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  1. Home
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Browsing by Subject "MicroRNA"

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    Big roles of microRNAs in tumorigenesis and tumor development
    (F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Tie, Jun; Fan, Daiming
    MicroRNAs (miRNAs) are a class of endogenous non-protein-coding small RNAs that are evolutionarily conserved and widely distributed among species. Their major function is to negatively regulate target gene expression. A single miRNA can regulate multiple target genes, indicating that miRNAs may regulate multiple signaling pathways and participate in a variety of physiological and pathological processes. Currently, approximately 50% of identified human miRNA-coding genes are located at tumor-related fragile chromosome regions. Abnormal miRNA expression and/or mutations have been found in almost all types of malignancies. These abnormally expressed miRNAs play roles similar to tumor suppressor genes or oncogenes by regulating the expression and/or function of tumor-related genes. Therefore, miRNAs, miRNA target genes, and the genes regulating miRNAs form a regulatory network with miRNAs in the hub. This network plays a pivotal role in tumorigenesis and tumor development.
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    Cancer-related microRNAs and their role as tumor suppressors and oncogenes in hepatocellular carcinoma
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Gailhouste, Luc; Ochiya, Takahiro
    MicroRNAs (miRNAs) have emerged as key factors involved in several biological processes, including development, differentiation, cell proliferation, and tumorigenesis. In hepatocellular carcinoma (HCC), miRNAs frequently present aberrant expression profiles, which make them potentially attractive for diagnostic or prognostic applications. Currently, accumulating evidence is indicating the role of miRNAs as tumor suppressors or oncogenes in hepatic malignancies. In particular, comprehensive studies have made possible a better understanding of HCC behavior, such as tumor growth, response to therapies, metastatic potential, or recurrence, regarding the altered expression of cancerrelated miRNAs. Based on these findings, efforts are under way to define new markers for liver cancer in both invasive (hepatic biopsy or tumor resection) and noninvasive (circulating miRNAs in blood serum) ways. Due to their implication in the control of various cell processes altered in HCC, cancer-related miRNAs also offer encouraging perspectives for the development of innovative cancer therapies. In this article, we review the importance of miRNA deregulation in HCC progression and the role of these small non-coding RNAs as tumor suppressors and oncogenes. The significance of miRNAs in HCC diagnosis and miRNA-based therapeutic strategies is then discussed.
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    From Barrett metaplasia to esophageal adenocarcinoma: the molecular background
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Saraggi, Deborah; Fassan, Matteo; Bornschein, Jan; Farinati, Fabio; Realdon, Stefano; Valeri, Nicola; Rugge, Massimo
    The molecular landscape of Barrett’s esophagus and Barrett-related neoplastic lesions is still far from being completely elucidated. Both in vitro and in vivo studies pinpointed the pathogenetic role of different morphogenic pathways (the para-homeobox, the Notch and the Sonic Hedgehog families in particular) implicated in the acquisition of the metaplastic phenotype of the esophageal mucosa. On the other hand, the most common genetic alterations observed during Barrett's carcinogenesis include disorders of major regulators of the cell cycle, as well as deregulation of the TGF-β/Smad and receptor tyrosine kinases signalling pathways. Recent comprehensive mutational profiling studies identified that the inactivation of the TP53 and of the SMAD4 tumour suppressor genes occurred in a stage-specific manner, confined to (high grade) dysplastic and neoplastic lesions, respectively. The next step will be the correlation of these findings into multidisciplinary diagnostic approaches integrating endoscopy, histology, molecular profiling and liquid biopsies. This will allow the introduction of innovative strategies for secondary prevention of esophageal adenocarcinoma based on biological rationales, and the implementation of potential novel therapeutic targets.
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    Long non-coding RNA-KCNQ1OT1 mediates miR-423-5p/microfibril-associated protein 2 axis in colon adenocarcinoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Yin, Xunhai; Jiang, Amín; Ma, Zhibin; Lu, Xi; Li, Dongyue; Chen, Yingying
    Backgrounds. Long non-coding RNAs (lncRNAs) function as competing endogenous RNAs (ceRNAs) that contribute to carcinogenesis. Herein, we plan to explore whether lncRNA KCNQ1OT1 modulated miR-423-5p/microfibril-associated protein 2 (MFAP2) signaling axis is implicated in the progression of human colon adenocarcinoma. Material and methods. Clinical specimens were collected for histologic examination and gene expression analysis. In vitro experimental measurements, including CCK8, transwell and TUNEL staining, were performed to evaluate cell proliferation, migration and apoptosis. Results. up-regulation of KCNQ1OT1 and MFAP2 and down-regulation of miR-423-5p in COAD tissues were substantiated by The Cancer Genome Atlas (TCGA) database and our clinical specimens. In vitro experimental measurements exhibited that knockdown of KCNQ1OT1 facilitated miR-423-5p expression and inhibited MFAP2 expression, simultaneously. Transfection of si-KCNQ1OT1, miR-423-5p mimics or si-MFAP2 had the ability to repress malignant phenotypes of COAD cells. Intriguingly, overexpression of MFAP2 restrained si-KCNQ1OT1- or miR-423-5p mimics-induced the inhibition of cell proliferation and migration and elevation of the apoptotic proportion of COAD cells. Conclusions. KCNQ1OT1 serves as a molecular sponge of miR-423-5p to accelerate the expression of MFAP2 that may be involved in the development of COAD. Our findings present a novel signaling axis KCNQ1OT1/miR-423-5p/MFAP2, which provides a theoretical basis and therapeutic target for the treatment of COAD.
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    Micro-RNA signature of lymphovascular space involvement in type 1 endometrial cancer
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Canlorbe, Geoffroy; Castela, Mathieu; Bendifallah, Sofiane; Wang, Zhe; Lefevre, Marine; Chabbert Buffet, Nathalie; Aractingi, Selim; Daraï, Emile; Méhats, Céline; Ballester, Marcos
    Objective. Lymphovascular space involvement (LVSI) is a major prognostic factor in type 1 endometrial cancer (EC). However, its use has been criticized because of poor subjectivity. MicroRNA signatures have recently been linked to EC pathologic characteristics. The aim of this study was to evaluate whether microRNA profiles of type 1 EC can be related to LVSI status and used as a tool to adapt therapy. Study Design. MicroRNA expression was assessed by chip analysis and qRT-PCR in 12 formalin-fixed paraffin-embedded grade 2 EC specimens with positive LVSI and in 12 specimens with negative LVSI. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. Results. The expression levels of microRNAs 34c5p, -23b-5p, and 23c were significantly lower in the EC with positive LVSI compared to those with negative LVSI. Women with a microRNA-34c-5p fold change <0.15 were more likely to have positive LVSI status (92.3%) compared with those with a microRNA-34c-5p fold change >0.15 (0.0%), p<0.001. Furthermore, women with a microRNA-23b-5p fold change <0.51 were more likely to have positive LVSI status (90.0%) compared with those with a microRNA-23b-5p fold change >0.51 (21.4%), p=0.003. Conclusion. This was the first study to investigate the relative expression of microRNA in type 1 EC according to LVSI status. This microRNA expression profile may provide a basis for further study of the microRNA function in EC, and be used as a diagnostic tool for LVSI status.
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    MicroRNA in prostate cancer: Practical aspects
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Patil, Pallavi A.; Magi-Galluzzi, Cristina
    In the last decade, microRNAs (miRNAs) have emerged as biomarkers for cancer diagnosis, prognosis, therapy and prediction of treatment response and have earned a promising role in prostate cancer (PCa) management. A plethora of studies have been conducted on miRNA expression in PCa compared to non-neoplastic prostatic tissue, in PCa of different histologic grades and pathologic stages, in castration resistance prostate cancer (CRPC), in metastatic disease and in response to therapy, with evidence pointing towards distinctive miRNAs differentially expressed in each of these phases. In addition to tissue, MiRNA can be detected in blood, serum, and urine. The aim of this review is to survey studies conducted on human prostate tissue and biofluids and to consolidate trustworthy data on the role of miRNA in the occurrence and progression of PCa, with a delineation of differentially expressed miRNAs and an analysis of their association with PCa prognosis, progression to CRPC and metastatic disease, as well as their correlation with response to chemotherapy and hormonal therapy. Changes in circulating miRNAs may represent potentially useful non-invasive biomarkers for PCa diagnosis, staging and prediction of outcome.
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    MicroRNA regulation in an animal model of acute ocular hypertension
    (John Wiley & Sons Ltd., 2017-02-01) Wang, Jiawei; Valiente Soriano, Francisco Javier; Nadal-Nicolás, Francisco Manuel; Rovere, Giuseppe; Chen, Shida; Huang, Wenbin; Agudo Barriuso, Marta; Jonas, Jost B.; Vidal Sanz, Manuel; Zhang, Xiulan; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Medicina
    Purpose: To analyse miRNA regulation in a rat model of acute ocularhypertension (AOH). Methods: Acute ocular hypertension (AOH) was induced in the left eye of adult albino rats by inserting a cannula connected with a saline container into the anterior chamber. The contralateral eye served as a control. Seven days later, animals were killed. Retinas were used either for quantitative analysis of retinal ganglion cells (RGCs) and microglial cells or for miRNA array hybridization, qRT-PCR and Western blotting. Results: Anatomically, AOH caused axonal degeneration, a significant loss of RGCs and a significant increase in microglial cells in the ganglion cell layer. The miRNAs microarray analysis revealed 31 differentially expressed miRNAs in the AOH versus control group, and the regulation of 12 selected microRNAs was further confirmed by qRT-PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated miRNAs. Of particular interest was the inflammatory pathway signalled by mitogen-activated protein kinases (MAPKs). In agreement with the in silico analysis, p38 MAP kinase, tumour necrosis factor-alpha (TNF-a) and iNOS proteins were significantly upregulated in the AOH retinas. Conclusions: Acute IOP elevation led to changes in the expression of miRNAs, whose target genes were associated with the regulation of microglia-mediated neuroinflammation or neural apoptosis. Addressing miRNAs in the process of retinal ischaemia and optic nerve damage in association with high IOP elevation may open new avenues in preventing retinal ganglion cell apoptosis and may serve as target for future therapeutic regimen in acute ocular hypertension and retinal ischaemic conditions.
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    MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: critical issues to discern between modulatory effects and potential artefacts
    (Wiley, Wiley-VCH Verlag, 2015-07-20) Núñez Sánchez, María A.; Dávalos, Alberto; González-Sarrías, Antonio; Casas-Agustench, Patricia; Visioli, Francesco; Monedero Saiz, Tamara; García Talavera, Noelia V.; Gómez Sánchez, María B.; Sánchez-Álvarez, Carmen; García-Albert, Ana M.; Rodríguez-Gil, Francisco J.; Ruiz-Marín, Miguel; Pastor Quirante, Francisco A.; Martínez Díaz, Francisco; Tomás-Barberán, Francisco A.; García-Conesa, María Teresa; Espín, Juan Carlos; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
    Scope: MicroRNAs (miRs) are proposed as colorectal cancer (CRC) biomarkers. Pomegranate ellagic acid and their microbiota metabolites urolithins exert anticancer effects in preclinical CRC models, and target normal and malignant colon tissues in CRC patients. Herein, we investigated whether the intake of pomegranate extract (PE) modified miRs expression in surgical colon tissues versus biopsies from CRC patients. Methods and results: We conducted a randomized, double-blind, controlled trial. Thirty-five CRC patients consumed 900 mg PE daily before surgery. Control CRC patients (no PE intake, n = 10) were included. Our results revealed: (1) significant differences for specific miRs between malignant and normal tissues modifiable by the surgical protocols; (2) opposed trends between -5p and -3p isomolecules; (3) general induction of miRs attributable to the surgery; (4) moderate modulation of various miRs following the PE intake, and (5) no association between tissue urolithins and the observed miRs changes. Conclusion: PE consumption appears to affect specific colon tissue miRs but surgery critically alters miRs levels hindering the discrimination of significant changes caused by dietary factors and the establishment of genuine differences between malignant and normal tissues as biomarkers. The components responsible for the PE effects and the clinical relevance of these observations deserve further research.
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    MIR376 family and cancer
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Tekirdag, Kumsal Ayse; Akkoc, Yunus; Kosar, Ali; Gozuacik, Devrim
    MicroRNAs (miRNAs) are endogenous noncoding small RNAs that negatively regulate gene expression at the post-transcriptional level. They have been implicated in several fundamental biological processes including development, differentiation, apoptosis and stem cell maintenance. There is increasing evidence that microRNAs also play roles in cellular transformation and carcinogenesis by acting either as tumor suppressors or oncogenes. Recent studies introduced MIR376 as an important microRNA family for cancer formation and progression. The MIR376 family is located on human chromosome 14 and it has several members containing identical or similar seed sequences. Biological roles of family members were studied in different cancer settings, including gliomas, leukemia, breast and ovarian cancers. Furthermore, two MIR376 family members, namely MIR376A and MIR376B were implicated in the regulation of macroautophagy (autophagy herein). Since autophagy dysregulation underlies various diseases including cancer, it is essential to understand the role of the MIR376 family in this context. In this article, we summarize the miRNA-cancer connection, and review accumulating data about the involvement of the MIR376 family in cancer biology.
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    miRNA-21 and miRNA-27b expression in saliva of patients with oral lichen planus: a systematic review
    (MDPI, 2025-06-18) Di Stasio, Dario; Fiori, Fausto; Romano, Antonio; Palmieri, Annalisa; Mosca, Laura; Ruiz Roca, Juan Antonio; López Jornet, María Pía; Lucchese, Alberta; Dermatología, Estomatología, Radiología y Medicina Física; Facultad de Medicina
    Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa with a recognized risk of malignant transformation. MicroRNAs, particularly miRNA-21 and miRNA-27b, have been implicated in the pathogenesis and progression of various diseases, including OLP. Their altered expression in saliva may provide diagnostic and prognostic insights for this condition. This systematic review examines the expression profiles of miRNA-21 and miRNA-27b in the saliva of OLP patients to assess their potential as biomarkers. The review was conducted in accordance with PRISMA guidelines and was registered in the PROSPERO database. A comprehensive search was conducted in PubMed, Embase, and Scopus using specific keywords. Retrieved titles and abstracts were screened based on predefined eligibility criteria, and relevant studies were analyzed. The initial search identified 71 studies. After screening, 17 abstracts were selected for full-text review. Following evaluation, 11 studies were excluded, resulting in 6 studies being included. Findings indicate a consistent upregulation of miRNA-21 and a downregulation of miRNA-27b in OLP saliva samples. These alterations suggest a potential role in disease pathogenesis and risk assessment. The dysregulation of miRNA-21 and miRNA-27b in OLP underscores their potential as salivary biomarkers for diagnosis and disease monitoring. Moreover, the non-invasive nature of salivary miRNAs offers promising clinical applications, enhancing early detection and personalized management strategies for OLP.
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    Spatio-temporal expression patterns of microRNAs in remodelling and repair of the infarcted heart
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Chiarella-Redfern, H.H.; Rayner, K.J.; Suuronen, E.J.
    MicroRNAs (miRNAs) are small, nonmessenger RNAs, 20-22 nucleotides in size, which regulate gene expression at the post-transcriptional level. Typically, miRNAs target the 3’ untranslated region (3'UTR) of mRNA transcripts leading to mRNA degradation or translational repression. The known dysregulation of miRNAs during cardiac ischemia and the crucial role of miRNA-dependent regulation of angiogenesis, fibrosis and hypertrophy present interesting therapeutic opportunities for repairing and regenerating the heart after myocardial infarction (MI). An understanding of the expression pattern and localization of deleterious and beneficial miRNAs during cardiac ischemia is necessary for the development of therapeutics designed to specifically treat the affected tissue and cell populations. This review focuses on the role and localization of key miRNAs implicated in MI while highlighting how their manipulation may promote cardiac repair.
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    The roles and clinical significance of microRNAs in cervical cancer
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wang, Fenfen; Li, Baohua; Xie, Xing
    Cervical carcinogenesis induced by persistent human papillomavirus (HPV) infection represents a stepwise progression from precursors to invasive cervical cancer. Accumulated evidence has shown aberrant expression of microRNAs (miRNAs) in cervical cancer tissues and cells. Further studies reveal that miRNAs play key roles in the initiation and progression of cervical cancer, via specific signaling pathways, including E6-p53, E7-pRb, phosphoinositide3 kinase (PI3K)-Akt, Notch, Wnt/β-catenin, and Hedgehog pathways. Some studies demonstrate that miRNAs might serve as biomarkers or therapeutic targets, presenting a potential prospect in clinical practice. All results provide new insights into the function of miRNAs and the pathogenesis of cervical cancer induced by viral oncoproteins. New approaches for miRNA-based prevention and management for cervical cancer will be developed in the future.

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