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1.
Cancer Metastasis Rev ; 42(3): 725-740, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37490255

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with poor prognosis due to early metastasis, low diagnostic rates at early stages, and resistance to current therapeutic regimens. Despite numerous studies and clinical trials, the mortality rate for PDAC has shown limited improvement. Therefore, there is a pressing need to attain. a more comprehensive molecular characterization to identify biomarkers enabling early detection and evaluation of treatment response. MicroRNA (miRNAs) are critical regulators of gene expression on the post-transcriptional level, and seem particularly interesting as biomarkers due to their relative stability, and the ability to detect them in fixed tissue specimens and biofluids. Deregulation of miRNAs is common and affects several hallmarks of cancer and contribute to the oncogenesis and metastasis of PDAC. Unique combinations of upregulated oncogenic miRNAs (oncomiRs) and downregulated tumor suppressor miRNAs (TsmiRs), promote metastasis, characterize the tumor and interfere with chemosensitivity of PDAC cells. Here, we review several oncomiRs and TsmiRs involved in chemoresistance to gemcitabine and FOLFIRINOX in PDAC and highlighted successful/effective miRNA-based therapy approaches in vivo. Integrating miRNAs in PDAC treatment represents a promising therapeutic avenue that can be used as guidance for personalized medicine for PDAC patients.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas
2.
Int J Mol Sci ; 21(13)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610582

RESUMO

Extracellular vesicles (EVs) receive special attention from oncologists due to their assumed usefulness as prognostic markers, vaccines to induce anti-cancer immune response, and physiological delivery tools. The latter application, which supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell, which may have an advantage over in vitro procedures, since some of them significantly influence EVs' properties. Otherwise, our research findings suggest that EVs could be passively supplemented with micro RNAs (miRNAs) or miRNA antagonists to induce expected biological effect. Furthermore, our observations imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. Finally, the route of EVs' administration also determines their bioavailability and eventually induced therapeutic effect. Besides, EV membrane lipids may possibly possess immune adjuvant activity. The review summarizes the current knowledge on the possibilities to manipulate EVs to use them as a delivery tool, with the special emphasis on anti-cancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Vesículas Extracelulares/fisiologia , Neoplasias/terapia , Transporte Biológico , Exossomos/metabolismo , Exossomos/fisiologia , Vesículas Extracelulares/metabolismo , Humanos , Imunidade/fisiologia , MicroRNAs/metabolismo , MicroRNAs/farmacologia , Neoplasias/metabolismo
3.
Int J Mol Sci ; 19(1)2017 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-29295562

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. They play a key role in several biological processes. Their abnormal expression may lead to malignant cell transformation. This study aimed to evaluate the expression profile of 84 miRNAs involved in tumorigenesis in immortalized cells of myometrium (MM), uterine leiomyoma (ULM), and uterine leiomyosarcoma (ULMS). Specific cell lines were cultured and qRT-PCR was performed. Thirteen miRNAs presented different expression profiles in ULM and the same thirteen in ULMS compared to MM. Eight miRNAs were overexpressed, and five were underexpressed in ULM. In ULMS cells, five miRNAs exhibited an overexpression and eight were down-regulated. Six miRNAs (miR-1-3p, miR-130b-3p, miR-140-5p, miR-202-3p, miR-205-5p, and miR-7-5p) presented a similar expression pattern in cell lines compared to patient samples. Of these, only three miRNAs showed significant expression in ULM (miR-1-3p, miR-140-5p, and miR-7-5p) and ULMS (miR-1-3p, miR-202-3p, and miR-7-5p). Our preliminary approach identified 24 oncomirs with an altered expression profile in ULM and ULMS cells. We identified four differentially expressed miRNAs with the same profile when compared with patients' samples, which strongly interacted with relevant genes, including apoptosis regulator (BCL2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), insulin like growth factor 1 receptor (IGF1R),serine/threonine kinase (RAF1), receptor tyrosine kinase (MET), and bHLH transcription factor (MYCN). This led to alterations in their mRNA-target.


Assuntos
Perfilação da Expressão Gênica , Leiomiossarcoma/genética , MicroRNAs/genética , Neoplasias Uterinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Análise por Conglomerados , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade
4.
Yale J Biol Med ; 90(4): 583-598, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29259523

RESUMO

Since their invention in 1991, peptide nucleic acids (PNAs) have been used in a myriad of chemical and biological assays. More recently, peptide nucleic acids have also been demonstrated to hold great potential as therapeutic agents because of their physiological stability, affinity for target nucleic acids, and versatility. While recent modifications in their design have further improved their potency, their preclinical development has reached new heights due to their combination with recent advancements in drug delivery. This review focuses on recent advances in PNA therapeutic applications, in which chemical modifications are made to improve PNA function and nanoparticles are used to enhance PNA delivery.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Ácidos Nucleicos Peptídicos/administração & dosagem , Ácidos Nucleicos Peptídicos/uso terapêutico , Elementos Antissenso (Genética) , Estabilidade de Medicamentos , Edição de Genes , Humanos , MicroRNAs , Estrutura Molecular , Nanopartículas/administração & dosagem , Nanopartículas/química , Ácidos Nucleicos Peptídicos/química , Ácidos Nucleicos Peptídicos/farmacocinética , Solubilidade
5.
Tumour Biol ; 37(11): 14463-14477, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27644253

RESUMO

Breast cancer is a malignant disease to treat among female worldwide due to its high capability to metastasize and mutate. Epithelial-mesenchymal transition is one of the essential processes involved in the metastatic capacity of breast cancer. In the recent time, the studies demonstrate that microRNAs, a kind of small non-coding RNA molecules, could be served as negative regulators in breast cancer, regulating cell cycle, drug resistance, and the process of metastasis in cancer development. With the assistance of microRNA profiling, the study concentrating on the regulatory function of miRNAs in breast cancer could be investigated more effectively and efficiently. More recent studies demonstrate that miRNAs have an important role to play in the EMT process of breast cancer to modulate metastasis. This small essay is on the purpose of demonstrating the significance and detection of miRNAs in breast cancer EMT process as oncogenes and tumor suppress genes through miRNA profiling according to the reports mainly in the recent 5 years, providing the evidence of efficient target therapy and effective pro-diagnosis focusing on miRNAs expression of breast cancer patients.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Metástase Neoplásica/genética
6.
Pathol Res Pract ; 253: 154995, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113765

RESUMO

Breast cancer (BC) is the most prevalent aggressive malignant tumor in women worldwide and develops from breast tissue. Although cutting-edge treatment methods have been used and current mortality rates have decreased, BC control is still not satisfactory. Clarifying the underlying molecular mechanisms will help clinical options. Extracellular vesicles known as exosomes mediate cellular communication by delivering a variety of biomolecules, including proteins, oncogenes, oncomiRs, and even pharmacological substances. These transferable bioactive molecules can alter the transcriptome of target cells and affect signaling pathways that are related to tumors. Numerous studies have linked exosomes to BC biology, including therapeutic resistance and the local microenvironment. Exosomes' roles in tumor treatment resistance, invasion, and BC metastasis are the main topics of discussion in this review.


Assuntos
Neoplasias da Mama , Exossomos , Vesículas Extracelulares , Feminino , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Exossomos/metabolismo , Transdução de Sinais , Comunicação Celular , Vesículas Extracelulares/metabolismo , Microambiente Tumoral
7.
Microrna ; 13(1): 33-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38284737

RESUMO

INTRODUCTION: To retrieve, and classify PCa miRNAs and identify the functional relationship between miRNAs and their targets through literature collection with computational analysis. BACKGROUND: MicroRNAs play a role in gene regulation, which can either repress or activate the gene. Hence, the functions of miRNAs are dependent on the target gene. This study will be the first of its kind to combine computational analysis with corpus PCa data. Effectively, our study reported the huge number of miRNAs associated with PCa along with functional information. OBJECTIVE: The identification and classification of previously known full PCa miRNAs and their targets were made possible by mining the literature data. Systems Biology and curated data mining assisted in identifying optimum miRNAs and their target genes for PCa therapy. METHODS: PubMed database was used to collect the PCa literature up to December 2021. Pubmed. mineR package was used to extract the microRNAs associated articles and manual curation was performed to classify the microRNAs based on the function in PCa. PPI was constructed using the STRING database. Pathway analysis was performed using PANTHER and ToppGene Suite Software. Functional analysis was performed using ShinyGO software. Cluster analysis was performed using MCODE 2.0, and Hub gene analysis was performed using cytoHubba. The genemiRNA network was reconstructed using Cytoscape. RESULTS: Unique PCa miRNAs were retrieved and classified from mined PCa literature. Six hundred and five unique miRNAs from 250 articles were considered as oncomiRs to trigger PCa. One hundred and twenty unique miRNAs from 118 articles were considered Tumor Suppressor miRNAs to suppress the PCa. Twenty-four unique miRNAs from 22 articles were utilized as treatment miRNAs to treat PCa. miRNAs target genes and their significant pathways, functions and hub genes were identified. CONCLUSION: miR-27a, miR-34b, miR-495, miR-23b, miR-100, miR-218, Let-7a family, miR-27a- 5p, miR-34c, miR-34a, miR-143/-145, miR-125b, miR-124 and miR-205 with their target genes AKT1, SRC, CTNNB1, HRAS, MYC and TP53 are significant PCa targets.


Assuntos
Biologia Computacional , Redes Reguladoras de Genes , MicroRNAs , MicroRNAs/genética , Humanos , Biologia Computacional/métodos , Redes Reguladoras de Genes/genética , Mineração de Dados/métodos , Regulação Neoplásica da Expressão Gênica/genética , Mapas de Interação de Proteínas/genética
8.
Biomed Pharmacother ; 171: 116165, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237348

RESUMO

Cancer development is a complex process that primarily results from the combination of genetic alterations and the dysregulation of major signalling pathways due to interference with the epigenetic machinery. As major epigenetic regulators, miRNAs are central players in the control of many key tumour development factors. These miRNAs have been classified as oncogenic miRNAs (oncomiRs) when they target tumour suppressor genes and tumour suppressor miRNAs (TS miRNAs) when they inhibit oncogene protein expression. Most of the mechanisms that modulate oncomiR expression are linked to transcriptional or posttranscriptional regulation. However, non-transcriptional processes, such as gene amplification, have been described as alternative processes that are responsible for increasing oncomiR expression. The current review summarises the different mechanisms controlling the upregulation of oncomiR expression in cancer cells and the tumour microenvironment (TME). Detailed knowledge of the mechanism underlying the regulation of oncomiR expression in cancer may pave the way for understanding the critical role of oncomiRs in cancer development and progression.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , Neoplasias/metabolismo , Genes Supressores de Tumor , Oncogenes , Proteínas Oncogênicas/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral
9.
Oncol Res ; 32(6): 1011-1019, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827323

RESUMO

This review aimed to describe the inculpation of microRNAs (miRNAs) in thyroid cancer (TC) and its subtypes, mainly medullary thyroid carcinoma (MTC), and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC. Additionally, the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed. This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes, mainly MTC. Additionally, web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described. MiRNAs can perform as oncomiRs or antioncoges, relying on the target mRNAs they regulate. MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases, particularly in cancer. MiRNAs are involved in the modulation of fundamental pathways related to cancer, resembling cell cycle checkpoints and DNA repair pathways. MiRNAs are also rather stable and can reliably be detected in different types of biological materials, rendering them favorable diagnosis and prognosis biomarkers as well. MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets. The contribution of miRNAs in thyroid cancer, particularly MTC, is an active area of research, and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.


Assuntos
Biomarcadores Tumorais , Carcinoma Neuroendócrino , Biologia Computacional , MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/patologia , MicroRNAs/genética , Biomarcadores Tumorais/genética , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/diagnóstico , Prognóstico , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Internet , Terapia de Alvo Molecular
10.
Curr Stem Cell Res Ther ; 19(11): 1525-1534, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38265389

RESUMO

BACKGROUND: MSCs are a part of the tumor microenvironment, which secrete cytokines and chemokines. They can affect metastasis and the growth of tumors. metastamiRs are newly recognized regulatory elements of the metastasis pathway which are involved in epithelial-to-mesenchymal transition (EMT). OBJECTIVE: In the present study, we aimed to assess the expression profile of metastamiRs in the context of MSCs in correlation with their invasion and migration power. METHODS: Tumor-isolated BC-MSCs and normal human mammary epithelial cells (HMECs) along with MCF-7, MDA-MB231, and MCF-10A cells were prepared and confirmed for their identity. The cells were assessed for CD44+CD24¯ percentage, Oct-4, and Survivin expression. GEO, KEGG, and TCGA databases were investigated to detect differential miR-expressions. Real- time PCR for 13 miRs was performed using LNA primers. Ultimately, Transwell-Matrigel assays as used to assess the level of migration and invasion. RESULTS: Our results indicated that some oncomiRs like miR-10b were upregulated in BC-MSCs, while the levels of miR-373 and miR-520c were similar to the MCF-10A. Generally, miR-200 family members were on lower levels compared to the other miR-suppressor (miR-146a, 146b, and 335). miR-31 and 193b were up-regulated in MCF-10A. The most invasiveness was observed in the MDA-MB231 cell line. CONCLUSION: We have demonstrated that the miR-expression levels of BC-MSCs are somewhat in between MCF-7 and MDA-MB231 miR-expression levels. This could be the logic behind the moderate level of invasion in BC-MSCs. Therefore, miR-therapy approaches such as miR-mimic or antagomiRs could be used for BC-MSCs in clinical cancer therapy.


Assuntos
Neoplasias da Mama , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Células-Tronco Mesenquimais/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Células MCF-7 , Linhagem Celular Tumoral , Microambiente Tumoral/genética
11.
Int Rev Cell Mol Biol ; 386: 133-165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38782498

RESUMO

MicroRNAs (miRNAs) are increasingly recognized as central players in the regulation of eukaryotic physiological processes. These small double stranded RNA molecules have emerged as pivotal regulators in the intricate network of cellular signaling pathways, playing significant roles in the development and progression of human cancers. The central theme in miRNA-mediated regulation of signaling pathways involves their ability to target and modulate the expression of pathway components. Aberrant expression of miRNAs can either promote or suppress key signaling events, influencing critical cellular processes such as proliferation, apoptosis, angiogenesis, and metastasis. For example, oncogenic miRNAs often promote cancer progression by targeting tumor suppressors or negative regulators of signaling pathways, thereby enhancing pathway activity. Conversely, tumor-suppressive miRNAs frequently inhibit oncogenic signaling by targeting key components within these pathways. This complex regulatory crosstalk underscores the significance of miRNAs as central players in shaping the signaling landscape of cancer cells. Furthermore, the therapeutic implications of targeting miRNAs in cancer are substantial. miRNAs can be manipulated to restore normal signaling pathway activity, offering a potential avenue for precision medicine. The development of miRNA-based therapeutics, including synthetic miRNA mimics and miRNA inhibitors, has shown promise in preclinical and clinical studies. These strategies aim to either enhance the activity of tumor-suppressive miRNAs or inhibit the function of oncogenic miRNAs, thereby restoring balanced signaling and impeding cancer progression. In conclusion, the crosstalk between miRNAs and signaling pathways in human cancers is a dynamic and influential aspect of cancer biology. Understanding this interplay provides valuable insights into cancer development and progression. Harnessing the therapeutic potential of miRNAs as regulators of signaling pathways opens up exciting opportunities for the development of innovative cancer treatments with the potential to improve patient outcomes. In this chapter, we provide an overview of the crosstalk between miRNAs and signaling pathways in the context of cancer and highlight the potential therapeutic implications of targeting this regulatory interplay.


Assuntos
MicroRNAs , Neoplasias , Transdução de Sinais , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Neoplasias/genética , Animais , Regulação Neoplásica da Expressão Gênica
12.
Mol Biotechnol ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38133750

RESUMO

Breast cancer, a prevalent and aggressive malignancy among females worldwide, poses a significant challenge due to resistance to chemotherapy and tyrosine kinase inhibitors. In breast cancer, ABC transporters play a pivotal role by contributing to chemoresistance and drug efflux, a phenomenon observed also in various cancers. This study aims to elucidate the role of oncomiRs miR-15, miR-21, and miR-let-7 in breast cancer etiology and their impact on chemotherapy-resistant oncogenes ABCA1, ABCB1, and ABCC1. Blood samples from female breast cancer patients were analyzed to assess the expression levels of miRNAs and oncogenes by qPCR. Significantly, miR-21 exhibited a positive correlation with ABCA1 in newly diagnosed patients, while miR-15 and miR-let-7 displayed a positive correlation with ABCA1 in the metastasis group. Additionally, miR-let-7 demonstrated a negative correlation with ABCC1 in newly diagnosed patients. This study's findings provide valuable insights into the cancer etiology of these miRNAs and their interactions with ABCA1, ABCB1, and ABCC1. Targeting these interactions holds promise for mitigating drug efflux and chemoresistance in breast cancer, potentially enhancing current treatments and improving patient outcomes.

13.
J Oral Maxillofac Pathol ; 27(2): 364-373, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854932

RESUMO

Oral squamous cell carcinoma (OSCC) ranks sixth among all cancers in the world, affecting various sites of the oral cavity with associated several risk factors. High mortality has been associated with the presence of metastasis during the time of diagnosis and an increase in therapeutic relapses. Micro-RNAs (miRNAs) are a group of small non-coding RNAs with salient roles in the initiation and progression of cancer. The tumorigenesis of OSCC is associated with the dysregulation of several miRNAs. MicroRNAs are an area of recent interest, and numerous studies have been reported and are being undertaken to identify their role in diagnostic and prognostic value for oral cancers. Most of the miRNA processing machinery is considered to be either up-/down-regulated in OSCC, but the underlying mechanism of miRNA dysregulation and their activity as either a tumour suppressor or an oncogene in oral carcinogenesis is not yet clear. The article presents a concise review of the available current literature regarding the various miRNAs' signatures in OSCC and their role as diagnostic/prognostic biomarkers.

14.
Diagnostics (Basel) ; 13(19)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37835815

RESUMO

MicroRNAs (miRNAs) constitute a subclass of non-coding RNAs that exert substantial influence on gene-expression regulation. Their tightly controlled expression plays a pivotal role in various cellular processes, while their dysregulation has been implicated in numerous pathological conditions, including cancer. Among cancers affecting women, breast cancer (BC) is the most prevalent malignant tumor. Extensive investigations have demonstrated distinct expression patterns of miRNAs in normal and malignant breast cells. Consequently, these findings have prompted research efforts towards leveraging miRNAs as diagnostic tools and the development of therapeutic strategies. The aim of this review is to describe the role of miRNAs in BC. We discuss the identification of oncogenic, tumor suppressor and metastatic miRNAs among BC cells, and their impact on tumor progression. We describe the potential of miRNAs as diagnostic and prognostic biomarkers for BC, as well as their role as promising therapeutic targets. Finally, we evaluate the current use of artificial intelligence tools for miRNA analysis and the challenges faced by these new biomedical approaches in its clinical application. The insights presented in this review underscore the promising prospects of utilizing miRNAs as innovative diagnostic, prognostic, and therapeutic tools for the management of BC.

15.
Genes (Basel) ; 14(7)2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37510280

RESUMO

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we comprehensively summarized the importance of miRNA in human and canine cancer research. We discussed the current state of development and potential for the miRNA as both a diagnostic marker and a therapeutic target.


Assuntos
MicroRNAs , Neoplasias , Humanos , Animais , Cães , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica
16.
J Pharm Anal ; 13(11): 1235-1251, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38174117

RESUMO

Colorectal cancer (CRC) is among the leading causes of cancer mortality. The lifetime risk of developing CRC is about 5% in adult males and females. CRC is usually diagnosed at an advanced stage, and at this point therapy has a limited impact on cure rates and long-term survival. Novel and/or improved CRC therapeutic options are needed. The involvement of microRNAs (miRNAs) in cancer development has been reported, and their regulation in many oncogenic pathways suggests their potent tumor suppressor action. Although miRNAs provide a promising therapeutic approach for cancer, challenges such as biodegradation, specificity, stability and toxicity, impede their progression into clinical trials. Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy. The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.

17.
Genes (Basel) ; 14(3)2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36980984

RESUMO

Leiomyomas, also referred to as fibroids, belong to the most common type of benign tumors developing in the myometrium of the uterus. Intravenous leiomyomatosis (IVL) tends to be regarded as a rare type of uterine leiomyoma. IVL tumors are characterized by muscle cell masses developing within the uterine and extrauterine venous system. The underlying mechanism responsible for the proliferation of these lesions is still unknown. The aim of the study was to investigate the expression of the two epigenetic factors, oncomiRs miR-182-5p and miR-103a-3p, in intravenous leiomyomatosis. This study was divided into two stages: initially, miR-182-5p and miR-103a-3p expression was assessed in samples coming from intravenous leiomyomatosis localized in myometrium (group I, n = 6), intravenous leiomyomatosis beyond the uterus (group II; n = 5), and the control group, i.e., intramural leiomyomas (group III; n = 9). The expression level of miR-182-5p was significantly higher in samples coming from intravenous leiomyomatosis (group I and group II) as compared to the control group (p = 0.029 and p = 0.024, respectively). In the second part of the study, the expression levels of the studied oncomiRs were compared between seven samples delivered from one woman during a four-year observation. The long-term follow-up of one patient demonstrated significantly elevated levels of both studied oncomiRs in intravenous leiomyomatosis in comparison to intramural leiomyoma samples.


Assuntos
Leiomiomatose , MicroRNAs , Neoplasias Uterinas , Feminino , Humanos , Leiomiomatose/genética , Leiomiomatose/patologia , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Útero/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
18.
J Pers Med ; 12(9)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36143213

RESUMO

Multiple myeloma (MM) is the second most common hematological malignancy. Despite the huge therapeutic progress thanks to the introduction of novel therapies, MM remains an incurable disease. Extensive research is currently ongoing to find new options. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post-transcriptional level. Aberrant expression of miRNAs in MM is common. Depending on their role in MM development, miRNAs have been reported as oncogenes and tumor suppressors. It was demonstrated that specific miRNA alterations using miRNA mimics or antagomirs can normalize the gene regulatory network and signaling pathways in the microenvironment and MM cells. These properties make miRNAs attractive targets in anti-myeloma therapy. However, only a few miRNA-based drugs have been entered into clinical trials. In this review, we discuss the role of the miRNAs in the pathogenesis of MM, their current status in preclinical/clinical trials, and the mechanisms by which miRNAs can theoretically achieve therapeutic benefit in MM treatment.

19.
Front Immunol ; 13: 913951, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189271

RESUMO

Currently, microRNAs have been established as central players in tumorigenesis, but above all, they have opened an important door for our understanding of immune and tumor cell communication. This dialog is largely due to onco-miR transfer from tumor cells to cells of the tumor microenvironment by exosome. This review outlines recent advances regarding the role of oncomiRs in enhancing cancer and how they modulate the cancer-related immune response in the tumor immune microenvironment. MicroRNAs (miRNAs) are a type of noncoding RNA that are important posttranscriptional regulators of messenger RNA (mRNA) translation into proteins. By regulating gene expression, miRNAs enhance or inhibit cancer development and participate in several cancer biological processes, including proliferation, invasion metastasis, angiogenesis, chemoresistance and immune escape. Consistent with their widespread effects, miRNAs have been categorized as oncogenes (oncomiRs) or tumor suppressor (TS) miRNAs. MiRNAs that promote tumor growth, called oncomiRs, inhibit messenger RNAs of TS genes and are therefore overexpressed in cancer. In contrast, TS miRNAs inhibit oncogene messenger RNAs and are therefore underexpressed in cancer. Endogenous miRNAs regulate different cellular pathways in all cell types. Therefore, they are not only key modulators in cancer cells but also in the cells constituting their microenvironments. Recently, it was shown that miRNAs are also involved in intercellular communication. Indeed, miRNAs can be transferred from one cell type to another where they regulate targeted gene expression. The primary carriers for the transfer of miRNAs from one cell to another are exosomes. Exosomes are currently considered the primary carriers for communication between the tumor and its surrounding stromal cells to support cancer progression and drive immune suppression. Exosome and miRNAs are seen by many as a hope for developing a new class of targeted therapy. This review outlines recent advances in understanding the role of oncomiRs in enhancing cancer and how they promote its aggressive characteristics and deeply discusses the role of oncomiRs in suppressing the anticancer immune response in its microenvironment. Additionally, further understanding the mechanism of oncomiR-related immune suppression will facilitate the use of miRNAs as biomarkers for impaired antitumor immune function, making them ideal immunotherapy targets.


Assuntos
MicroRNAs , Neoplasias , Genes Supressores de Tumor , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/terapia , Oncogenes , RNA Mensageiro , Microambiente Tumoral/genética
20.
Crit Rev Oncol Hematol ; 180: 103850, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36261117

RESUMO

Oral or mouth cancer is the 16th most common form of cancer among the world's topmost malignancies. Healthy lifestyle and control of known risk factors can reduce its incidences further. Patients succumb to oral cancer when diagnosed late and lack timely access to tertiary care. Molecular biomarkers might help in early detection of oral cancer. Recently, researchers have identified numerous microRNAs which play a crucial role in promoting and suppressing oral cancers. miRNAs are short non-coding RNA molecules (18-22 nucleotides) that play a pivotal role in regulating gene expression. Understanding the miRNA interplays in oral cancers could augment the development of potential diagnostic, prognostic, and therapeutic tools. Liquid biopsy- a non-invasive approach that has been used lately, allows the determination of miRNAs in biological fluids that play essential roles in tumor suppression and cancer promotion. Herein, we summarize an update on the role of miRNAs in the diagnosis and treatment of oral cancer.


Assuntos
MicroRNAs , Neoplasias Bucais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/terapia , Prognóstico , Regulação Neoplásica da Expressão Gênica
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