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Jin G, Guo T, Liu JW, Yang HY, Xu JG, Pang Y, Yang Y, He SE, Yi K. The relationship of miR-155 host gene polymorphism in the susceptibility of cancer: a systematic review and meta-analysis. Front Genet 2025; 16:1517513. [PMID: 40115820 PMCID: PMC11922843 DOI: 10.3389/fgene.2025.1517513] [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: 10/26/2024] [Accepted: 01/27/2025] [Indexed: 03/23/2025] Open
Abstract
Background miR-155 is overexpressed in many cancers, highlighting its potential as a biomarker for cancer diagnosis, treatment, and therapeutic evaluation. miR-155 is processed from the miR-155 host gene (MIR155HG). Genetic variations in MIR155HG may influence cancer susceptibility, but existing evidence is inconclusive. This study aimed to evaluate the association of MIR155HG polymorphisms with cancer risk. Material/Methods A systematic literature search identified 15 case-control studies on three single nucleotide polymorphisms (SNPs): rs767649 (T > A), rs928883 (G > A), and rs1893650 (T > C). Meta-analysis was performed using RevMan 5.4, with odds ratios (ORs) and 95% confidence intervals (CIs) as effect measures. Results No significant association was observed for rs767649 and rs928883 in overall cancer analysis. However, subgroup analysis revealed rs767649 increased susceptibility to respiratory, digestive, and reproductive cancers, while reducing cancer risk after excluding reproductive cancers. rs928883 showed a protective effect for digestive cancers. rs1893650 was not significantly associated with cancer risk. Conclusion MIR155HG polymorphisms influence susceptibility to specific cancer subtypes, particularly respiratory and digestive cancers. These findings underscore the importance of genetic and environmental factors in cancer risk and warrant further investigation.
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Affiliation(s)
- Gang Jin
- Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Tao Guo
- Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, Lanzhou, China
- The First School of Clinical Medicine of Gansu University of Chinese Medicine, Lanzhou, China
- Gansu International Scientific and Technological Cooperation Base of Diagnosis and Treatment of Congenital Heart Disease, Lanzhou, China
| | - Jia-Wei Liu
- Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Han-Yu Yang
- Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of Thoracic Surgery, Qin'an County People's Hospital, Tianshui, China
| | - Jian-Guo Xu
- Gansu International Scientific and Technological Cooperation Base of Diagnosis and Treatment of Congenital Heart Disease, Lanzhou, China
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Yao Pang
- Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Yi Yang
- Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Shao-E He
- Gansu International Scientific and Technological Cooperation Base of Diagnosis and Treatment of Congenital Heart Disease, Lanzhou, China
- The First Hospital of Lanzhou University, Lanzhou, Gansu, China
- Department of Thoracic Surgery, Kangle County Lianlu Town Health Center, Linxia, Gansu, China
| | - Kang Yi
- Department of Cardiovascular Surgery, Gansu Provincial Hospital, Lanzhou, China
- Gansu International Scientific and Technological Cooperation Base of Diagnosis and Treatment of Congenital Heart Disease, Lanzhou, China
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
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2
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Priya S, Kma L. Identification of novel microRNAs: Biomarkers for pathogenesis of hepatocellular carcinoma in mice model. Biochem Biophys Rep 2025; 41:101896. [PMID: 39881957 PMCID: PMC11774814 DOI: 10.1016/j.bbrep.2024.101896] [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: 10/24/2024] [Revised: 11/26/2024] [Accepted: 12/09/2024] [Indexed: 01/31/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the most fatal cancer that has affected both male and female populations globally. With poor diagnosis and patient survival rates, it has become a global need for scientists to come to the aid. The main objective of the study was to profile the miRNAs in the serum of Control and DEN-treated mice at different time intervals (4 Weeks, 8 Weeks, 12 Weeks, and 16 Weeks) and identify HCC-associated miRNA as putative early biomarkers along with the miRNA regulated candidate gene which may be involved in HCC. Our study group involves 4,8,12, & 16 weeks 16-week-old treated male mice. Each group was sacrificed and analyzed for the stages of HCC. We employed in silico techniques for the small RNA-Seq and bioinformatics pipeline for further analysis. Our analysis revealed over 400 differentially expressed miRNAs in each treated sample and 10 novel miRNAs. The downstream analysis of these differentially expressed miRNAs, and their target genes opened an arena of different biological processes and pathways that these miRNAs affect during the development of HCC. The work has a promising role as the miRNAs predicted through this study can be used as biomarkers for early detection of HCC.
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Affiliation(s)
- Shivani Priya
- Department of Chemistry & Biochemistry, Sharda School of Basic Sciences & Research, Sharda University, Noida, UP, India
| | - Lakhon Kma
- Department of Biochemistry, North Eastern Hill University, Shillong, India
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3
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Xu H, Huang K, Shi M, Gong H, Han M, Tian W, Wang X, Zhang D. MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application. Pharmacol Res 2024; 205:107216. [PMID: 38761883 DOI: 10.1016/j.phrs.2024.107216] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 05/20/2024]
Abstract
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
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Affiliation(s)
- Huimei Xu
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Ke Huang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Mingxuan Shi
- Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Hang Gong
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Mengyu Han
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Wenji Tian
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Xiaoying Wang
- Department of Emergency, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
| | - Dekui Zhang
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
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4
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Khan MM, Sharma V, Serajuddin M. Emerging role of miRNA in prostate cancer: A future era of diagnostic and therapeutics. Gene 2023; 888:147761. [PMID: 37666374 DOI: 10.1016/j.gene.2023.147761] [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: 04/12/2023] [Revised: 08/17/2023] [Accepted: 09/01/2023] [Indexed: 09/06/2023]
Abstract
Prostate cancer (PCa) is the most common cancer in men (20%) and is responsible for 6.8% (1/5) of all cancer-related deaths in men around the world. The development and spread of prostate cancer are driven by a wide variety of genomic changes and extensive epigenetic events. Because of this, the MicroRNA (miRNA) and associated molecular mechanisms involved in PCa genesis and aggressive were only partially identified until today. The miRNAs are a newly discovered category of regulatorsthat have recently been recognized to have a significant role in regulating numerous elements of cancer mechanisms, such as proliferation, differentiation, metabolism, and apoptosis. The miRNAs are a type of small (22-24 nucleotides), non-coding, endogenous, single-stranded RNA and work as potent gene regulators. Various types of cancer, including PCa, have found evidence that miRNA genes, which are often located in cancer-related genetic regions or fragile locations, have a role in the primary steps of tumorigenesis, either as oncogenes or tumorsuppressors. To explain the link between miRNAs and their function in the initiation and advancement of PCa, we conducted a preliminary assessment. The purpose of this research was to enhance our understanding of the connection between miRNA expression profiles and PCa by elucidating the fundamental processes of miRNA expression and the target genes.
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Affiliation(s)
- Mohd Mabood Khan
- Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India.
| | - Vineeta Sharma
- Department of Medicine, Vanderbilt University Medical Center, Nashville 37232, TN, USA
| | - Mohammad Serajuddin
- Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
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Niemira M, Erol A, Bielska A, Zeller A, Skwarska A, Chwialkowska K, Kuzmicki M, Szamatowicz J, Reszec J, Knapp P, Moniuszko M, Kretowski A. Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer. Sci Rep 2023; 13:19287. [PMID: 37935712 PMCID: PMC10630404 DOI: 10.1038/s41598-023-45317-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 10/18/2023] [Indexed: 11/09/2023] Open
Abstract
Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.
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Affiliation(s)
- Magdalena Niemira
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
| | - Anna Erol
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Agnieszka Bielska
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Anna Zeller
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Anna Skwarska
- Cancer Center, Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Karolina Chwialkowska
- Centre for Bioinformatics and Data Analysis, Medical University of Bialystok, Bialystok, Poland
| | - Mariusz Kuzmicki
- Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Bialystok, Poland
| | - Jacek Szamatowicz
- Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Bialystok, Poland
| | - Joanna Reszec
- Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland
| | - Pawel Knapp
- University Oncology Centre, University Clinical Hospital in Bialystok, Bialystok, Poland
| | - Marcin Moniuszko
- Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland
| | - Adam Kretowski
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
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6
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Tao D, Guan B, Li H, Zhou C. Expression patterns of claudins in cancer. Heliyon 2023; 9:e21338. [PMID: 37954388 PMCID: PMC10637965 DOI: 10.1016/j.heliyon.2023.e21338] [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: 12/19/2022] [Revised: 10/17/2023] [Accepted: 10/19/2023] [Indexed: 11/14/2023] Open
Abstract
Claudins are four-transmembrane proteins, which were found in tight junctions. They maintain cell barriers and regulate cell differentiation and proliferation. They are involved in maintaining cellular polarity and normal functions. Different claudins show different expression patterns. The expression level and localization of claudins are altered in various cancers. They promote or inhibit proliferation, invasion, and migration of cancer cells through multiple signaling pathways. Therefore, claudins may serve as diagnostic markers, novel therapeutic targets, and prognostic risk factors. The important roles of claudins in cancer aroused our great interest. In the present review, we provide a summary of insights into expression patterns of claudins in cancer, which is more comprehensive and provides new ideas for further research.
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Affiliation(s)
- Daoyu Tao
- Department of Pathology, The Second Hospital of Shandong University, Jinan, 250012, Shandong, China
| | - Bingxin Guan
- Department of Pathology, The Second Hospital of Shandong University, Jinan, 250012, Shandong, China
| | - Hui Li
- Department of Pathology, The Second Hospital of Shandong University, Jinan, 250012, Shandong, China
| | - Chengjun Zhou
- Department of Pathology, The Second Hospital of Shandong University, Jinan, 250012, Shandong, China
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7
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Zhu J, Jiang Q. Twist1‑mediated transcriptional activation of Claudin‑4 promotes cervical cancer cell migration and invasion. Oncol Lett 2023; 26:335. [PMID: 37427351 PMCID: PMC10326656 DOI: 10.3892/ol.2023.13921] [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: 02/18/2023] [Accepted: 05/25/2023] [Indexed: 07/11/2023] Open
Abstract
Claudin-4, a member of the claudin multigene family, participates in events associated with mesenchymal-like activity of cancerous cells. Claudin-4 expression is upregulated in cervical cancer tissue compared with that in adjoining non-neoplastic tissue. However, the mechanisms that regulate Claudin-4 expression in cervical cancer are poorly understood. Moreover, whether Claudin-4 contributes to the migration and invasion of cervical cancer cells remains unclear. By western blotting, reverse transcription-qPCR, bioinformatics analysis, dual-luciferase reporter assay, chromatin immunoprecipitation assay, wound healing assay and Transwell migration/invasion assay, the present study confirmed that Claudin-4 was a downstream target of Twist1, a helix-loop-helix transcriptional factor, the activity of which has a positive correlation with Claudin-4 expression. Mechanistically, Twist1 directly binds to Claudin-4 promoter, resulting in the transactivation of expression. The depletion of the Twist1-binding E-Box1 domain on Claudin-4 promoter via CRISPR-Cas9 knockout system downregulates Claudin-4 expression and suppresses the ability of cervical cancer cells to migrate and invade by elevating E-cadherin levels and lowering N-cadherin levels. Following activation by transforming growth factor-β, Twist1 induces Claudin-4 expression, thus enhancing migration and invasion of cervical cancer cells. In summary, the present data suggested that Claudin-4 was a direct downstream target of Twist1 and served a critical role in promoting Twist1-mediated cervical cancer cell migration and invasion.
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Affiliation(s)
- Jiaqi Zhu
- Department of Gynecology, Beilun People's Hospital, Beilun Branch of The First Affiliated Hospital, School of Medicine, Zhejiang University, Ningbo, Zhejiang 315826, P.R. China
| | - Qi Jiang
- Department of Obstetrics, Beilun People's Hospital, Beilun Branch of The First Affiliated Hospital, School of Medicine, Zhejiang University, Ningbo, Zhejiang 315826, P.R. China
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8
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Al-Moghrabi N, Al-Showimi M, Al-Yousef N, AlOtai L. MicroRNA-155-5p, Reduced by Curcumin-Re-Expressed Hypermethylated BRCA1, Is a Molecular Biomarker for Cancer Risk in BRCA1-methylation Carriers. Int J Mol Sci 2023; 24:ijms24109021. [PMID: 37240365 DOI: 10.3390/ijms24109021] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/09/2023] [Accepted: 05/17/2023] [Indexed: 05/28/2023] Open
Abstract
Constitutional BRCA1-methylation is a cancer risk factor for breast (BC) and ovarian (OC) cancer. MiR-155, regulated by BRCA1, is a multifunctional microRNA that plays a crucial role in the immune system. The present study assessed the modulation of miR-155-5p expression in peripheral white blood cells (WBCs) of BC and OC patients and cancer-free (CF) BRCA1-methylation female carriers. Additionally, we investigated the potential of curcumin to suppress miR-155-5p in BRCA1-deficient breast cancer cell lines. MiR-155-5p expression was measured using a stem-loop RT-qPCR method. Gene expression levels were determined using qRT-PCR and immunoblotting. MiR-155-5p was more highly expressed in the BRCA1-hypermethylated HCC-38 and UACC-3199 BC cell lines than in the BRCA1-mutated (HCC-1937) and WT BRCA1 (MDA-MB-321) cell lines. Curcumin suppressed miR-155-5p in the HCC-38 cells but not in the HCC-1937 cells via the re-expression of BRCA1. Elevated levels of miR-155-5p were detected in patients with non-aggressive and localized breast tumors and in patients with late-stage aggressive ovarian tumors, as well as in CF BRCA1-methylation carriers. Notably, IL2RG levels were reduced in the OC and CF groups but not in the BC group. Together, our findings suggest opposing effects of WBC miR-155-5p, according to the cell and cancer type. In addition, the results point to miR-155-5p as a candidate biomarker of cancer risk among CF-BRCA1-methylation carriers.
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Affiliation(s)
- Nisreen Al-Moghrabi
- Cancer Epigenetics Section, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
| | - Maram Al-Showimi
- Cancer Epigenetics Section, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
| | - Nujoud Al-Yousef
- Cancer Epigenetics Section, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
| | - Lamya AlOtai
- Department of Life Sciences, College of Science & General Studies, Al Faisal University, Riyadh 11533, Saudi Arabia
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Wu Y, Hong Q, Lu F, Zhang Z, Li J, Nie Z, He B. The Diagnostic and Prognostic Value of miR-155 in Cancers: An Updated Meta-analysis. Mol Diagn Ther 2023; 27:283-301. [PMID: 36939982 DOI: 10.1007/s40291-023-00641-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2023] [Indexed: 03/21/2023]
Abstract
BACKGROUND MicroRNA-155 has been discussed as a biomarker in cancer diagnosis and prognosis. Although relevant studies have been published, the role of microRNA-155 remains uncertain because of insufficient data. METHODS We conducted a literature search in PubMed, Embase, and Web of Science databases to obtain relevant articles and extract data to evaluate the role of microRNA-155 in cancer diagnosis and prognosis. RESULTS The pooled results showed that microRNA-155 presented a remarkable diagnostic value in cancers (area under the curve = 0.90, 95% confidence interval (CI 0.87-0.92; sensitivity = 0.83, 95% CI 0.79-0.87; specificity = 0.83, 95% CI 0.80-0.86), which was maintained in the subgroups stratified by ethnicity (Asian and Caucasian), cancer types (breast cancer, lung cancer, hepatocellular carcinoma, leukemia, and pancreatic ductal adenocarcinoma), sample types (plasma, serum, tissue), and sample size (n >100 and n <100). In prognosis, a combined hazard ratio (HR) showed that microRNA-155 was significantly associated with poor overall survival (HR = 1.38, 95% CI 1.25-1.54) and recurrence-free survival (HR = 2.13, 95% CI 1.65-2.76), and was boundary significant with poor progression-free survival (HR = 1.20, 95% CI 1.00-1.44), but not significant with disease-free survival (HR = 1.14, 95% CI 0.70-1.85). Subgroup analyses in overall survival showed that microRNA-155 was associated with poor overall survival in the subgroups stratified by ethnicity and sample size. However, the significant association was maintained in cancer types subgroups of leukemia, lung cancer, and oral squamous cell carcinoma, but not in colorectal cancer, hepatocellular carcinoma, and breast cancer, and was maintained in sample types subgroups of bone marrow and tissue, but not in plasma and serum. CONCLUSIONS Results from this meta-analysis demonstrated that microRNA-155 was a valuable biomarker in cancer diagnosis and prognosis.
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Affiliation(s)
- Yanan Wu
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, Jiangsu, China
| | - Qiwei Hong
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, Jiangsu, China
| | - Fang Lu
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, Jiangsu, China
| | - Zhongqiu Zhang
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingjing Li
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, Jiangsu, China
| | - Zhenlin Nie
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, Jiangsu, China.
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Qinhuai District, Nanjing, Jiangsu, China.
- Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
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10
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Nehme Z, Roehlen N, Dhawan P, Baumert TF. Tight Junction Protein Signaling and Cancer Biology. Cells 2023; 12:243. [PMID: 36672179 PMCID: PMC9857217 DOI: 10.3390/cells12020243] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 12/29/2022] [Accepted: 01/02/2023] [Indexed: 01/11/2023] Open
Abstract
Tight junctions (TJs) are intercellular protein complexes that preserve tissue homeostasis and integrity through the control of paracellular permeability and cell polarity. Recent findings have revealed the functional role of TJ proteins outside TJs and beyond their classical cellular functions as selective gatekeepers. This is illustrated by the dysregulation in TJ protein expression levels in response to external and intracellular stimuli, notably during tumorigenesis. A large body of knowledge has uncovered the well-established functional role of TJ proteins in cancer pathogenesis. Mechanistically, TJ proteins act as bidirectional signaling hubs that connect the extracellular compartment to the intracellular compartment. By modulating key signaling pathways, TJ proteins are crucial players in the regulation of cell proliferation, migration, and differentiation, all of which being essential cancer hallmarks crucial for tumor growth and metastasis. TJ proteins also promote the acquisition of stem cell phenotypes in cancer cells. These findings highlight their contribution to carcinogenesis and therapeutic resistance. Moreover, recent preclinical and clinical studies have used TJ proteins as therapeutic targets or prognostic markers. This review summarizes the functional role of TJ proteins in cancer biology and their impact for novel strategies to prevent and treat cancer.
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Affiliation(s)
- Zeina Nehme
- Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, 67000 Strasbourg, France
| | - Natascha Roehlen
- Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, 67000 Strasbourg, France
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79098 Freiburg, Germany
| | - Punita Dhawan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, 68198 NE, USA
- Buffet Cancer Center, University of Nebraska Medical Center, Omaha, 68105 NE, USA
- VA Nebraska-Western Iowa Health Care System, Omaha, 68105-1850 NE, USA
| | - Thomas F. Baumert
- Université de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, 67000 Strasbourg, France
- Institut Hospitalo-Universitaire (IHU), Pôle Hépato-Digestif, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France
- Institut Universitaire de France, 75006 Paris, France
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11
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Yadav R, Kumar Y, Dahiya D, Bhatia A. Claudins: The Newly Emerging Targets in Breast Cancer. Clin Breast Cancer 2022; 22:737-752. [PMID: 36175290 DOI: 10.1016/j.clbc.2022.09.001] [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: 08/13/2022] [Accepted: 09/04/2022] [Indexed: 01/25/2023]
Abstract
Claudin-low breast cancers are recently described entities showing low expression of certain claudins and cell adhesion molecules. Claudins constitute the backbone of tight junctions (TJs) formed between 2 cells. Their dysregulation plays a vital role in tumorigenesis. First part of the article focuses on the role of claudins in the TJ organization, their structural-functional characteristics, and post-transcriptional and translational modifications. The latter part of the review attempts to summarize existing knowledge regarding the status of claudins in breast cancer. The article also provides an overview of the effect of claudins on tumor progression, metastasis, stemness, chemotherapy resistance, and their crosstalk with relevant signaling pathways in breast cancer. Claudins can act as 2-edged swords in tumors. Some claudins have either tumor-suppressive/ promoting action, while others work as both in a context-dependent manner. Claudins regulate many important events in breast cancer. However, the intricacies involved in their activity are poorly understood. Post-translational modifications in claudins and their impact on TJ integrity, function, and tumor behavior are still unclear. Although their role in adverse events in breast cancer is recognized, their potential to serve as relevant targets for future therapeutics, especially for difficult-to-treat subtypes of the above malignancy, remains to be explored.
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Affiliation(s)
- Reena Yadav
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yashwant Kumar
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Divya Dahiya
- Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Alka Bhatia
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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12
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Beg A, Parveen R, Fouad H, Yahia ME, Hassanein AS. Role of different non-coding RNAs as ovarian cancer biomarkers. J Ovarian Res 2022; 15:72. [PMID: 35715825 PMCID: PMC9206245 DOI: 10.1186/s13048-022-01002-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/18/2022] [Indexed: 11/10/2022] Open
Abstract
Background Among many gynecological malignancies ovarian cancer is the most prominent and leading cause of female mortality worldwide. Despite extensive research, the underlying cause of disease progression and pathology is still unknown. In the progression of ovarian cancer different non-coding RNAs have been recognized as important regulators. The biology of ovarian cancer which includes cancer initiation, progression, and dissemination is found to be regulated by different ncRNA. Clinically ncRNA shows high prognostic and diagnostic importance. Results In this review, we prioritize the role of different non-coding RNA and their perspective in diagnosis as potential biomarkers in the case of ovarian cancer. Summary of some of the few miRNAs involved in epithelial ovarian cancer their expression and clinical features are being provided in the table. Also, in cancer cell proliferation, apoptosis, invasion, and migration abnormal expression of piRNAs are emerging as a crucial regulator hence the role of few piRNAs is being given. Both tRFs and tiRNAs play important roles in tumorigenesis and are promising diagnostic biomarkers and therapeutic targets for cancer. lncRNA has shown a leading role in malignant transformation and potential therapeutic value in ovarian cancer therapy. Conclusions Hence in this review we demonstrated the role of different ncRNA that play an important role in serving strong potential as a therapeutic approach for the treatment of ovarian cancer.
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Affiliation(s)
- Anam Beg
- Department of Computer Science, Jamia Millia Islamia, New Delhi, 110025, India
| | - Rafat Parveen
- Department of Computer Science, Jamia Millia Islamia, New Delhi, 110025, India.
| | - Hassan Fouad
- Applied Medical Science Department, CC, King Saud University, P.O Box 10219, Riyadh, 11433, Saudi Arabia
| | - M E Yahia
- Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Azza S Hassanein
- Biomedical Engineering Department, Faculty of Engineering, Helwan University, Cairo, Egypt
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13
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Ke F, Ren C, Zhai Z, Gao X, Wei J, Zhu Y, Zhi Y. LINC01234 regulates microRNA-27b-5p to induce the migration, invasion and self-renewal of ovarian cancer stem cells through targeting SIRT5. Cell Cycle 2022; 21:1020-1033. [PMID: 35230909 PMCID: PMC9037434 DOI: 10.1080/15384101.2022.2040282] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
LINC01234 has been suggested to correlate with the survival of ovarian cancer (OS), but its role in the properties of OC stem cells (OCSCs) has been rarely described. We aim to investigate the effect of LINC01234 on the differentiation and self-renewal of OCSCs through adsorption of microRNA (miR)-27b-5p to target sirtuins 5 (SIRT5). Expression of LINC01234 and SIRT5 in OC and normal samples included in TCGA and GTEx was searched through the GEPIA2 database. Bioinformatics analysis was conducted to predict the relation of LINC01234, miR-27b-5p and SIRT5. Expression of LINC01234, miR-27b-5p and SIRT5 in OC tissues and cells was detected. OCSCs were cultured and identified. CD133+ OCSCs were introduced with related oligonucleotides or vectors of LINC01234 or miR-27b-5p and SIRT5 to figure out their roles in OCSCs progression and tumorigenesis in vivo. The interaction of miR-27b-5p with LINC01234 or SIRT5 was analyzed. Bioinformatics analysis suggested that LINC01234 was very likely to influence SIRT5 and regulate the development of OC through miR-27b-5p. Up-regulated LINC01234 exhibited in OC tissues and cells. Down-regulated LINC01234 or elevated miR-27b-5p suppressed OCSCs progression and tumorigenesis in vivo. LINC01234 could restore SIRT5 expression by binding to miR-27b-5p. Down-regulated miR-27b-5p reversed the effect of silenced LINC01234 on OCSCs development and tumorigenesis in vivo. Up-regulation of SIRT5 reduced the effects of elevated miR-27b-5p on OCSCs progression and tumorigenesis in vivo. LINC01234 regulates miR-27b-5p to induce the migration, invasion and self-renewal of OCSCs through targeting SIRT5.
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Affiliation(s)
- Fang Ke
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Chenchen Ren
- Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China,CONTACT Chenchen Ren Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7 Kangfuqian Street, Erqi District, Zhengzhou, Henan, 450052, China
| | - Zihan Zhai
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Henan, China
| | - Xiang Gao
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jing Wei
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yuanhang Zhu
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yunxiao Zhi
- Department of Gynaecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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14
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Szczepanek J, Skorupa M, Tretyn A. MicroRNA as a Potential Therapeutic Molecule in Cancer. Cells 2022; 11:1008. [PMID: 35326459 PMCID: PMC8947269 DOI: 10.3390/cells11061008] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/11/2022] [Accepted: 03/16/2022] [Indexed: 12/11/2022] Open
Abstract
Small noncoding RNAs, as post-translational regulators of many target genes, are not only markers of neoplastic disease initiation and progression, but also markers of response to anticancer therapy. Hundreds of miRNAs have been identified as biomarkers of drug resistance, and many have demonstrated the potential to sensitize cancer cells to therapy. Their properties of modulating the response of cells to therapy have made them a promising target for overcoming drug resistance. Several methods have been developed for the delivery of miRNAs to cancer cells, including introducing synthetic miRNA mimics, DNA plasmids containing miRNAs, and small molecules that epigenetically alter endogenous miRNA expression. The results of studies in animal models and preclinical studies for solid cancers and hematological malignancies have confirmed the effectiveness of treatment protocols using microRNA. Nevertheless, the use of miRNAs in anticancer therapy is not without limitations, including the development of a stable nanoconstruct, delivery method choices, and biodistribution. The aim of this review was to summarize the role of miRNAs in cancer treatment and to present new therapeutic concepts for these molecules. Supporting anticancer therapy with microRNA molecules has been verified in numerous clinical trials, which shows great potential in the treatment of cancer.
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Affiliation(s)
- Joanna Szczepanek
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Ul. Wilenska 4, 87-100 Torun, Poland;
| | - Monika Skorupa
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Ul. Wilenska 4, 87-100 Torun, Poland;
- Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Ul. Lwowska 1, 87-100 Torun, Poland;
| | - Andrzej Tretyn
- Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Ul. Lwowska 1, 87-100 Torun, Poland;
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15
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Sahabi K, Selvarajah GT, Mokrish A, Rasedee A, Kqueen CY. Development and molecular characterization of doxorubicin-resistant canine mammary gland tumour cells. JOURNAL OF APPLIED ANIMAL RESEARCH 2022. [DOI: 10.1080/09712119.2022.2032719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Kabiru Sahabi
- Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia
| | - Gayathri T. Selvarajah
- Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia
- UPM-MAKNA Cancer Research Laboratory (CANRES), Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia
| | - Ajat Mokrish
- Department of Veterinary Preclinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia
| | - Abdullah Rasedee
- Department of Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia
| | - Cheah Y. Kqueen
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
- UPM-MAKNA Cancer Research Laboratory (CANRES), Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia
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16
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Zhang X, Zhu W, Lu J. microRNA-133b Regulates Cell Proliferation and Cell Cycle Progression via Targeting HuR in Colorectal Cancer. J BIOMATER TISS ENG 2022. [DOI: 10.1166/jbt.2022.2910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
MicroRNAs (miRNAs/miRs) have been identified to serve a key role in the development of tumors. However, the role of miR-133b in colorectal cancer (CRC) remains largely unclear. This study will investigate the role and mechanism of miR-133b in CRC. Reverse transcription-quantitative
polymerase chain reaction analysis was performed to detect the level of miR-133b in CRC cell lines. Bioinformatics software TargetScan predicted the potential target genes of miR-133b, and a dual luciferase reporter assay was used to confirm this. To investigate the role of miR-133b in CRC
cells, miR-133b was upregulated or downregulated in CRC cell lines (SW620 and HT-29) by transfecting with a miR-133b mimic or inhibitor, respectively. Subsequently, cell viability was analyzed using MTT assay, whereas cell apoptosis and the cell cycle distribution were analyzed by flow cytometry.
In addition, the associated protein levels were detected using western blot analysis. The results demonstrated that miR-133b was significantly downregulated in CRC cell lines when compared with the normal colonic epithelial NCM-460 cell line. Human antigen R (HuR; also termed ELAVL1) was demonstrated
to be a direct target of miR-133b and was negatively regulated by miR-133b. HuR was also notably upregulated in the CRC cell lines when compared with the normal control. Transfection of SW620 and HT-29 cells with the miR-133b mimic significantly inhibited cell viability, and induced cell apoptosis
and G1 phase arrest, while upregulation of HuR demonstrated the opposite effects. Furthermore, the present data demonstrated that the miR-133b mimic significantly enhanced the protein levels of p21 and p27, and downregulated cyclin D1 and cyclin A levels in SW620 and HT-29 cells;
the opposite effects were observed following treatment with the miR-133b inhibitor. In conclusion, the data indicate that miR-133b suppressed CRC cell growth by targeting HuR.
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Affiliation(s)
- Xiaoyan Zhang
- Department of General Surgery, The Second People’s Hospital of Nantong, Nantong, Jiangsu 226001, P. R. China
| | - Wei Zhu
- Department of Gynaecology and Obstetrics, The Second People’s Hospital of Nantong, Nantong, Jiangsu 226001, P. R. China
| | - Junjie Lu
- Department of General Surgery, The Second People’s Hospital of Nantong, Nantong, Jiangsu 226001, P. R. China
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17
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Role of microRNAs in the Pathophysiology of Ulcerative Colitis. IMMUNO 2021. [DOI: 10.3390/immuno1040039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Ulcerative colitis (UC) is an intractable disorder characterized by a chronic inflammation of the colon. Studies have identified UC as a multifactorial disorder affected by both genetic and environmental factors; however, the precise mechanism remains unclear. Recent advances in the field of microRNA (miRNA) research have identified an association between this small non-coding RNA in the pathophysiology of UC and altered miRNA expression profiles in patients with UC. Nevertheless, the roles of individual miRNAs are uncertain due to heterogeneity in both research samples and clinical backgrounds. In this review, we focus on miRNA expression in colonic mucosa where inflammation occurs in UC and discuss the potential roles of individual miRNAs in disease development, outlining the pathophysiology of UC.
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18
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Svoronos AA, Campbell SG, Engelman DM. MicroRNA function can be reversed by altering target gene expression levels. iScience 2021; 24:103208. [PMID: 34755085 PMCID: PMC8560630 DOI: 10.1016/j.isci.2021.103208] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 07/14/2021] [Accepted: 09/29/2021] [Indexed: 11/17/2022] Open
Abstract
Paradoxically, many microRNAs appear to exhibit entirely opposite functions when placed in different contexts. For example, miR-125b has been shown to be pro-apoptotic in some studies, but anti-apoptotic in others. To investigate this phenomenon, we combine computational modeling with experimental approaches to examine how the function of miR-125b in apoptosis varies with respect to the expression levels of its pro-apoptotic and anti-apoptotic targets. In doing so, we elucidate a general trend that miR-125b is more pro-apoptotic when its anti-apoptotic targets are overexpressed, whereas it is more anti-apoptotic when its pro-apoptotic targets are overexpressed. We show that it is possible to completely reverse miR-125b′s function in apoptosis by modifying the expression levels of its target genes. Furthermore, miR-125b′s function may also be altered by the presence of anticancer drugs. These results suggest that the function of a microRNA can vary substantially and is dependent on its target gene expression levels.
Many miRNAs exhibit entirely opposite functions when placed in different contexts miR-125b can be pro- or anti-apoptotic depending on target gene expression levels The function of a miRNA can be reversed by altering target gene expression levels The presence of anticancer drugs can also alter a miRNA's function
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Affiliation(s)
- Alexander A Svoronos
- Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.,Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Av., P.O. Box 208114, New Haven, CT 06520, USA
| | - Stuart G Campbell
- Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
| | - Donald M Engelman
- Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Av., P.O. Box 208114, New Haven, CT 06520, USA
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19
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Wang L, Ren C, Xu Y, Yang L, Chen Y, Zhu Y. The LINC00922 aggravates ovarian cancer progression via sponging miR-361-3p. J Ovarian Res 2021; 14:77. [PMID: 34116704 PMCID: PMC8194245 DOI: 10.1186/s13048-021-00828-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/20/2021] [Indexed: 02/07/2023] Open
Abstract
Background Long noncoding RNA (lncRNA) LINC00922 has been reported to promote tumorigenesis of lung and breast cancer. However, the functions and mechanisms of LINC00922 in ovarian cancer (OC) remain unclarified. The current study aims to clarify the detailed functions and underlying mechanisms of LINC00922 in the progression of OC. Methods LINC00922 expression in OC tissues and cells was identified by a comprehensive strategy of data miming, computational biology and quantitative real-time polymerase chain reaction (RT-qPCR) experiment. In vitro CCK-8, wound healing, transwell invasion, western blotting and in vivo tumorigenesis assays LINC00922 were conducted to evaluate the functions of LINC00992. Subsequently, bioinformatics technology and dual luciferase reporter assay were performed to confirm the between miR-361-3p and LINC00922 or CLDN1. Finally, rescue experiments were performed to confirm whether LINC00922 effect functions of OC cells through regulation of miR-361-3p. Results LINC00922 was significantly upregulated in OC tissues and cell lines, which is significantly positively corelated with the poor prognosis of patients with OC. LINC00922 knockdown inhibited proliferation and tumorigenesis of OC cells in vitro and vivo. In addition, LINC00922 knockdown suppressed migration, invasion, and EMT of OC cells in vitro. Mechanically, LINC00922 could competitively bind with miR-361-3p to relieve the repressive effect of miR-361-3p on its target gene CLDN1 in OC cells. In addition, silencing miR-361-3p promoted OC cell proliferation, migration, invasion, EMT and Wnt/β-catenin signaling, while LINC00922 knockdown inhibited Wnt/β-catenin signaling by upregulating miR-361-3p. Rescue experiments revealed that LINC00922 knockdown inhibited OC cell proliferation, migration, invasion and EMT by regulating miR-361-3p. Conclusion This study suggested that LINC00922 could competitively bind with miR-361-3p to promote the CLDN1 expression and activate Wnt/β-catenin signaling in OC progression, which providing a promising therapeutically target for OC. Supplementary Information The online version contains supplementary material available at 10.1186/s13048-021-00828-7.
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Affiliation(s)
- Liping Wang
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, 450052, China
| | - Chenchen Ren
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, 450052, China.
| | - Yajuan Xu
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, 450052, China
| | - Li Yang
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, 450052, China
| | - Yannan Chen
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, 450052, China
| | - Yuanhang Zhu
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, 450052, China
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20
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Mortazavi SS, Bahmanpour Z, Daneshmandpour Y, Roudbari F, Sheervalilou R, Kazeminasab S, Emamalizadeh B. An updated overview and classification of bioinformatics tools for MicroRNA analysis, which one to choose? Comput Biol Med 2021; 134:104544. [PMID: 34119921 DOI: 10.1016/j.compbiomed.2021.104544] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 05/30/2021] [Accepted: 05/30/2021] [Indexed: 12/16/2022]
Abstract
The term 'MicroRNA' (miRNA) refers to a class of small endogenous non-coding RNAs (ncRNAs) regenerated from hairpin transcripts. Recent studies reveal miRNAs' regulatory involvement in essential biological processes through translational repression or mRNA degradation. Recently, there is a growing body of literature focusing on the importance of miRNAs and their functions. In this respect, several databases have been developed to manage the dispersed data produced. Therefore, it is necessary to know the parameters and characteristics of each database to benefit their data. Besides, selecting the correct database is of great importance to scientists who do not have enough experience in this field. A comprehensive classification along with an explanation of the information contained in each database leads to facilitating access to these resources. In this regard, we have classified relevant databases into several categories, including miRNA sequencing and annotation, validated/predicted miRNA targets, disease-related miRNA, SNP in miRNA sequence or target site, miRNA-related pathways, or gene ontology, and mRNA-miRNA interactions. Hence, this review introduces available miRNA databases and presents a convenient overview to inform researchers of different backgrounds to find suitable miRNA-related bioinformatics web tools and relevant information rapidly.
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Affiliation(s)
| | - Zahra Bahmanpour
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yousef Daneshmandpour
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | | | - Somayeh Kazeminasab
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Research Vice-Chancellor, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Babak Emamalizadeh
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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21
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Potential functions of hsa-miR-155-5p and core genes in chronic myeloid leukemia and emerging role in human cancer: A joint bioinformatics analysis. Genomics 2021; 113:1647-1658. [PMID: 33862181 DOI: 10.1016/j.ygeno.2021.04.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 02/07/2021] [Accepted: 04/05/2021] [Indexed: 12/13/2022]
Abstract
Considering the critical roles of hsa-miR-155-5p participated in hematopoietic system, this study aims to clarify the possible pathogenesis of chronic myeloid leukemia (CML) induced by hsa-miR-155-5p.Three different strategies were employed, namely a network-based pipeline, a survival analysis and genetic screening method, and a simulation modeling approach, to assess the oncogenic role of hsa-miR-155-5p in CML. We identified new potential roles of hsa-miR-155-5p in CML, involving the BCR/ABL-mediated leukemogenesis through MAPK signaling. Several promising targets including E2F2, KRAS and FLI1 were screened as candidate diagnostic marker genes. The survival analysis revealed that mRNA expression of E2F2, KRAS and FLI1 was negatively correlated with hsa-miR-155-5p and these targets were significantly associated with poor overall survival. Furthermore, an overlap between CML-related genes and hsa-miR-155-5p target genes was revealed using competing endogenous RNA (ceRNA) networks analysis. Taken together, our results reveal the dynamic regulatory aspect of hsa-miR-155-5p as potential player in CML pathogenesis.
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22
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Withaferin A mitigates metastatic traits in human oral squamous cell carcinoma caused by aberrant claudin-1 expression. Cell Biol Toxicol 2021; 38:147-165. [PMID: 33665778 DOI: 10.1007/s10565-021-09584-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 01/24/2021] [Indexed: 12/27/2022]
Abstract
Abnormal expression of claudin-1 (CLDN1) has important roles in carcinogenesis and metastasis in various cancers. The role of CLDN1 in human oral squamous cell carcinoma (OSCC) remains unknown. Here, we report the functional role of CLDN1 in metastasis of human OSCC, as a potential target regulated by withaferin A. From gene expression profiling with microarray technology, we found that the majority of notable differentially expressed genes were classified into migration/invasion category. Withaferin A impaired the motility of human OSCC cells in vitro and suppressed metastatic nodule formation in an in vivo metastasis model, both associated with reduced CLDN1. CLDN1 overexpression enhanced metastatic nodule formation in vivo, resulting in severe metastatic lesions in lung tissue. Moreover, CLDN1 expression was positively correlated to lymphatic metastasis in OSCC patients. The impaired motility of human OSCC cells upon withaferin A treatment was restored by CLDN1 overexpression. Furthermore, upregulation of let-7a induced by withaferin A was inversely correlated to CLDN1 expression. Overall, these give us an insight into the function of CLDN1 for prognosis and treatment of human OSCC, substantiating further investigation into the use of withaferin A as good anti-metastatic drug candidate.
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23
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Shan C, Chen X, Cai H, Hao X, Li J, Zhang Y, Gao J, Zhou Z, Li X, Liu C, Li P, Wang K. The Emerging Roles of Autophagy-Related MicroRNAs in Cancer. Int J Biol Sci 2021; 17:134-150. [PMID: 33390839 PMCID: PMC7757044 DOI: 10.7150/ijbs.50773] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 10/29/2020] [Indexed: 12/11/2022] Open
Abstract
Autophagy is a conserved catabolic process involving the degradation and recycling of damaged biomacromolecules or organelles through lysosomal-dependent pathways and plays a crucial role in maintaining cell homeostasis. Consequently, abnormal autophagy is associated with multiple diseases, such as infectious diseases, neurodegenerative diseases and cancer. Currently, autophagy is considered to be a dual regulator in cancer, functioning as a suppressor in the early stage while supporting the growth and metastasis of cancer cells in the later stage and may also produce therapeutic resistance. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level by silencing targeted mRNA. MiRNAs have great regulatory potential for several fundamental biological processes, including autophagy. In recent years, an increasing number of studies have linked miRNA dysfunction to the growth, metabolism, migration, metastasis, and responses of cancer cells to therapy. Therefore, the study of autophagy-related miRNAs in cancer will provide insights into cancer biology and lead to the development of novel anti-cancer strategies. In the present review, we summarise the current knowledge of miRNA dysregulation during autophagy in cancer, focusing on the relationship between autophagy and miRNAs, and discuss their involvement in cancer biology and cancer treatment.
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Affiliation(s)
- Chan Shan
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Xinzhe Chen
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Hongjing Cai
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Xiaodan Hao
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Jing Li
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yinfeng Zhang
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Jinning Gao
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Zhixia Zhou
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Xinmin Li
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Cuiyun Liu
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Peifeng Li
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Kun Wang
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
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Mollasalehi H, Shajari E. A colorimetric nano-biosensor for simultaneous detection of prevalent cancers using unamplified cell-free ribonucleic acid biomarkers. Bioorg Chem 2020; 107:104605. [PMID: 33421955 DOI: 10.1016/j.bioorg.2020.104605] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 12/12/2020] [Accepted: 12/25/2020] [Indexed: 12/29/2022]
Abstract
Early detection of cancer increases the chance of effective treatment and survival rates. The aim of this study is to develop a rapid and non-invasive nano-biosensing method to screen common lethal cancers in their early stages. In that regard, two circulating microRNA (miR-21, miR-155) biomarkers, which are upregulated in plasma in prevalent cancers, were targeted by a rapid and colorimetric nano-biosensor based on non-crosslinking Au-nanoprobes without amplification requirement. Multiple cancerous cell lines, including A549, MCF7, HT-29, A2780, AGS, MKN-45, and SW-1736 and the primary fibroblast were examined with naked eyes after the hybridization assay using exogenous biomarkers. The results were also confirmed by spectroscopy analysis. The upregulated miRNAs in cancerous cell lines caused a significant blue shift in the Au-nanoprobe absorbance spectrum while the samples isolated from normal cells remained intact red. The limit of detection (LOD) of the method was determined to be less than one ng/µL of total isolated miRNA using an instrument-free visual method. The developed geno-sensing method could serve as a simple, point-of-care platform for cancer prognosis and diagnosis, leading to operative nano-theranostics.
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Affiliation(s)
- Hamidreza Mollasalehi
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Velenjak, Tehran Postal Code: 1983969411, Iran.
| | - Elmira Shajari
- Protein Research Center (PRC), Shahid Beheshti University, Velenjak, Tehran, Iran
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25
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Zheng Q, Dai X, Fang W, Zheng Y, Zhang J, Liu Y, Gu D. Overexpression of microRNA-367 inhibits angiogenesis in ovarian cancer by downregulating the expression of LPA1. Cancer Cell Int 2020; 20:476. [PMID: 33024414 PMCID: PMC7531134 DOI: 10.1186/s12935-020-01551-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023] Open
Abstract
Background Compelling evidences reported the role of microRNAs (miRNAs) in ovarian cancer. However, little was known regarding the molecular mechanism of miR-367 in ovarian cancer. This study intended to investigate the role and regulatory mechanism of miR-367 in ovarian cancer involving lysophosphatidic acid receptor-1 (LPA1). Methods Potentially regulatory miRNAs in ovarian cancer were obtained from bioinformatics analysis. RT-qPCR was used to detect miR-367 expression in both ovarian cancer tissues and relevant adjacent normal tissues. Relationship between miR-367 and LPA1 was predicted by miRNA database and further verified using dual luciferase reporter gene assay and RIP. EdU and Transwell assay were used to measure the proliferation and invasion ability of cells. Moreover, tube formation and chick chorioallantois membrane (CAM) assay were performed to determine angiogenesis of human umbilical vein endothelial cells (HUVECs). Finally, the roles of LPA1 in tumor growth was also studied using nude mice xenograft assay. Results High expression of LPA1 and low expression of miR-367 were observed in ovarian cancer tissues and cells. Overexpressed miR-367 downregulated LPA1 expression to inhibit proliferation, invasion, and angiogenesis of cancer cells. Low expression of LPA1 suppressed tumor formation and repressed angiogenesis in ovarian in vivo. Conclusion All in all, overexpression of miR-367 downregulated LPA1 expression to inhibit ovarian cancer progression, which provided a target for the cancer treatment.
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Affiliation(s)
- Qingling Zheng
- Department of Obstetrics and Gynecology, School of Medicine and Nursing Sciences, Huzhou University, Huzhou Central Hospital, Huzhou, 313000 People's Republic of China
| | - Xin Dai
- Department of Pathology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153 Jiangsu People's Republic of China
| | - Wei Fang
- Department of Pathology, Huzhou Central Hospital, Huzhou, 313000 People's Republic of China
| | - Yan Zheng
- Department of Pathology, Huzhou Central Hospital, Huzhou, 313000 People's Republic of China
| | - Jin Zhang
- Department of Pathology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153 Jiangsu People's Republic of China
| | - Yanxiang Liu
- Department of Pathology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153 Jiangsu People's Republic of China
| | - Donghua Gu
- Department of Pathology, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153 Jiangsu People's Republic of China
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26
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Singh A, Srivastava N, Yadav A, Ateeq B. Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma. Neoplasia 2020; 22:497-510. [PMID: 32896760 PMCID: PMC7481885 DOI: 10.1016/j.neo.2020.08.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 08/01/2020] [Accepted: 08/05/2020] [Indexed: 01/05/2023]
Abstract
Glioblastoma (GBM) represents the most aggressive malignancy of the central nervous system. Increased expression of Angiotensin II Receptor Type 1 (AGTR1) has been associated with proliferative and infiltrative properties of glioma cells. However, the underlying mechanism of AGTR1 upregulation in GBM is still unexplored. To understand the post-transcriptional regulation of AGTR1 in GBM, we screened 3'untranslated region (3'UTR) of AGTR1 for putative miRNA binding by using prediction algorithms. Interestingly, miR-155 showed conserved binding on the 3'UTR of AGTR1, subsequently confirmed by luciferase reporter assay. Furthermore, miR-155 overexpressing GBM cells show decrease in AGTR1 expression accompanied with reduced cell proliferation, invasion, foci formation and anchorage-independent growth. Strikingly, immunodeficient mice implanted with stable miR-155 overexpressing SNB19 cells show negligible tumor growth. Notably, miR-155 attenuates NF-κB signaling downstream of AGTR1 leading to reduced CXCR4 as well as AGTR1 levels. Mechanistically, miR-155 mitigates AGTR1-mediated angiogenesis, epithelial-to-mesenchymal transition, stemness, and MAPK signaling. Similar effects were observed by using pharmacological inhibitor of IκB Kinase (IKK) complex in multiple cell-based assays. Taken together, we established that miRNA-155 post-transcriptionally regulates AGTR1 expression, abrogates AGTR1/NF-κB/CXCR4 signaling axis and elicits pleiotropic anticancer effects in GBM. This study opens new avenues for using IKK inhibitors and miRNA-155 replacement therapies for the treatment of AGTR1-positive malignancies.
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MESH Headings
- Animals
- Apoptosis
- Brain Neoplasms/genetics
- Brain Neoplasms/metabolism
- Brain Neoplasms/pathology
- Cell Movement
- Cell Proliferation
- Female
- Gene Expression Regulation, Neoplastic
- Glioblastoma/genetics
- Glioblastoma/metabolism
- Glioblastoma/pathology
- Humans
- Mice
- Mice, Inbred NOD
- Mice, SCID
- MicroRNAs/genetics
- NF-kappa B/genetics
- NF-kappa B/metabolism
- Receptor, Angiotensin, Type 1/genetics
- Receptor, Angiotensin, Type 1/metabolism
- Receptors, CXCR4/genetics
- Receptors, CXCR4/metabolism
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
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Affiliation(s)
- Anukriti Singh
- Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India; Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India
| | - Nidhi Srivastava
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali 304022, Rajasthan, India
| | - Anjali Yadav
- Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India
| | - Bushra Ateeq
- Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India.
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27
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Ysrafil Y, Astuti I, Anwar SL, Martien R, Sumadi FAN, Wardhana T, Haryana SM. MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression. Adv Pharm Bull 2020; 10:630-637. [PMID: 33062603 PMCID: PMC7539305 DOI: 10.34172/apb.2020.076] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 01/28/2020] [Accepted: 02/03/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose: Ovarian cancer is the most lethal of gynecological malignancies. Recently, the development of microRNA (miRNA) -based therapeutics that could impact broad cellular programs, leading to inhibition of cancer cell viability, is gaining attention in the therapeutic landscape. The therapy is based on the presence of aberrant expressions of miRNA in cancer cells. Decreasing of tumor suppressor miRNA expression causes upregulation of oncoprotein, which worsens the prognosis of the ovarian cancer. Methods: miR-155-5p mimics were carried by chitosan nanoparticles using new nanotechnology methods. Cellular uptake of miRNA was assessed by fluorescence microscope while MTT and qPCR assay were used to determine miRNA profile and the effect of CS-NP/miRNA on SKOV3 cells. Results: Results of profiling validated using quantitative realtime-polymerase chain reaction (PCR) found one of the most altered tumor suppressor miRNAs, miR-155-5p was downregulated 892.15-fold. According to bioinformatic analysis we identified the miRNA could recognize and regulate HIF1α expression. Transfection of mimics for miR-155-5p showed significantly increased miR-155-5p endogen SKOV3 expression level compared to the control group. We found differences after transfection mimics for miR-155-5p 31.5 and 63 nanoMolar. Increasing of miR-155-5p endogen lead to diminished SKOV3 viability (by 30%; <0.05 at concentration 80 nanoMolar). These mimics may cause an increase in upregulated miR-155-5p endogen that can reduce HIF1α expression. Here we found 2-fold and 2.8-fold reduction of HIF1α expression level after transfection compared to the control group. Conclusion: According to these findings, the mimics miR-155-5p can inhibit ovarian cancer cell proliferation by regulating HIF1α expression.
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Affiliation(s)
- Ysrafil Ysrafil
- Departement of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia
| | - Indwiani Astuti
- Departement of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia
| | - Sumadi Lukman Anwar
- Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia
| | - Ronny Martien
- Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Sekip Utara Yogyakarta 55281, Indonesia
| | | | - Tirta Wardhana
- Faculty of Medicine, Jenderal Soedirman University, Dr. Gumbreg, Mersi, Banyumas, Jawa Tengah 53112, Indonesia
| | - Sofia Mubarika Haryana
- Medicine and Health Sciences of Doctoral Program, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia
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Gajda E, Godlewska M, Mariak Z, Nazaruk E, Gawel D. Combinatory Treatment with miR-7-5p and Drug-Loaded Cubosomes Effectively Impairs Cancer Cells. Int J Mol Sci 2020; 21:E5039. [PMID: 32708846 PMCID: PMC7404280 DOI: 10.3390/ijms21145039] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/14/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Multidrug resistance (MDR) is an emerging problem in the treatment of cancer. Therefore, there is a necessity for novel strategies that would sensitize tumor cells to the administered chemotherapeutics. One of the innovative approaches in fighting drug-resistant tumors is the treatment of cancer with microRNA (miRNA), or the use of cubosomes (lipid nanoparticles) loaded with drugs. Here, we present a study on a novel approach, which combines both tools. METHODS Cubosomes loaded with miR-7-5p and chemotherapeutics were developed. The effects of drug- and miRNA-loaded vehicles on glioma- (A172, T98G), papillary thyroid- (TPC-1) and cervical carcinoma-derived (HeLa) cells were analyzed using molecular biology techniques, including quantitative real-time PCR, MTS-based cell proliferation test, flow cytometry and spheroids formation assay. RESULTS The obtained data indicate that miR-7-5p increases the sensitivity of the tested cells to the drug, and that nanoparticles loaded with both miRNA and the drug produce a greater anti-tumor effect in comparison to the free drug treatment. It was found that an increased level of apoptosis in the drug/miRNA co-treated cells is accompanied by an alternation in the expression of the genes encoding for key MDR proteins of the ABC family. CONCLUSIONS Overall, co-administration of miR-7-5p with a chemotherapeutic can be considered a promising strategy, leading to reduced MDR and the induction of apoptosis in cancer cells.
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Affiliation(s)
- Ewa Gajda
- Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland;
| | - Marlena Godlewska
- Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland;
| | - Zenon Mariak
- Department of Neurosurgery, Medical University of Bialystok, M. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland;
| | - Ewa Nazaruk
- Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland;
| | - Damian Gawel
- Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland;
- Department of Immunohematology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland
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29
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Jing C, Yan L, Wei Z, Shoumin Z, Guangwen Y, Jiangan Z, Xuesong J, Hongxiang C, Ziyu D, Jianguo L. Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma. Drug Deliv Transl Res 2020; 11:1000-1008. [PMID: 32572699 DOI: 10.1007/s13346-020-00811-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
MicroRNAs (miRNAs) are involved in the pathogenesis of several cancers including skin squamous cell carcinoma (sSCC), and miR-134 is reported to possess tumor inhibition properties. The present study is an attempt to study the mechanistic role and antitumor property of miR-134 in sSCC. For this purpose, α-tocopherol PEG 1000 succinate (TPGS)-based PEGylated liposome was formulated and encapsulated with miR-134 (TP-miR-LP). CCK-8 assay results showed that miR-134 exhibited a concentration-dependent decrease in the cell viability of A-431 cells. Importantly, TPGS-based TP-miR-LP showed significantly (p < 0.05) lower cell viability compared with that of miR-134-loaded PEGylated liposome (miR-LP). Western blot analysis clearly indicates the specific targeting ability of miR-134 (TP-miR-LP) towards the Forkhead Box M1 (FOXM1) in the cancer cells. The apoptosis rate of the cells was significantly increased in TP-miR-LP (~ 38%) than that of miR-LP (~ 15%), respectively with significant inhibition of cell migration. Importantly, tumors treated with TP-miR-LP grew significantly slower compared with that of any other formulation group in the xenograft animal model. Present results clearly demonstrate the tumor suppressive effect of miR-134 through the downregulation of FOXM1 which subsequently blocks the downstream signaling pathways. These findings suggest the translational potential of miR-134 towards designing formulation strategies for sSCC treatment. Graphical abstract.
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Affiliation(s)
- Chen Jing
- Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China
| | - Li Yan
- Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China
| | - Zhang Wei
- Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China
| | - Zhang Shoumin
- Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China
| | - Yin Guangwen
- Dermatology of Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhang Jiangan
- Dermatology of Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jia Xuesong
- Department of Dermatology, The First Affiliated Hospital of The Medical College, Shihezi University, Shihezi, Xinjiang, China
| | - Chen Hongxiang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Duan Ziyu
- Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China
| | - Li Jianguo
- Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, 450003, Henan, China.
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30
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Ben Q, Sun Y, Liu J, Wang W, Zou D, Yuan Y. Nicotine promotes tumor progression and epithelial-mesenchymal transition by regulating the miR-155-5p/NDFIP1 axis in pancreatic ductal adenocarcinoma. Pancreatology 2020; 20:698-708. [PMID: 32354626 DOI: 10.1016/j.pan.2020.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 02/26/2020] [Accepted: 04/05/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND Nicotine, the major component of cigarette smoke, has been reported to promote pancreatic ductal adenocarcinoma (PDAC) growth and invasion. Deregulation of microRNA (miRNA) expression is found in many cancers, including PDAC. The effects of nicotine on miRNAs change in PDAC progression remain unknown. METHODS The effects of cigarette smoking/nicotine exposure on PDAC cell lines and tissues were evaluated. Quantitative real-time PCR and in situ hybridization assays were used to determine miR-155-5p expression in human PDAC tissue and cell lines upon cigarette smoking/nicotine exposure. Bioinformatics, loss-of-function experiments, luciferase reporter assay were performed to validate Nedd4 family interacting protein 1 (NDFIP1) as a direct target of miR-155-5p. The potentials of systemic miR-155-5p inhibitor-based therapy in overcoming nicotine exposure were evaluated in tumor xenograft model. RESULTS Nicotine promoted PDAC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a dose-response manner. MiR-155-5p was found to be highly expressed in PDAC cell lines and tissues upon cigarette smoking/nicotine exposure. Functional studies showed that miR-155-5p knockdown could override the enhancement of oncogenic activity due to nicotine exposure in vitro and in vivo by directly interacting with the 3' untranslated regions (UTRs) of NDFIP1. CONCLUSIONS These data demonstrate that nicotine-regulated miR-155-5p/NDFIP1 promotes tumor progression and EMT of PDAC.
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Affiliation(s)
- Qiwen Ben
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
| | - Yunwei Sun
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
| | - Jun Liu
- Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
| | - Weiyi Wang
- Department of Gastroenterology, Ruijin North Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
| | - Yaozong Yuan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
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Abstract
Introduction: Ovarian carcinoma (OC) is the leading cause of death in women with gynecologic cancers. Most patients are diagnosed at an advanced stage with a low five-year survival rate of 20-30%. Discovering novel biomarkers for early detection and outcome prediction of OC is an urgent medical need. miRNAs, a group of small non-coding RNAs, play critical roles in multiple biologic processes and cancer pathogenesis.Areas covered: We provide an in-depth look at the functions of miRNAs in OC, particularly focusing on their roles in chemoresistance and metastasis in OC. We also discuss the biological and clinical significance of miRNAs in exosomes and expand on long non-coding RNA which acts as ceRNA of miRNAs.Expert opinion: miRNAs participate in many biological processes including proliferation, apoptosis, chemoresistance, metastasis, epithelial-mesenchymal transition, and cancer stem cell. They will substantially contribute to our understanding of OC pathogenesis. Given their resistance to the degradation of ribonucleases and availability in plasma exosomes, miRNAs may serve as emerging biomarkers for cancer detection, therapeutic assessment, and prognostic prediction. Being a messenger, exosomal miRNAs are crucial for the crosstalk between cancer cells and stromal cells in tumor microenvironment.
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Affiliation(s)
- Huilin Zhang
- Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Bingjian Lu
- Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
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32
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Kiel C, Berber P, Karlstetter M, Aslanidis A, Strunz T, Langmann T, Grassmann F, Weber BH. A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization. Int J Mol Sci 2020; 21:E2689. [PMID: 32294914 PMCID: PMC7216141 DOI: 10.3390/ijms21082689] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/09/2020] [Accepted: 04/10/2020] [Indexed: 12/15/2022] Open
Abstract
Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.
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Affiliation(s)
- Christina Kiel
- Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; (C.K.); (P.B.); (T.S.); (F.G.)
| | - Patricia Berber
- Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; (C.K.); (P.B.); (T.S.); (F.G.)
| | - Marcus Karlstetter
- Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, 50931 Cologne, Germany; (M.K.); (A.A.); (T.L.)
| | - Alexander Aslanidis
- Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, 50931 Cologne, Germany; (M.K.); (A.A.); (T.L.)
| | - Tobias Strunz
- Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; (C.K.); (P.B.); (T.S.); (F.G.)
| | - Thomas Langmann
- Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, 50931 Cologne, Germany; (M.K.); (A.A.); (T.L.)
| | - Felix Grassmann
- Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; (C.K.); (P.B.); (T.S.); (F.G.)
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 171 77 Stockholm, Sweden
| | - Bernhard H.F. Weber
- Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany; (C.K.); (P.B.); (T.S.); (F.G.)
- Institute of Clinical Human Genetics, University Clinics Regensburg, 93053 Regensburg, Germany
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Reinhold AK, Rittner HL. Characteristics of the nerve barrier and the blood dorsal root ganglion barrier in health and disease. Exp Neurol 2020; 327:113244. [PMID: 32057794 DOI: 10.1016/j.expneurol.2020.113244] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 01/17/2020] [Accepted: 02/09/2020] [Indexed: 12/14/2022]
Abstract
A variety of barriers ensures the protection of the peripheral nervous system from noxious blood-borne or surrounding stimuli. In this review, anatomy and functioning of the blood nerve barrier (BNB) and the blood DRG barrier (BDB) will be presented and key tight junction proteins described: ZO-1, claudin-1, -3, -5, -11, -12, -19, occludin, and tricellulin. Different diseases can lead to or be accompanied by nerve barrier disruption; impairment of nerve barriers in turn worsens pathology. Peripheral nerve injury, diabetic neuropathy and inflammatory polyneuropathy cause an increased permeability of BNB and BDB. Knowledge and understanding of these mechanisms might ultimately lead to the invention of drugs to control barrier function and help ameliorating neurological diseases.
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Affiliation(s)
- A K Reinhold
- Dept Anesthesiology, Center for Interdisciplinary Pain Medicine, University Hospitals Wuerzburg, Germany
| | - H L Rittner
- Dept Anesthesiology, Center for Interdisciplinary Pain Medicine, University Hospitals Wuerzburg, Germany.
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34
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The miRNAs Role in Melanoma and in Its Resistance to Therapy. Int J Mol Sci 2020; 21:ijms21030878. [PMID: 32013263 PMCID: PMC7037367 DOI: 10.3390/ijms21030878] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 01/20/2020] [Accepted: 01/26/2020] [Indexed: 12/11/2022] Open
Abstract
Melanoma is the less common but the most malignant skin cancer. Since the survival rate of melanoma metastasis is about 10–15%, many different studies have been carried out in order to find a more effective treatment. Although the development of target-based therapies and immunotherapeutic strategies has improved chances for patient survival, melanoma treatment still remains a big challenge for oncologists. Here, we collect recent data about the emerging role of melanoma-associated microRNAs (miRNAs) currently available treatments, and their involvement in drug resistance. We also reviewed miRNAs as prognostic factors, because of their chemical stability and resistance to RNase activity, in melanoma progression. Moreover, despite miRNAs being considered small conserved regulators with the limitation of target specificity, we outline the dual role of melanoma-associated miRNAs, as oncogenic and/or tumor suppressive factors, compared to other tumors.
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Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, Suciu N, Cretoiu SM, Voinea SC. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells 2020; 9:E276. [PMID: 31979244 PMCID: PMC7072450 DOI: 10.3390/cells9020276] [Citation(s) in RCA: 829] [Impact Index Per Article: 165.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 01/14/2020] [Accepted: 01/21/2020] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.
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Affiliation(s)
- Carmen Elena Condrat
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Dana Claudia Thompson
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Madalina Gabriela Barbu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Oana Larisa Bugnar
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Andreea Boboc
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Dragos Cretoiu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
| | - Nicolae Suciu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
- Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
- Department of Obstetrics and Gynecology, Polizu Clinical Hospital, Alessandrescu-Rusescu National Institute for Mother and Child Health, 020395 Bucharest, Romania
| | - Sanda Maria Cretoiu
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
| | - Silviu Cristian Voinea
- Department of Surgical Oncology, Prof. Dr. Alexandru Trestioreanu Oncology Institute, Carol Davila University of Medicine and Pharmacy, 252 Fundeni Rd., 022328 Bucharest, Romania;
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Zou W, Li X, Li C, Liu D, Lv Y, Yang Y, Ye N, Guo D, He S. Analysis of the relationship between MIR155HG variants and gastric Cancer susceptibility. BMC Gastroenterol 2020; 20:17. [PMID: 31959117 PMCID: PMC6972026 DOI: 10.1186/s12876-020-1169-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 01/13/2020] [Indexed: 12/29/2022] Open
Abstract
Background Gastric cancer is one of the most common cancers in the world and a major cause of cancer-related death. This study aims to determine whether genetic variations in MIR155HG could be associated with gastric cancer risk. Materials & methods A total of 506 gastric cancer patients and 500 healthy controls were enrolled in this study. Genotypes were examined with the MassARRAY platform and data management and analysis were conducted with the Typer Software. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with logistic regression adjusting for age and gender to evaluate the associations between SNPs with gastric cancer in genetic model analysis. Results The “CC” genotype of rs4143370 decreased the risk of gastric cancer in genotype model (p = 0.020) and recessive model (p = 0.018). Inversely, the “CC” genotype of rs1893650 increased the risk of gastric cancer in genotype model (p = 0.023) and recessive model (p = 0.014). Stratified analysis showed that rs11911469 was associated with an increased risk of gastric cancer only among the male group in the dominant model (p = 0.039) and additive model (p = 0.030). The haplotype analysis showed a strong linkage disequilibrium among these six SNPs (rs4143370, rs77699734, rs11911469, rs1893650, rs34904192 and rs928883). Conclusion This study confirmed the relationship between SNPs of MIR155HG and the gastric cancer risk among the Chinese Han population. Our data may provide a new perspective to understand the aetiology of gastric cancer.
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Affiliation(s)
- Wenjing Zou
- Department of gastroenterology, First Affiliate Hospital of Xi'an JiaoTong University, #227 West Yanta Road, Xi'an, 710061, Shaanxi Province, China.,Department of The fifth of Internal Medicine, Xi'an No5 Hospital, Xi'an, 710082, Shannxi, China
| | - Xu Li
- Department of The First of Internal Medicine, Tumor Hospital of Shannxi Province, The Affiliate Hospital of Medical College of Xi'an JiaoTong Univrsity, Xi'an, 710061, Shannxi, China
| | - Cheng Li
- Department of Geriatrics, Xi'an Central Hospital, Xi'an, 710003, Shannxi, China
| | - Dan Liu
- Department of Rheumatology, Xi'an No5 Hospital, Xi'an, 710082, Shannxi, China
| | - Yanyan Lv
- Department of Rheumatology, Xi'an No5 Hospital, Xi'an, 710082, Shannxi, China
| | - Ying Yang
- Department of The Second of Internal Medicine, Xi'an No5 Hospital, Xi'an, 710082, Shannxi, China
| | - Nan Ye
- Department of The Second of Internal Medicine, Xi'an No5 Hospital, Xi'an, 710082, Shannxi, China
| | - Dan Guo
- Department of gastroenterology, First Affiliate Hospital of Xi'an JiaoTong University, #227 West Yanta Road, Xi'an, 710061, Shaanxi Province, China
| | - Shuixiang He
- Department of gastroenterology, First Affiliate Hospital of Xi'an JiaoTong University, #227 West Yanta Road, Xi'an, 710061, Shaanxi Province, China.
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Ghafouri-Fard S, Shoorei H, Taheri M. miRNA profile in ovarian cancer. Exp Mol Pathol 2020; 113:104381. [PMID: 31954715 DOI: 10.1016/j.yexmp.2020.104381] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 01/15/2020] [Accepted: 01/16/2020] [Indexed: 12/29/2022]
Abstract
Ovarian cancer is a gynecological cancer with high mortality and a heterogeneous nature which complicates its early detection and primary prevention. Numerous studies have evaluated expression profile microRNAs (miRNAs) in tissue and serum samples of ovarian cancer patients to find appropriate biomarkers for this malignancy. Functional experiments also verified the oncogenic or suppressor effects of a number of miRNAs. miRNAs exert their role through degradation or inhibition of translation of the target mRNA. Through this regulatory function, they modulate numerous cellular processes which are ultimately associated with carcinogenesis. A number of miRNAs including miR-135a-3p, miR-200c, miR-216a and miR-340 regulate epithelial-mesenchymal transition program thus modulate invasiveness of ovarian cancer cell. Others have been shown to regulate some fundamental pathways in carcinogenesis such as mTOR and PI3K/AKT pathways. Such vast area of function of miRNAs in ovarian cancer has suggested them as putative therapeutic options for future years. In this review, we summarize the recent findings regarding the role of miRNAs in ovarian cancer pathogenesis, their application as biomarkers and the future perspectives of this research area.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Shoorei
- Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Shajari E, Mollasalehi H. Ribonucleic-acid-biomarker candidates for early-phase group detection of common cancers. Genomics 2020; 112:163-168. [DOI: 10.1016/j.ygeno.2018.08.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 08/06/2018] [Accepted: 08/31/2018] [Indexed: 02/08/2023]
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Zheng L, Jia R, Zhao J. Dexmedetomidine Regulates Proliferation, Apoptosis, Migration, and Invasion in Ovarian Cancer Cells via MiR-155-HIF-1α Axis. Med Sci Monit 2019; 25:10164-10172. [PMID: 31887107 PMCID: PMC6951111 DOI: 10.12659/msm.919112] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Dexmedetomidine (DMED) is widely used as an adjuvant anesthetic, but how DMED regulates biological behavior of OC cells remains an area of active research. This study investigated the mechanism by which DMED regulates the proliferation, apoptosis, migration, and invasion abilities of OC cells. MATERIAL AND METHODS We determined the optimal concentration of DMED for use in treating SKOV3 cells. The biological activities of DMED-treated SKOV3 cells following transfection with miR-155 inhibitor or si-HIF-1alpha were measured by CCK-8 assay, flow cytometry, wound healing assay, and Transwell assay. qRT-PCR and Western blot analysis were performed to assess the expression levels of apoptotic-related caspase-3 and Mcl-1. Luciferase reporter assay verified the targeting relationship of miR-155 and HIF-1alpha. RESULTS miR-155 was downregulated while HIF-1alpha was upregulated in SKOV3 cells. DMED dose-dependently reduced HIF-1alpha expression in SKOV3 cells, and upregulated the expression of miR-155. DMED inhibited the proliferation, migration and invasion abilities of OC cells, but also contributed to apoptosis of SKOV3 cells, while transfection of miR-155 inhibitor inhibited the effect of DMED on SKOV3 cells. In contrast, transfection with si-HIF-1alpha enhanced the effects of DMED on SKOV3 cells. HIF-1alpha was found to be a target gene of miR-155. CONCLUSIONS Our results suggest that DMED blocks cell proliferation, migration, and invasion and accelerates cell apoptosis in OC.
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Affiliation(s)
- Lihong Zheng
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China (mainland)
| | - Ruimei Jia
- Department of Pain Clinic, The First Affiliated Hospital Harbin Medical University, Harbin, Heilongjiang, China (mainland)
| | - Juan Zhao
- Department of Anesthesiology, Taixing People's Hospital, Taizhou, Jiangsu, China (mainland)
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MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα. Cell Death Dis 2019; 10:884. [PMID: 31767859 PMCID: PMC6877533 DOI: 10.1038/s41419-019-2124-x] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 12/13/2022]
Abstract
Recent studies have demonstrated that microRNA-155-5p (miR-155-5p) plays an essential role in the regulation of allergen-induced inflammation and is overexpressed in the skin of patients with atopic dermatitis (AD), although the mechanism is unknown. In this study, silencing miR-155-5p attenuated the thickening of the epidermis in AD model and reduced the infiltration of inflammatory cells and the secretion of Th2 cytokines. Protein kinase inhibitor α (PKIα) was identified as a direct target of miR-155-5p and correlated negatively with miR-155-5p in our AD model. Fluorescence in situ hybridization showed that miR-155-5p-expressing cells were predominantly present in the epidermis. When epithelial cells were transfected with an miR-155-5p inhibitor, the expression of PKIα, occludin, and CLDN16 increased and that of TSLP decreased significantly, whereas the overexpression of miR-155-5p resulted in the opposite changes. The increased expression of PKIα and tight junction (TJ) proteins, with reduced TSLP and IL-33, was also detected in miR-155-5p-blocked mice, in both the initial and elicitation stages of AD. The expression of TJ proteins also decreased when cells were transfected with PKIα siRNA. TJ proteins increased and TSLP and IL-33 decreased significantly after the overexpression of PKIα. Our data provide the first evidence that miR-155-5p is critical for the allergic inflammation in a mouse model of AD by directly regulating PKIα and thus epithelial TJ expression. These findings suggest new therapeutic strategies that target miR-155-5p in patients with allergic disorders.
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Satapathy S, Kumar C, Singh RK. MicroRNAs as Key Regulators of Ovarian Cancers. CELL MEDICINE 2019; 11:2155179019873849. [PMID: 32634196 PMCID: PMC6732848 DOI: 10.1177/2155179019873849] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 07/27/2019] [Accepted: 08/13/2019] [Indexed: 12/13/2022]
Abstract
The tumor microenvironment can be realistically viewed as an active battle ground between
the host immune system and the growing tumor cells. This reactive space surrounding the
tumor possesses several possibilities and facilitates the progression of a tumor from a
neoplastic stage to that of metastasis. The contemporary approach of understanding the
cancer biology from a “within the cell” perspective has been largely challenged with
complex and intricate “outside the cell” events. Thus understanding the biology of the
tumor microenvironment has been of scientific and clinical interest. Small non-coding
microRNAs with a pleotropic and wide range of cellular gene targets can be reasonably
hypothesized to regulate the events of carcinogenesis and progression. MicroRNAs have been
investigated in different cancer models, and evidence of their involvement in the
regulation of the tumor microenvironment has been of much interest. In particular, a major
interest has been exploring the role of the tumor microenvironment in regulating the
interaction of cancer cells with surrounding stromal components and the effect of such
interactions on the cancer cells. Fine-tuned regulation by these microRNAs extends our
contemporary understanding of these small biomolecules in epigenetic regulations. This
review focuses on microRNAs that are dysregulated in ovarian carcinomas, their effect on
the components of the tumor microenvironment, and the correlation of their heterogeneous
expression profiles with disease severity and prognosis in patients. In addition, this
paper also discusses the differential expression of exosomal microRNAs that are known to
link the cancer cell with its microenvironment, facilitating the development of an
improved prognostic/diagnostic marker and effective therapeutic regime.
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Affiliation(s)
- Sandeep Satapathy
- Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India
| | - Chanchal Kumar
- Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
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Phattarataratip E, Sappayatosok K. The Significance of Relative Claudin Expression in Odontogenic Tumors. Head Neck Pathol 2019; 14:480-488. [PMID: 31473941 PMCID: PMC7235137 DOI: 10.1007/s12105-019-01072-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 08/28/2019] [Indexed: 12/11/2022]
Abstract
Claudins are integral to the structure and function of tight junctions. Altered claudin expression has been shown to affect disease behavior and patient prognosis in various neoplasms. The objectives of this study were to analyze the claudin-1, -4 and -7 expression in odontogenic tumors and characterize their expression pattern in distinct tumor cell types in relation to the recurrence potential. Sixty-nine cases of odontogenic tumors, including 43 ameloblastomas (AM), 17 adenomatoid odontogenic tumors (AOT), 6 ameloblastic fibromas (AF) and 3 ameloblastic carcinomas (AC) were investigated for claudin-1, -4 and -7 expression immunohistochemically. The staining was analyzed semi-quantitatively and categorized into 4 levels, based on the percentage of positively stained neoplastic epithelial cells. Claudin-1 was expressed in all AOT and AF cases, whereas most AC (66.7%) showed no expression. The claudin-1 staining was moderate-to-intense in the odontogenic epithelium of AF. In contrast, its staining of ameloblast-like cells and stellate reticulum-like cells in AM was weak. Claudin-7 expression was noted in all tumor types studied, while the expression of claudin-4 was limited and mainly localized in the squamous differentiated cells of AM and AC. AM showed significantly higher claudin-4, but lower claudin-7 expression than AOT. In addition, AC showed diminished claudin-1 immunoreactivity, compared to AOT. Low claudin-1 expression in AM was significantly associated with the increased clinical recurrence. The loss of claudin-1 may underlie the locally invasive nature of AM.
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Affiliation(s)
- Ekarat Phattarataratip
- Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Henri-Dunant Road, Pathumwan, Bangkok, 10330 Thailand
| | - Kraisorn Sappayatosok
- Faculty of Dental Medicine, Rangsit University, 52/347 Muang-Ake, Phaholyothin Road, Lak-Hok, Muang, 12000 Pathumthani Thailand
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Tong L, Ao Y, Zhang H, Wang K, Wang Y, Ma Q. Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR-155-5p. Cancer Med 2019; 8:4782-4791. [PMID: 31250987 PMCID: PMC6712470 DOI: 10.1002/cam4.2350] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 05/26/2019] [Accepted: 05/29/2019] [Indexed: 12/12/2022] Open
Abstract
Purpose In the present study, we evaluated the expression and function of human long noncoding RNA (lncRNA) activated by DNA damage (NORAD) in human epithelial ovarian cancer (EOC). Methods NORAD expression was evaluated by qRT‐PCR in EOC cell lines and in situ EOC clinical samples. Lentivirus‐mediated NORAD downregulation was conducted in OVCAR‐3 and ES‐2 cells, and its effect on cancer cell proliferation, bufalin chemoresistance, cell‐cycle transition in vitro, and xenotransplantation in vivo were examined, respectively. The likelihood of an lncRNA‐microRNA (miRNA) signaling pathway was examined by probing the possible downstream competing target of NORAD, hsa‐miR‐155‐5p. Moreover, hsa‐miR‐155‐5p was knocked down in NORAD‐downregulated EOC cells to functionally evaluate the correlation between NORAD and hsa‐miR‐155‐5p in EOC. Results We found that NORAD was substantially upregulated in both EOC cell lines and human tumors. In OVCAR‐3 and ES‐2 cells, lentivirus‐mediated NORAD downregulation had significant anticancer effects, as it suppressed cell proliferation, decreased bufalin chemoresistance, arrested cell‐cycle transition, and inhibited xenograft growth. Also, hsa‐miR‐155‐5p was confirmed to be the competing target of NORAD in EOC, and its knockdown in OVCAR‐3 and ES‐2 cells reversed the NORAD downregulation‐induced anticancer functions. Conclusions NORAD is upregulated in EOC. Inhibition of NORAD, possibly through endogenously competing against hsa‐miR‐155‐5p, can be a new tumor‐suppressing strategy in EOC.
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Affiliation(s)
- Lingling Tong
- Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yu Ao
- Department of Pediatric Intensive Care Unit (PICU), The First Hospital of Jilin University, Changchun, China
| | - Hejia Zhang
- Department of Ultrasonography, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Kun Wang
- Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yunyun Wang
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Qingjie Ma
- Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Changchun, China
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Michaille JJ, Awad H, Fortman EC, Efanov AA, Tili E. miR-155 expression in antitumor immunity: The higher the better? Genes Chromosomes Cancer 2019; 58:208-218. [PMID: 30382602 DOI: 10.1002/gcc.22698] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 10/25/2018] [Accepted: 10/28/2018] [Indexed: 12/15/2022] Open
Abstract
MicroRNAs are small noncoding RNAs that modulate gene expression either directly, by impairing the stability and/or translation of transcripts that contain their specific target sequence, or indirectly through the targeting of transcripts that encode transcription factors, factors implicated in signal transduction pathways, or epigenetic regulators. Abnormal expression of micro-RNAs has been found in nearly all types of pathologies, including cancers. MiR-155 has been the first microRNA to be implicated in the regulation of the innate and adaptative immune responses, and its expression is either increased or decreased in a variety of liquid and solid malignancies. In this review, we examine the oncogenic and antitumor potentials of miR-155, with special emphasize on its dose-dependent effects. We describe the impact of miR-155 levels on antitumor activity of lymphocytes and myeloid cells. We discuss miR-155 dose-dependent effects in leukemias and analyze results showing that miR-155 intermediate levels tend to be detrimental, whereas high levels of miR-155 expression usually prove beneficial. We also examine the beneficial effects of high levels of miR-155 expression in solid tumors. We discuss the possible causal involvement of miR-155 in leukemias and dementia in individuals with Down's syndrome. We finally propose that increasing miR-155 levels in immune cells might increase the efficiency of newly developed cancer immunotherapies, due to miR-155 ability to target transcripts encoding immune checkpoints such as cytotoxic T lymphocyte antigen-4 or programmed death-ligand 1.
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Affiliation(s)
- Jean-Jacques Michaille
- BioPerox-IL, Université de Bourgogne-Franche Comté (EA 7270), Dijon, France.,Department of Cancer Biology and Genetics, Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Hamdy Awad
- Department of Anesthesiology, Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Emily C Fortman
- Department of Cancer Biology and Genetics, Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Alexander A Efanov
- Department of Anesthesiology, Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Esmerina Tili
- Department of Cancer Biology and Genetics, Wexner Medical Center, The Ohio State University, Columbus, Ohio.,Department of Anesthesiology, Wexner Medical Center, The Ohio State University, Columbus, Ohio
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Zheng YF, Luo J, Gan GL, Li W. Overexpression of microRNA-98 inhibits cell proliferation and promotes cell apoptosis via claudin-1 in human colorectal carcinoma. J Cell Biochem 2019; 120:6090-6105. [PMID: 30506722 DOI: 10.1002/jcb.27895] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 09/24/2018] [Indexed: 02/05/2023]
Abstract
Colorectal carcinoma (CRC) is a major cause of cancer-related deaths worldwide, and investigations on novel targets are imperative. MiR-98 has been reported to act as a tumor suppressor in several cancers. To evaluate miR-98 as a novel anticancer molecule for CRC, examinations to validate whether miR-98 conferred an inhibiting effect on proliferation, migration, and invasion were performed. The microarray-based gene expression profiling involving CRC was used to identify the differentially expressed genes. The potential relationship between miR-98 and CLDN1 was analyzed by cell experimentation. Then, the CRC cells were transfected with miR-98 mimic or miR-98 inhibitor to investigate the potential effect of miR-98 overexpression and depletion on CRC cell proliferation, migration, invasion, and apoptosis. The expressions of CLDN1, Bcl-2 associated protein x (Bax), runt-related transcription factor 3 (RUNX3), B-cell lymphoma 2 (Bcl-2), C-myc, and proliferating cell nuclear antigen (PCNA) were determined. The downregulated miR-98 along with an upregulated CLDN1 was observed in CRC, in which miR-98 could target to regulate CLDN1. The overexpression of miR-98 or silencing of CLDN1 was shown to increase the expression of Bax and RUNX3 along with promoted cell apoptosis and arrested cells in G1 phase, while decreasing the expression of CLDN1, Bcl-2, C-myc, and PCNA with suppressed proliferation, migration, and invasion. Collectively, the current study supports the notion that miR-98 plays an inhibitory role in human CRC cell proliferation, migration, and invasion and act as a contributor for cell apoptosis by downregulating CLDN1. The current study highlights a potential future strategy to help prevent the development of CRC.
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Affiliation(s)
- Yi-Feng Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Jie Luo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Guo-Lian Gan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Wei Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
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Ekiz HA, Huffaker TB, Grossmann AH, Stephens WZ, Williams MA, Round JL, O'Connell RM. MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. JCI Insight 2019; 4:126543. [PMID: 30721153 DOI: 10.1172/jci.insight.126543] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 01/31/2019] [Indexed: 12/27/2022] Open
Abstract
miR-155 has recently emerged as an important promoter of antitumor immunity through its functions in T lymphocytes. However, the impact of T cell-expressed miR-155 on immune cell dynamics in solid tumors remains unclear. In the present study, we used single-cell RNA sequencing to define the CD45+ immune cell populations at different time points within B16F10 murine melanoma tumors growing in either wild-type or miR-155 T cell conditional knockout (TCKO) mice. miR-155 was required for optimal T cell activation and reinforced the T cell response at the expense of infiltrating myeloid cells. Further, myeloid cells from tumors growing in TCKO mice were defined by an increase in wound healing genes and a decreased IFN-γ-response gene signature. Finally, we found that miR-155 expression predicted a favorable outcome in human melanoma patients and was associated with a strong immune signature. Moreover, gene expression analysis of The Cancer Genome Atlas (TCGA) data revealed that miR-155 expression also correlates with an immune-enriched subtype in 29 other human solid tumors. Together, our study provides an unprecedented analysis of the cell types and gene expression signatures of immune cells within experimental melanoma tumors and elucidates the role of miR-155 in coordinating antitumor immune responses in mammalian tumors.
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Affiliation(s)
| | | | - Allie H Grossmann
- Division of Anatomic Pathology, Department of Pathology, University of Utah.,Huntsman Cancer Institute, University of Utah Health Sciences Center, and.,ARUP Laboratories, University of Utah, Salt Lake City, Utah, USA
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Reinhold AK, Yang S, Chen JTC, Hu L, Sauer RS, Krug SM, Mambretti EM, Fromm M, Brack A, Rittner HL. Tissue plasminogen activator and neuropathy open the blood-nerve barrier with upregulation of microRNA-155-5p in male rats. Biochim Biophys Acta Mol Basis Dis 2019; 1865:1160-1169. [PMID: 30625382 DOI: 10.1016/j.bbadis.2019.01.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 11/30/2018] [Accepted: 01/04/2019] [Indexed: 12/14/2022]
Abstract
The blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels is sealed by tight junction proteins. BNB alterations are a crucial factor in the pathogenesis of peripheral neuropathies. However, barrier opening, e.g. by tissue plasminogen activator (tPA), can also facilitate topical application of analgesics. Here, we examined tPA both in the pathophysiology of neuropathy-induced BNB opening or via exogenous application and its effect on the cytoplasmatic tight junction protein anchoring protein, zona occludens-1 (ZO-1), the adherens molecule JAM-C and microRNA(miR)-155-5p. Specifically, we investigated whether tPA alone and barrier opening lead to pain behavioral changes, i.e. hyperalgesia, or whether these effects require further factors. Male Wistar rats underwent chronic constriction injury (CCI) or were treated by a single perisciatic application of recombinant (r)tPA. CCI elicited mechanical allodynia, tPA mRNA upregulation, macrophage invasion, BNB leakage for large molecule tracers, downregulation of ZO-1 and JAM-C mRNA/protein, and a loss of immunoreactivity of both in perineurium and endoneurial cells. Similarly, after perisciatic rtPA injection, ZO-1 and JAM-C mRNA as well as cytosolic/membrane protein and ZO-1 immunoreactivity were downregulated, and the BNB was opened. Neither mechanical hypersensitivity nor macrophage infiltration was observed after rtPA in contrast to CCI. Mechanistically, miR-155-5p, which is known to destabilize barriers and tight junction proteins like claudin-1 and ZO-1, was increased in CCI and to lesser extent after rtPA application. In summary, tPA transiently opens the BNB possibly via miR-155-5p. However, tPA does not provoke allodynia in the absence of a neuropathic stimulus like a ligation or inflammation.
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Affiliation(s)
- Ann-Kristin Reinhold
- Dept. of Anesthesiology, University Hospital of Würzburg, 97080 Würzburg, Germany
| | - Shaobing Yang
- Dept. of Anesthesiology, University Hospital of Würzburg, 97080 Würzburg, Germany; Dept. of Anesthesiology and Pain Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China
| | | | - Liu Hu
- Dept. of Anesthesiology, University Hospital of Würzburg, 97080 Würzburg, Germany; Dept. of Anesthesiology and Pain Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China
| | - Reine-Solange Sauer
- Dept. of Anesthesiology, University Hospital of Würzburg, 97080 Würzburg, Germany
| | - Susanne M Krug
- Institute of Clinical Physiology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany
| | - Egle M Mambretti
- Dept. of Anesthesiology, University Hospital of Würzburg, 97080 Würzburg, Germany
| | - Michael Fromm
- Institute of Clinical Physiology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany
| | - Alexander Brack
- Dept. of Anesthesiology, University Hospital of Würzburg, 97080 Würzburg, Germany
| | - Heike L Rittner
- Dept. of Anesthesiology, University Hospital of Würzburg, 97080 Würzburg, Germany.
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Zhou Y, Wang X, Liu Z, Huang X, Li X, Cheng K, Jiang X. Prognostic role of microRNA-155 expression in gliomas: A meta-analysis. Clin Neurol Neurosurg 2018; 176:103-109. [PMID: 30554090 DOI: 10.1016/j.clineuro.2018.12.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 11/27/2018] [Accepted: 12/06/2018] [Indexed: 12/20/2022]
Abstract
Recent studies have reported that microRNA-155 (miR-155) is linked to the clinical outcomes of many tumors. However, its role in prognosis of gliomas remains unclear. This meta-analysis aims to evaluate the prognostic value of miR-155 in the survival of patients with gliomas. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) were pooled with random effects or fixed effects models on the basis of heterogeneity. Subgroup analysis and sensitivity analysis were performed to elucidate the possible confounding factors and investigate the source of heterogeneity. In addition, we assessed publication bias using the Begg's funnel plots, Egger's test, and Begg's test. Only non-laboratory studies were considered for our analysis. 9 studies from 6 articles containing 1259 glioma patients were included. The pooled HR of elevated miR-155 for OS in patients with gliomas was 1.40 (95%CI [1.19-1.63], P < 0.001) (I-squared = 52.4%, P = 0.032) suggesting that miR-155 might be a promising biomarker for the prognosis of gliomas in future clinical applications.
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Affiliation(s)
- Yan Zhou
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Xuan Wang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Zhen Liu
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Xing Huang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Xudong Li
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Kai Cheng
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Xiaobing Jiang
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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Harquail J, LeBlanc N, Landry C, Crapoulet N, Robichaud GA. Pax-5 Inhibits NF-κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors. J Mammary Gland Biol Neoplasia 2018; 23:177-187. [PMID: 30032344 DOI: 10.1007/s10911-018-9404-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 07/05/2018] [Indexed: 12/17/2022] Open
Abstract
Pax-5, an essential transcription factor in B cell development, is aberrantly expressed in various B cell cancer lesions and solid tumors such as breast carcinoma. We have recently shown that Pax-5 regulates NF-κB activity which lead to the modulation of breast cancer phenotypic features (EMT-MET). NF-κB is known as a central mediator in inflammation, stress response as well as being a gatekeeper of pro-tumorigenic activity. However, little is known as to how Pax-5 affects this modulation. We thus turned our attention to microRNAs as potential regulatory effectors. In this study, we set out to elucidate the regulatory network between differential Pax-5 expression and NF-κB activity which dictate breast cancer malignancy. Through next-generation sequencing (NGS) of breast cancer cells conditionally expressing Pax-5, we profile significantly upregulated microRNAs; including microRNA-155, a known regulator of pathological processes and suppressor of malignant growth. Through the conditional expression of microRNA-155 in breast cancer models, we identify and validate IKKε (IKBKE) as a downstream target and an essential effector of Pax-5-mediated suppression of NF-κB signaling. Using rescue experiments, we also confirm that Pax-5 modulates NF-κB activity via IKKε downregulation. Interestingly, we also show that microRNA-155, in turn, supresses Pax-5 expression, indicative of an auto-regulatory feedback loop. Altogether, we demonstrate that Pax-5 inhibits NF-κB signalling through the regulation of microRNA-155 and its downstream target IKKε. The elucidation of this signaling network is relevant as Pax-5 and NF-κB are potent transcriptional regulators of breast cancer aggressivity. In addition, IKKε is relevant oncogene aberrantly expressed in 30% of breast carcinomas. Further insight into the regulatory pathways of breast cancer progression will eventually identify strategic therapeutic and prognostic targets to improve cancer patient outcome.
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Affiliation(s)
- Jason Harquail
- Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada
| | - Nicolas LeBlanc
- Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada
| | - Carine Landry
- Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada
| | - Nicolas Crapoulet
- Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada
| | - Gilles A Robichaud
- Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, Canada.
- Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
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50
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El-Balat A, Schmeil I, Gasimli K, Sänger N, Karn T, Ahr A, Becker S, Arsenic R, Holtrich U, Engels K. Claudin-1 is linked to presence of implants and micropapillary pattern in serous borderline epithelial tumours of the ovary. J Clin Pathol 2018; 71:1060-1064. [PMID: 30171086 DOI: 10.1136/jclinpath-2018-205292] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 08/01/2018] [Accepted: 08/02/2018] [Indexed: 01/13/2023]
Abstract
AIMS Expression of Claudin-1 has been associated with prognosis in several cancers. Here we investigated the expression pattern of Claudin-1 in borderline tumours of the ovary (BOT). METHODS We analysed a cohort of 114 cases of borderline tumour (BOT). Claudin-1 expression was studied by immunohistochemistry using a polyclonal antibody and was compared with clinical and histopathological characteristics. RESULTS Strong Claudin-1 expression was found in 30 cases (26.3%) independent of histological subtype. Expression was significantly less frequent in International Federation of Gynecology and Obstetrics (FIGO) stage I (p= 0.045), while the presence of microinvasion did not correlate with Claudin-1 expression. In contrast, we detected a highly significant association of Claudin-1 expression with the presence of peritoneal implants (p=0.003) and micropapillary pattern (p=0.047), which are features exclusively seen in serous BOT. Moreover, when we restricted our analysis to the subtype of serous BOT, the association of Claudin-1 expression with peritoneal implants (p<0.001) and micropapillary pattern (p =0.003) remained highly significant. CONCLUSIONS In conclusion, Claudin-1 expression is associated with the presence of peritoneal implants and micropapillary pattern, which have been shown to be associated with poor prognosis. We speculate that overexpression of Claudin-1 might be linked to the mitogen-activated protein kinase pathway activation in BOT and suggest further studies to define its prognostic and potential therapeutic value.
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Affiliation(s)
- Ahmed El-Balat
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Iryna Schmeil
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Khayal Gasimli
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Nicole Sänger
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Thomas Karn
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Andre Ahr
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Sven Becker
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Ruza Arsenic
- Institute of Pathology, Charite University Hospital, Berlin, Germany
| | - Uwe Holtrich
- Department of Obstetrics and Gynecology, University Hospital Frankfurt, Frankfurt, Germany
| | - Knut Engels
- Center for Pathology, Cytology and Molecular Pathology, Neuss, Germany
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