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1.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34571538

RESUMO

MicroRNAs (miRNAs) as small 19- to 24-nucleotide noncoding RNAs regulate several mRNA targets and signaling pathways. Therefore, miRNAs are considered key regulators in cellular pathways as well as various pathologies. There is substantial interest in the relationship between disease and miRNAs, which made that one of the important research topics. Interestingly, miRNAs emerged as an attractive approach for clinical application, not only as biomarkers for diagnosis and prognosis or in the prediction of therapy response but also as therapeutic tools. For these purposes, the identification of crucial miRNAs in disease is very important. Databases provided valuable experimental and computational miRNAs-disease information in an accessible and comprehensive manner, such as miRNA target genes, miRNA related in signaling pathways and miRNA involvement in various diseases. In this review, we summarized miRNAs-disease databases in two main categories based on the general or specific diseases. In these databases, researchers could search diseases to identify critical miRNAs and developed that for clinical applications. In another way, by searching particular miRNAs, they could recognize in which disease these miRNAs would be dysregulated. Despite the significant development that has been done in these databases, there are still some limitations, such as not being updated and not providing uniform and detailed information that should be resolved in future databases. This survey can be helpful as a comprehensive reference for choosing a suitable database by researchers and as a guideline for comparing the features and limitations of the database by developer or designer. Short abstract We summarized miRNAs-disease databases that researchers could search disease to identify critical miRNAs and developed that for clinical applications. This survey can help choose a suitable database for researchers.


Assuntos
MicroRNAs , Biologia Computacional , Bases de Dados Factuais , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , Transdução de Sinais
2.
Mol Biol Rep ; 50(7): 6063-6074, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37294470

RESUMO

BACKGROUND: One of the problems with radiation therapy (RT) is that prostate tumor cells are often radio-resistant, which results in treatment failure. This study aimed to determine the procedure involved in radio-resistant prostate cancer apoptosis. For a deeper insight, we devoted a novel bioinformatics approach to analyze the targeting between microRNAs and radio-resistant prostate cancer genes. METHOD: This study uses the Tarbase, and the Mirtarbase databases as validated experimental databases and mirDIP as a predicted database to identify microRNAs that target radio-resistant anti-apoptotic genes. These genes are used to construct the radio-resistant prostate cancer genes network using the online tool STRING. The validation of causing apoptosis by using microRNA was confirmed with flow cytometry of Annexin V. RESULTS: The anti-apoptotic gene of radio-resistant prostate cancer included BCL-2, MCL1, XIAP, STAT3, NOTCH1, REL, REL B, BIRC3, and AKT1 genes. These genes were identified as anti-apoptotic genes for radio-resistant prostate cancer. The crucial microRNA that knockdown all of these genes was hsa-miR-7-5p. The highest rate of apoptotic cells in a cell transfected with hsa-miR-7-5p was (32.90 ± 1.49), plenti III (21.99 ± 3.72), and the control group (5.08 ± 0.88) in 0 Gy (P < 0.001); also, this rate was in miR-7-5p (47.01 ± 2.48), plenti III (33.79 ± 3.40), and the control group (16.98 ± 3.11) (P < 0.001) for 4 Gy. CONCLUSION: The use of this new treatment such as gene therapy to suppress genes involved in apoptosis can help to improve the treatment results and increase the quality of life of patients with prostate cancer.


Assuntos
MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , Qualidade de Vida , Linhagem Celular Tumoral , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Apoptose/genética , Regulação Neoplásica da Expressão Gênica/genética
3.
Mol Biol Rep ; 50(2): 1281-1291, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36451000

RESUMO

BACKGROUND: Bone tissue as a dynamic tissue is able to repair its minor injuries, however, sometimes the repair cannot be completed by itself due to the size of lesion. In such cases, the best treatment could be bone tissue engineering. The use of stem cells in skeletal disorders to repair bone defects has created bright prospects. On the other hand, changes in the expression level of microRNAs (miRs) can lead to the commitment of mesenchymal stem cells (MSCs) to cell lineage. Many studies reported that post-transcriptional regulations by miRNAs are involved in all stages of osteoblast differentiation. METHOD: After the preparing adipose tissue-derived mesenchymal stem cells, the target cells from the third passage were cultured in two groups, transfected MSCs with miR-27a-3p (DM.C + P) and control group. In different times, 7 and 14 days after culture, differentiation of these cells into osteoblast were measured using various techniques including the ALP test and calcium content test, Alizarin Red staining, Immunocytochemistry technique (ICC). Also, the relative expression of bone differentiation marker genes including Osteonectin (ON), Osteocalcin (OC), RUNX Family Transcription Factor 2 (RUNX2), Collagen type I alpha 1 (COL1) was investigated by real-time RT PCR. RESULTS: In comparison with control groups, overexpression of miR-27a-3p in transfected cells resulted in a significant increase in the expression of bone markers genes (ON, OC, RUNX2, COL1), alkaline phosphatase (ALP) activity, and calcium content (p < 0.05). In addition, the results obtained from ICC technique showed that osteocalcin protein is expressed at the surface of bone cells. Furthermore, the expression of APC, as a target of miR-27a-3p, decreased in transfected cells. CONCLUSION: Our data suggest that miR-27a-3p may positively regulates adipose tissue-derived mesenchymal stem cell differentiation into bone by targeting APC and activating the Wnt/b-catenin pathway.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Humanos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Cálcio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular/genética , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Tecido Adiposo/metabolismo , Células Cultivadas
4.
Cell Biochem Funct ; 41(8): 1488-1502, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38014635

RESUMO

Colorectal cancer (CRC) is responsible for a significant number of cancer-related fatalities worldwide. Researchers are investigating the therapeutic potential of ferroptosis, a type of iron-dependent controlled cell death, in the context of CRC. Curcumin, a natural compound found in turmeric, exhibits anticancer properties. This study explores the effects of curcumin on genes related to ferroptosis (FRGs) in CRC. To gather CRC data, we used the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases, while FRGs were obtained from the FerrDb database and PubMed. We identified 739 CRC differentially expressed genes (DEGs) in CRC and discovered 39 genes that were common genes between FRGs and CRC DEGs. The DEGs related to ferroptosis were enriched with various biological processes and molecular functions, including the regulation of signal transduction and glucose metabolism. Using the Drug Gene Interaction Database (DGIdb), we predicted drugs targeting CRC-DEGs and identified 17 potential drug targets. Additionally, we identified eight essential proteins related to ferroptosis in CRC, including MYC, IL1B, and SLC1A5. Survival analysis revealed that alterations in gene expression of CDC25A, DDR2, FABP4, IL1B, SNCA, and TFAM were associated with prognosis in CRC patients. In SW480 human CRC cells, treatment with curcumin decreased the expression of MYC, IL1B, and EZH2 mRNA, while simultaneously increasing the expression of SLCA5 and CAV1. The findings of this study suggest that curcumin could regulate FRGs in CRC and have the potential to be utilized as a therapeutic agent for treating CRC.


Assuntos
Neoplasias Colorretais , Curcumina , Ferroptose , Humanos , Curcumina/farmacologia , Morte Celular , Curcuma , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Antígenos de Histocompatibilidade Menor , Sistema ASC de Transporte de Aminoácidos
5.
Mikrochim Acta ; 190(12): 482, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-37999813

RESUMO

A poly(n-butyl acrylate)-gold-MXene quantum dots (PBA-Au-MXene QD) nanocomposite-based biosensor is presented that is modified by unique antisense single-stranded DNA (ssDNA) and uses the electrochemical detection methods of DPV, CV, and EIS to early detect miR-122 as a breast cancer biomarker in real clinical samples. This fabrication method is based on advanced nanotechnology, at which a poly(n-butyl acrylate) (PBA) as a non-conductive polymer transforms into a conductive composite by incorporating Au-MXene QD. This biosensor had a limit of detection (LOD) of 0.8 zM and a linear range from 0.001 aM to 1000 nM, making it capable of detecting the low concentrations of miR-122 in patient samples. Moreover, it allows approximately 100% sensitivity and 100% specificity for miR-122 without extraction. The synthesis and detection characteristics were evaluated by different complementary tests such as AFM, FTIR, TEM, and FESEM. This new biosensor can have a high potential in clinical applications to detect breast cancer early and hence improve patient outcomes.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Técnicas Biossensoriais/métodos
6.
Andrologia ; 54(9): e14497, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35700742

RESUMO

The inadequate efficacy of the current treatments for metastatic prostate cancer has directed efforts to the discovery of novel therapies. MicroRNAs (miRNAs) have been considered potential therapeutic agents due to their ability to control gene expression and cellular pathways. The accurate identification of genes and pathways which are targeted by a miRNA is the first step in the therapeutic use of these molecules. In this regard, there are multiple experimental and computational methods to predict and confirm the miRNA-mRNA relationships. The targeting the androgen receptor (AR) indirectly as the most important mediator of prostate cancer has been posited to both control the disease and prevent resistance to treatment. This study aimed to identify miRNAs targeting AR coregulators. For this purpose, we examined target genes by combining miRNA-mRNA computational and experimental data from various databases. miR-27a-3p and miR-124 displayed the highest scores and were selected as miRNAs with the potential to target candidate genes. Next, three cell lines of prostate cancer including PC3, LNCAP, and DU145 were transfected with plasmids which were expressed these selected miRNAs. Then, the gene expression and cell cycle analysis were performed. A decrease was observed in cell viability in all three cell lines than the cells transfected with backbone plasmid. Furthermore, the findings indicated that miR-27a-3p and miR-124 led to a significant decrease in the expression of all genes that were studied in PC3 cell line. In addition, miR-124 caused significant the cellular arrest in the G0/G1 stage, while for miR-27a-3p, this arrest occurred was in the G2/M stage. Our results indicated that the function of a unique miRNA could be different in different cell lines with particular cancer phenotype based on the cell line stage. These findings offer the possibility of employing the miR-124 and miR-27a-3p as therapeutic agents for prostate cancer treatment.


Assuntos
MicroRNAs , Neoplasias da Próstata , Linhagem Celular Tumoral , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Mensageiro , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
7.
Anal Biochem ; 633: 114406, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34619101

RESUMO

MicroRNAs (miRNAs) are short RNA sequences found in eukaryotic cells and they are involved in several diseases pathogenesis including different types of cancers, metabolic and cardiovascular disorders. Thus, miRNAs circulating in serum, plasma, and other body fluids are employed as biomarkers for diagnostic and prognostic purposes and in assessment of drug response. Thus, various methods have been developed for detection of miRNAs including northern blotting, reverse transcriptase polymerase chain reaction (RT-PCR), next-generation sequencing, microarray, and isothermal amplification that are recognized as traditional methods. Considering the importance of early diagnosis and treatment of miRNAs-related diseases, development of simple, one-step, sensitive methods is of great interest. Nowadays developing technologies including lateral flow assay, biosensors (optical and electrochemical) and microfluidic systems which are simple fast responding, user-friendly, and are enabled with visible detection have gained considerable attention. This review briefly discusses miRNAs detection' methods, with a particular focus on lateral flow assay, biosensors, and microfluidic systems as novel and practical procedures.


Assuntos
Técnicas Biossensoriais , MicroRNA Circulante/análise , Técnicas Eletroquímicas , Técnicas Analíticas Microfluídicas , MicroRNA Circulante/genética , Humanos , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Phytother Res ; 35(10): 5596-5622, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34390063

RESUMO

Inflammation is the main contributing factor to atheroma formation in atherosclerosis. Interleukin-1 beta (IL-1ß) is an inflammatory mediator found in endothelial cells and resident leukocytes. Canakinumab is a selective monoclonal antibody against IL-1ß which attenuates inflammation and concurrently precipitates fatal infections and sepsis. Natural products derived from medicinal plants, herbal remedy and functional foods are widely used nowadays. Experimental and clinical trial evidence supports that some natural products such as curcumin, resveratrol, and quercetin have potential effects on IL-1ß suppression. In this review, we tried to document findings that used medicinal plants and plant-based natural products for treating atherosclerosis and its related diseases through the suppression of IL-1ß.


Assuntos
Aterosclerose , Produtos Biológicos , Doenças Cardiovasculares , Anticorpos Monoclonais , Aterosclerose/tratamento farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Células Endoteliais , Humanos , Interleucina-1beta
9.
Int J Mol Sci ; 22(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922585

RESUMO

Cardiovascular diseases (CVDs) have been classified into several types of disease, of which atherosclerosis is the most prevalent. Atherosclerosis is characterized as an inflammatory chronic disease which is caused by the formation of lesions in the arterial wall. Subsequently, lesion progression and disruption ultimately lead to heart disease and stroke. The development of atherosclerosis is the underlying cause of approximately 50% of all deaths in westernized societies. Countless studies have aimed to improve therapeutic approaches for atherosclerosis treatment; however, it remains high on the global list of challenges toward healthy and long lives. Some patients with familial hypercholesterolemia could not get intended LDL-C goals even with high doses of traditional therapies such as statins, with many of them being unable to tolerate statins because of the harsh side effects. Furthermore, even in patients achieving target LDL-C levels, the residual risk of traditional therapies is still significant thus highlighting the necessity of ongoing research for more effective therapeutic approaches with minimal side effects. Decoy-based drug candidates represent an opportunity to inhibit regulatory pathways that promote atherosclerosis. In this review, the potential roles of decoys in the treatment of atherosclerosis were described based on the in vitro and in vivo findings.


Assuntos
Aterosclerose/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Terapia de Alvo Molecular , Oligodesoxirribonucleotídeos/administração & dosagem , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Humanos
10.
J Cell Physiol ; 235(4): 3222-3234, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31599460

RESUMO

Prostate cancer (PCa) is one of the most common cancers and the fifth most common reason for cancer deaths in the males. Surgical castration combined with androgen deprivation therapy, antiandrogens, and androgen synthesis inhibitors is the current therapeutic modalities for PCa. These strategies inhibit androgen synthesis or reduce its binding to the androgen receptor (AR) but the development of resistance to these therapies and transient responsiveness are challenging issues in the treatment of this cancer. Deregulation of ARs has a vital role in the initiation and progression of PCa. Also, recent findings imply that micro RNAs (miRNAs) are involved in the evolution of PCa and mediate drug resistance in different cancers. Hence, discovering and targeting miRNAs might represent a novel therapeutic approach. This review paid particular attention to the AR pathway and existing information on the possible roles of miRNAs associated with AR pathway and drug resistance to two second-generation antiandrogens, that is, enzalutamide and abiraterone.


Assuntos
MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/genética , Antagonistas de Androgênios/uso terapêutico , Androstenos/uso terapêutico , Benzamidas , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Nitrilas , Feniltioidantoína/análogos & derivados , Feniltioidantoína/uso terapêutico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologia
11.
J Cell Physiol ; 235(2): 966-978, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31347171

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the dominant histological type of esophageal cancer significantly reported in developing nations. There is an increasing evidence suggesting that single nucleotide polymorphisms (SNPs) in the untranslated regions of genes (3'-UTRs) targeted by microRNAs (miRNAs) can change the target gene's expression and thereby affect the individual's cancer risk. Thus, in support of the role of SNPs occurring in miRNA target sites (miR-TS-SNPs) in the cancer, we analyzed the next generation sequencing data of 10 ESCC patients. In each patient, about 3,000 SNPs in 3'-UTRs were obtained in their whole-exome sequencing profiles. We applied two separate methods, manual and computational in silico approaches, to predict the miR-TS-SNPs with more effects on the miRNA-target interactions. dbSNP, 1000G, ExAC, Iranome, miRandb, miRCancer, TargetScan, Human, miRNASNP2 and miRBase databases were used for positive selection of miR-TS-SNPs and DIANA-miRPath v3.0 for pathway analysis. We identified six rare germline miR-TS-SNPs and two other ones with unknown miR-TS-SNPs. We interestingly observed all of these variants in only one patient, which can be evidence of the relationship between miR-TS-SNPs and cancer incidence. The study of cancer genetics including miR-TS-SNPs reveals miRNAs and their related pathways, which will be greatly useful in cancer research from noninvasive biomarkers to new treatments.


Assuntos
Carcinoma de Células Escamosas/genética , Simulação por Computador , Neoplasias Esofágicas/genética , MicroRNAs/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Idoso , Família , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Transcriptoma
12.
Brief Bioinform ; 19(2): 254-262, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28049134

RESUMO

Recent discovery of thousands of small and large noncoding RNAs, in parallel to technical improvements enabling scientists to study the transcriptome in much higher depth, has resulted in massive data generation. This burst of information prompts the development of easily accessible resources for storage, retrieval and analysis of raw and processed data, and hundreds of Web-based tools dedicated to these tasks have been made available. However, the increasing number and diversity of bioinformatics tools, each covering a specific and specialized area, as well as their redundancies, represent potential sources of complication for end users. To overcome these issues, we are introducing an easy-to-follow classification of microRNA (miRNA)-related bioinformatics tools for biologists interested in studying this important class of small noncoding RNAs. We also developed our miRNA database miRNA algorithmic network database (miRandb) that is a meta-database, which presents a survey of > 180 Web-based miRNA databases. These include miRNA sequence, discovery, target prediction, target validation, expression and regulation, functions and their roles in diseases, interactions in cellular pathways and networks and deep sequencing. miRandb recapitulates the diverse possibilities and facilitates that access to the different categories of miRNA resources. Researchers can easily select the category of miRNA information and desired organism, in result eligible databases with their features are presented. This database introducing an easy-to-follow classification of available resources that can facilitate selection of appropriate resources for miRNA-related bioinformatics tools. Finally, we described current shortages and future necessities that assist researchers to use these tools easily. Our database is accessible at http://mirandb.ir.


Assuntos
Biologia Computacional/métodos , MicroRNAs/genética , Sistemas On-Line , Software , Bases de Dados Factuais , Humanos
13.
J Cell Physiol ; 234(3): 2306-2316, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30191973

RESUMO

Colorectal cancer (CRC) is one of the most common cancers globally. Despite recent advances in therapeutic approaches, this cancer continues to have a poor prognosis, particularly when diagnosed late. 5-Fluorouracil (5-FU) has been commonly prescribed for patients with CRC, but resistance to 5-FU is one of the main reasons for failure in the treatment of this condition. Recently, microRNAs (miRNAs) have been established as a means of modifying the signaling pathways involved in initiation and progression of CRC and their role as oncogene or tumor suppressor have been investigated in various studies. Moreover, miRNAs through various mechanisms play an important role in inducing tumor resistance or sensitivity to anticancer drugs. Detecting and targeting these mechanisms may be a new therapeutic approach. This review summarizes the current knowledge about the potential roles of miRNAs in 5-FU resistance, with particular emphasis on molecular mechanism involved.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/uso terapêutico , MicroRNAs/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fluoruracila/efeitos adversos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos
14.
IUBMB Life ; 71(10): 1428-1441, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31322820

RESUMO

Colorectal cancer (CRC) is one of the most common malignancies with poor prognosis. Oxaliplatin-based chemotherapy is an important treatment for CRC; however, the cells develop resistance to therapy. The mechanisms underlying oxaliplatin resistance are complex and unclear. There is increasing evidence that microRNAs (miRNAs) (i.e., miR-34a, miR-143, miR-153, miR-27a, miR-218, and miR-520) play an essential role in tumorigenesis and chemotherapy resistance, by targeting various cellular and molecular pathways (i.e., PI3K/Akt/Wnt, EMT, p53, p21, and ATM) that are involved in the pathogenesis of CRC. Identifying the miRNAs that are involved in chemo-resistance, and their function, may help as a potential therapeutic option for treatment of CRC or as potential prognostic biomarker. Here, we summarized the clinical impact of miRNAs that have critical roles in the development of resistance to oxaliplatin in CRC.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs/genética , Terapia de Alvo Molecular , Oxaliplatina/uso terapêutico , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/terapia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Prognóstico
15.
Adv Exp Med Biol ; 1087: 35-38, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30259355

RESUMO

circRNAs are a novel class of ncRNAs that unlike other ncRNAs are not linear and have a circular structure. These valuable ncRNAs have been detected in a wide range of organisms from plants to animals and in all cell lines and tissues. Commonly, circRNAs have several functions as gene expression regulation at transcriptional or posttranscriptional level, miRNA partnership, and splicing intercede. Currently, circRNAs are roughly remarked in a widespread collection of diseases, and circRNAs simply can be recognized in liquid samples for disease detection and progression assessment. Considering these features of circRNAs, these molecules are evolving the impeccable collection of original biomarkers for disease therapy and diagnosis. As the critical role of these molecules in different aspects medicine and biology, circRNAs are considered as key and critical class of ncRNA in the current ncRNA search field. To simplify the assessment of diverse features of circRNAs, several databases have been established such as circBase, CircInteractome, CircNet, Circ2Traits, CircR2Disease, TCSD, and CSCD. In this chapter, we have an overview on these main circRNA databases and introduce key features of each database.


Assuntos
Bases de Dados Genéticas , RNA , Humanos , Internet , Sistemas On-Line , RNA/análise , RNA/genética , RNA Circular , RNA Longo não Codificante/análise , RNA Longo não Codificante/genética , RNA Neoplásico/genética
16.
Tumour Biol ; 36(6): 4203-12, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25604141

RESUMO

The long-lasting inadequacy of existing treatments for prostate cancer has led to increasing efforts for developing novel therapies for this disease. MicroRNAs (miRNAs) are believed to have considerable therapeutic potential due to their role in regulating gene expression and cellular pathways. Identifying miRNAs that efficiently target genes and pathways is a key step in using these molecules for therapeutic purposes. Moreover, computational methods have been devised to help identify candidate miRNAs for each gene/pathway. MAPK and JAK/STAT pathways are known to have essential roles in cell proliferation and neoplastic transformation in different cancers including prostate cancer. Herein, we tried to identify miRNAs that target these pathways in the context of prostate cancer as therapeutic molecules. Genes involved in these pathways were analyzed with various algorithms to identify potentially targeting miRNAs. miR-23a and miR-23b were then selected as the best potential candidates that target a higher number of genes in these pathways with greater predictive scores. We then analyzed the expression of candidate miRNAs in LNCAP and PC3 cell lines as well as prostate cancer clinical samples. miR-23a and miR-23b showed a significant downregulation in cell line and tissue samples, a finding which is consistent with overactivation of these pathways in prostate cancer. In addition, we overexpressed miR-23a and miR-23b in LNCAP and PC3 cell lines, and these two miRNAs decreased IL-6R expression which has a critical role in these pathways. These results suggest the probability of utilizing miR-23a and miR-23b as therapeutic targets for the treatment of prostate cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , MicroRNAs/biossíntese , Neoplasias da Próstata/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinases/genética , Masculino , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Neoplasias da Próstata/patologia , Fatores de Transcrição STAT/genética , Transdução de Sinais/genética
18.
Curr Med Chem ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38874036

RESUMO

INTRODUCTION: microRNA (miRNA) levels are dysregulated in many cancers, suggesting that miRNA-based therapy may be effective. The molecular pathways of colorectal cancer (CRC) development are unknown. METHOD: Understanding miRNAs implicated in CRC formation may reveal new diagnostic and therapeutic targets. Angiogenesis is a key mechanism in tumor growth. CRC treatment may involve inhibiting angiogenesis, but existing drugs can cause negative effects. Tranexamic acid, an FDA-approved medication, may reduce the adverse effects of angiogenesis inhibitors. This work examined miRNAs implicated in CRC angiogenesis and how miR-16 and tranexamic acid may synergistically decrease CRC cell migration and angiogenesis. We identified miRNAs targeting CRC angiogenesis genes using bioinformatic databases. Proteins were docked with tranexamic acid utilizing the PyRx software. Quantitative Real-time PCR was used to analyze the effects of overexpressed miRNA and tranexamic acid on the expression of target genes. Scratch, transwell migration, and Chicken Chorioallantoic Membrane (CAM) assays were used to evaluate the effect of selected miRNA and tranexamic acid on the invasion and angiogenesis of CRC cells. in silico studies identified hsa-miR-16-5p, -101-3p, and 34a-5p as possible CRC angiogenesis modulators. RESULTS: The study found that miR-16 and tranexamic acid influence the expression of VEGFA, ANGPT2, MMP9, and HIF1A. miR-16 and tranexamic acid influenced CRC cell movement in scratch tests and transwell migration assays. Furthermore, the CAM assay results demonstrated that miR-16 and tranexamic acid can alter angiogenesis in CRC. CONCLUSION: These findings highlight the potential of miR-16 and tranexamic acid as combination therapeutic agents for CRC, with the ability to simultaneously target tumorigenesis and angiogenesis.

19.
Clin Exp Dent Res ; 10(2): e877, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38481355

RESUMO

OBJECTIVES: Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. MATERIALS AND METHODS: In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson's χ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. RESULTS: Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2  test showed a statistically significant difference in miR-3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group. CONCLUSIONS: The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Líquen Plano Bucal , MicroRNAs , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Líquen Plano Bucal/diagnóstico , Líquen Plano Bucal/genética , Estudos Transversais , Regulação para Baixo , Biomarcadores/análise , MicroRNAs/genética
20.
Curr Pharm Des ; 30(4): 310-322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38310566

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression. METHODS: GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients. RESULTS: The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p's engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes. CONCLUSION: This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches.


Assuntos
Biomarcadores Tumorais , Líquen Plano Bucal , MicroRNAs , Neoplasias Bucais , Humanos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Simulação por Computador , Regulação Neoplásica da Expressão Gênica , Líquen Plano Bucal/genética , Líquen Plano Bucal/sangue , Líquen Plano Bucal/diagnóstico , MicroRNAs/sangue , MicroRNAs/genética , Neoplasias Bucais/genética , Neoplasias Bucais/sangue , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Prognóstico
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