal tissues through qRT-PCR. Importantly, the eleven-miRNA signature was full of robust ability to predict the prognosis of EC.
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Affiliation(s)
- Jing Lu
- State Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Jiangsu Women and Children Health Hospital, Nanjing, China
| | - Jianqiang Liang
- Department of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu province, China
| | - Mengting Xu
- Department of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu province, China
| | - Zhipeng Wu
- Department of Urology, the Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing 221116, Jiangsu province, China
| | - Wenjun Cheng
- Department of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu province, China
| | - Jie Wu
- State Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Jiangsu Women and Children Health Hospital, Nanjing, China
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14
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Sun B, Guo S. miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes. J Inflamm Res 2021; 14:3687-3695. [PMID: 34354365 PMCID: PMC8331108 DOI: 10.2147/jir.s323433] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/08/2021] [Indexed: 12/17/2022] Open
Abstract
Background As a molecular detection method, miRNA can quickly diagnose and prevent diseases, intervene in disease as early as possible, and reduce mortality. This study was to investigate the potential clinical diagnostic and predictive significance of miR-486-5p in sepsis and its correlation with inflammation and disease severity. Methods The serum miR-486-5p in 108 sepsis, 60 pneumonia-infected, and 101 healthy controls were detected by RT-qPCR. Spearman coefficient detects the correlation between serum miRNA and disease severity indicators (APACHE II, SOFA scores), and inflammation indicators (CRP, PCT), respectively. The diagnostic significance of miR-486-5p in sepsis was analyzed by the ROC curve. Kaplan–Meier estimator and Cox regression hazards analysis of the predictive significance of serum miR-486-5p in 28-day survival from sepsis. Results Serum miR-486-5p was increased in sepsis patients compared with healthy control and pneumonia-infected patients (P < 0.001). And increased serum miR-486-5p was positively associated with disease severity (SOFA score and APACHE II score) and inflammation (CRP and PCT). Serum miR-486-5p can not only identify sepsis patients from healthy controls (AUC = 0.914) but also significantly distinguish sepsis patients from pneumonia-infected patients (AUC = 0.814), showing good potential as a diagnostic biomarker for sepsis. In addition, serum miR-486-5p was an independent predictor of 28-day survival (log-rank P = 0.012), and patients with high levels of miR-486-5p had a poorer overall 28-day survival (HR = 3.057, 95% CI = 1.385–17.817, P = 0.014). Conclusion miR-486-5p is a potential diagnostic biomarker for sepsis, and its high level is significantly correlated with the disease severity and inflammation. In addition, miR-486-5p were predictive risk factors for 28-day survival in sepsis patients.
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Affiliation(s)
- Baobin Sun
- Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, 100020, People's Republic of China
| | - Shubin Guo
- Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing, 100020, People's Republic of China
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15
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Klicka K, Grzywa TM, Klinke A, Mielniczuk A, Włodarski PK. The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis-A Systematic Review. Cancers (Basel) 2021; 13:3393. [PMID: 34298609 PMCID: PMC8304659 DOI: 10.3390/cancers13143393] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/18/2021] [Accepted: 07/02/2021] [Indexed: 12/17/2022] Open
Abstract
Endometrial cancer (EC) is the most common genital cancer in women with increasing death rates. MiRNAs are short non-coding RNAs that regulate gene expression on the post-transcriptional levels. Multiple studies demonstrated a fundamental role of miRNAs in the regulation of carcinogenesis. This systematic review is a comprehensive overview of the role of miRNAs in the regulation of cancer cell invasiveness and metastasis in EC. The literature was searched for studies investigating the role of miRNAs in the regulation of invasiveness and metastasis in EC. We explored PubMed, Embase, and Scopus using the following keywords: miRNA, metastasis, invasiveness, endometrial cancer. Data were collected from 163 articles that described the expression and role of 106 miRNAs in the regulation of EC invasiveness and metastasis out of which 63 were tumor suppressor miRNAs, and 38 were oncomiRNAs. Five miRNAs had a discordant role in different studies. Moreover, we identified 66 miRNAs whose expression in tumor tissue or concentration in serum correlated with at least one clinical parameter. These findings suggest a crucial role of miRNAs in the regulation of EC invasiveness and metastasis and present them as potential prognostic factors for patients with EC.
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Affiliation(s)
- Klaudia Klicka
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (T.M.G.); (A.K.); (A.M.)
- Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Tomasz M. Grzywa
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (T.M.G.); (A.K.); (A.M.)
- Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
- Department of Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Alicja Klinke
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (T.M.G.); (A.K.); (A.M.)
| | - Aleksandra Mielniczuk
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (T.M.G.); (A.K.); (A.M.)
| | - Paweł K. Włodarski
- Department of Methodology, Medical University of Warsaw, 02-091 Warsaw, Poland; (K.K.); (T.M.G.); (A.K.); (A.M.)
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16
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Yang LJ, Gao L, Guo YN, Liang ZQ, Li DM, Tang YL, Liu YH, Gao WJ, Zeng JJ, Shi L, Wei KL, Chen G. Upregulation of microRNA miR-141-3p and its prospective targets in endometrial carcinoma: a comprehensive study. Bioengineered 2021; 12:2941-2956. [PMID: 34180758 PMCID: PMC8806562 DOI: 10.1080/21655979.2021.1943111] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The clinicopathological value of microRNA-141-3p (miR-141-3p) and its prospective target genes in endometrial carcinoma (EC) remains unclear. The present study determined the expression level of miR-141-3p in EC via quantitative real-time PCR (RT-qPCR). RT-qPCR showed a markedly higher expression level of miR-141-3p in EC tissues than in non-EC endometrium tissues (P < 0.0001). The microarray and miRNA-seq data revealed upregulation of miR-141-3p. Integrated analysis based on 675 cases of EC and 63 controls gave a standardized mean difference of 1.737, confirmed the upregulation of miR-141-3p. The Kaplan-Meier survival curve showed that a higher expression of miR-141-3p positively corelated with a poorer prognosis. Combining the predicted targets and downregulated genes in EC, we obtained 271 target genes for miR-141-3p in EC. Two potential targets, PPP1R12A and PPP1R12B, were downregulated at both the mRNA and protein levels. This study indicates that the overexpression of miR-141-3p may play an important part in the carcinogenesis of EC. The overexpression of miR-141-3p may be a risk factor for the prognosis of patients with EC.
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Affiliation(s)
- Lin-Jie Yang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Li Gao
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Yi-Nan Guo
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Zi-Qian Liang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Dong-Ming Li
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Yu-Lu Tang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Yi-Hong Liu
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Wan-Jing Gao
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Jing-Jing Zeng
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Lin Shi
- Department of Pathology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Kang-Lai Wei
- Department of Pathology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
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17
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Wang H, Yang Q, Li J, Chen W, Jin X, Wang Y. MicroRNA-15a-5p inhibits endometrial carcinoma proliferation, invasion and migration via downregulation of VEGFA and inhibition of the Wnt/β-catenin signaling pathway. Oncol Lett 2021; 21:310. [PMID: 33732386 PMCID: PMC7905532 DOI: 10.3892/ol.2021.12570] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 12/16/2020] [Indexed: 02/07/2023] Open
Abstract
Endometrial carcinoma (EC) is one of the most common malignant gynecological tumors. Dysregulation of microRNAs (miRNAs/miRs) is frequently identified in human tumors, playing key regulatory roles in tumor growth and metastasis. The present study aimed to explore the functions and potential mechanisms of miR-15a-5p in EC progression. RT-qPCR was used to detect the expression levels of miR-15a-5p and vascular endothelial growth factor A (VEGFA) mRNA. Western blot analysis was performed to examine the expression of related proteins. Functional assays, including proliferation and Transwell assays were performed to determine the roles of miR-15a-5p in EC progression. TargetScan and luciferase reporter assays were used to explore the potential target genes of miR-15a-5p. The results revealed that miR-15a-5p was underexpressed in EC tissue samples in comparison with that in matched normal tissue samples. The expression level of miR-15a-5p was associated with the clinicopathologic characteristics of EC patients. Notably, both in vitro and in vivo assays revealed that miR-15a-5p upregulation significantly inhibited EC growth and metastasis. Furthermore, bioinformatics analysis and dual luciferase reporter assay indicated that VEGFA was a candidate target of miR-15a-5p. Mechanistic investigation revealed that miR-15a-5p inhibited EC development via regulation of Wnt/β-catenin pathway and targeting of VEGFA. In summary, the present results demonstrated that miR-15a-5p could inhibit EC development and may serve as a promising therapeutic biomarker in EC.
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Affiliation(s)
- Honggang Wang
- Department of Clinical Laboratory, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
| | - Qingju Yang
- Department of Gynaecology, Linyi People's Hospital, Dezhou, Shandong 251500, P.R. China
| | - Jieping Li
- Department of Anesthesiology, Qingdao Hospital of Traditional Chinese Medicine, Qingdao University, Qingdao, Shandong 266033, P.R. China
| | - Wenping Chen
- Department of Cardiothoracic Surgery, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China
| | - Xiao Jin
- Department of Rehabilitation Medicine, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China
| | - Yaowen Wang
- Department of Clinical Laboratory, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
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18
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Du Z, Wang L, Xia Y. Circ_0015756 promotes the progression of ovarian cancer by regulating miR-942-5p/CUL4B pathway. Cancer Cell Int 2020; 20:572. [PMID: 33292255 PMCID: PMC7694308 DOI: 10.1186/s12935-020-01666-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 11/19/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Ovarian cancer (OC) is the gynecologic cancer with the highest mortality. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism. METHODS The levels of circ_0015756, microRNA-942-5p (miR-942-5p) and Cullin 4B (CUL4B) were determined by quantitative real-time PCR (qRT-PCR) or Western blot assay. Cell proliferation, apoptosis, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and transwell assay. The levels of proliferation-related and metastasis-related proteins were measured by Western blot assay. The relationship between miR-942-5p and circ_0015756 or CUL4B was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft assay was used to analyze tumor growth in vivo. RESULTS Circ_0015756 and CUL4B levels were increased, while miR-942-5p level was decreased in OC tissues and cells. Depletion of circ_0015756 suppressed proliferation, migration and invasion and promoted apoptosis in OC cells. Down-regulation of circ_0015756 hindered OC cell progression via modulating miR-942-5p. Also, up-regulation of miR-942-5p impeded OC cell development by targeting CUL4B. Mechanistically, circ_0015756 up-regulated CUL4B via sponging miR-942-5p. Moreover, circ_0015756 silencing inhibited tumor growth in vivo. CONCLUSION Knockdown of circ_0015756 suppressed OC progression via regulating miR-942-5p/CUL4B axis, suggesting that circ_0015756 might be a potential therapeutic target for ovarian cancer.
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Affiliation(s)
- Zhenhua Du
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Heping District, Shenyang City, 110021, Liaoning Province, China.
| | - Lei Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Heping District, Shenyang City, 110021, Liaoning Province, China
| | - Yu Xia
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Heping District, Shenyang City, 110021, Liaoning Province, China
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