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1.
Oncol Res ; 32(6): 1011-1019, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827323

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Neuroendocrino , Biología Computacional , MicroARNs , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/patología , MicroARNs/genética , Biomarcadores de Tumor/genética , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/diagnóstico , Pronóstico , Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica , Internet , Terapia Molecular Dirigida
2.
Int Rev Cell Mol Biol ; 386: 133-165, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38782498

RESUMEN

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.


Asunto(s)
MicroARNs , Neoplasias , Transducción de Señal , Humanos , MicroARNs/metabolismo , MicroARNs/genética , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Neoplasias/genética , Animales , Regulación Neoplásica de la Expresión Génica
3.
Microrna ; 13(1): 33-55, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38284737

RESUMEN

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.


Asunto(s)
Biología Computacional , Redes Reguladoras de Genes , MicroARNs , MicroARNs/genética , Humanos , Biología Computacional/métodos , Redes Reguladoras de Genes/genética , Minería de Datos/métodos , Regulación Neoplásica de la Expresión Génica/genética , Mapas de Interacción de Proteínas/genética
4.
Biomed Pharmacother ; 171: 116165, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38237348

RESUMEN

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.


Asunto(s)
MicroARNs , Neoplasias , Humanos , MicroARNs/genética , Neoplasias/metabolismo , Genes Supresores de Tumor , Oncogenes , Proteínas Oncogénicas/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral
5.
Artículo en Inglés | MEDLINE | ID: mdl-38265389

RESUMEN

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.

6.
Pathol Res Pract ; 253: 154995, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38113765

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama , Exosomas , Vesículas Extracelulares , Femenino , Humanos , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Exosomas/metabolismo , Transducción de Señal , Comunicación Celular , Vesículas Extracelulares/metabolismo , Microambiente Tumoral
7.
Mol Biotechnol ; 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38133750

RESUMEN

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.

8.
Diagnostics (Basel) ; 13(19)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37835815

RESUMEN

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.

9.
J Oral Maxillofac Pathol ; 27(2): 364-373, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37854932

RESUMEN

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.

10.
Genes (Basel) ; 14(7)2023 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-37510280

RESUMEN

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.


Asunto(s)
MicroARNs , Neoplasias , Humanos , Animales , Perros , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica
11.
Cancer Metastasis Rev ; 42(3): 725-740, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37490255

RESUMEN

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.


Asunto(s)
Carcinoma Ductal Pancreático , MicroARNs , Neoplasias Pancreáticas , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Biomarcadores , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas
12.
Genes (Basel) ; 14(3)2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36980984

RESUMEN

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.


Asunto(s)
Leiomiomatosis , MicroARNs , Neoplasias Uterinas , Femenino , Humanos , Leiomiomatosis/genética , Leiomiomatosis/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Útero/metabolismo , MicroARNs/genética , MicroARNs/metabolismo
13.
J Pharm Anal ; 13(11): 1235-1251, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38174117

RESUMEN

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.

14.
Crit Rev Oncol Hematol ; 180: 103850, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36261117

RESUMEN

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.


Asunto(s)
MicroARNs , Neoplasias de la Boca , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Detección Precoz del Cáncer , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Neoplasias de la Boca/terapia , Pronóstico , Regulación Neoplásica de la Expresión Génica
15.
Front Immunol ; 13: 913951, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36189271

RESUMEN

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.


Asunto(s)
MicroARNs , Neoplasias , Genes Supresores de Tumor , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/terapia , Oncogenes , ARN Mensajero , Microambiente Tumoral/genética
16.
J Pers Med ; 12(9)2022 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-36143213

RESUMEN

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.

17.
Front Pharmacol ; 13: 844104, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370727

RESUMEN

Indocyanine green (ICG) is a nontoxic registered photosensitizer used as a diagnostic tool and for photodynamic therapy (PDT). Hypoxia is one the main factors affecting PDT efficacy. Perfluorodecalin emulsion (Perftoran®) is a known oxygen carrier. This study investigated the effect of Perftoran® on ICG/PDT efficacy in presence and absence of Perftoran® via evaluation of phototoxicity by MTT; hypoxia estimation by pimonidazole, HIF-1α/ß by ELISA, and 17 miRNAs (tumor suppressors, oncomiRs, and hypoxamiRs) were analyzed by qPCR. Compared to ICG/PDT, Perftoran®/ICG/PDT led to higher photocytotoxicity, inhibited pimonidazole hypoxia adducts, inhibited HIF-1α/ß concentrations, induced the expression of tumor-suppressing miRNAs let-7b/d/f/g, and strongly inhibited the pro-hypoxia miRNA let-7i. Additionally, Perftoran®/ICG/PDT suppressed the expression of the oncomiRs miR-155, miR-30c, and miR-181a and the hypoxamiRs miR-210 and miR-21 compared to ICG/PDT. In conclusion, Perftoran® induced the phototoxicity of ICG/PDT and inhibited ICG/PDT-hypoxia via suppressing HIF-α/ß, miR-210, miR-21, let-7i, miR-15a, miR-30c, and miR-181a and by inducing the expression of let-7d/f and miR-15b.

18.
Cells ; 11(6)2022 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-35326459

RESUMEN

Small noncoding RNAs, as post-translational regulators of many target genes, are not only markers of neoplastic disease initiation and progression, but also markers of response to anticancer therapy. Hundreds of miRNAs have been identified as biomarkers of drug resistance, and many have demonstrated the potential to sensitize cancer cells to therapy. Their properties of modulating the response of cells to therapy have made them a promising target for overcoming drug resistance. Several methods have been developed for the delivery of miRNAs to cancer cells, including introducing synthetic miRNA mimics, DNA plasmids containing miRNAs, and small molecules that epigenetically alter endogenous miRNA expression. The results of studies in animal models and preclinical studies for solid cancers and hematological malignancies have confirmed the effectiveness of treatment protocols using microRNA. Nevertheless, the use of miRNAs in anticancer therapy is not without limitations, including the development of a stable nanoconstruct, delivery method choices, and biodistribution. The aim of this review was to summarize the role of miRNAs in cancer treatment and to present new therapeutic concepts for these molecules. Supporting anticancer therapy with microRNA molecules has been verified in numerous clinical trials, which shows great potential in the treatment of cancer.


Asunto(s)
MicroARNs , Neoplasias , Animales , MicroARNs/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Distribución Tisular
19.
Pharmaceutics ; 13(12)2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34959401

RESUMEN

Lung cancer is one of the most commonly diagnosed cancers and is responsible for a large number of deaths worldwide. The pathogenic mechanism of lung cancer is complex and multifactorial in origin. Thus, various signaling pathways as targets for therapy are being examined, and many new drugs are in the pipeline. However, both conventional and target-based drugs have been reported to present significant adverse effects, and both types of drugs can affect the clinical outcome in addition to patient quality of life. Recently, miRNA has been identified as a promising target for lung cancer treatment. Therefore, miRNA mimics, oncomiRs, or miRNA suppressors have been developed and studied for possible anticancer effects. However, these miRNAs also suffer from the limitations of low stability, biodegradation, thermal instability, and other issues. Thus, nanocarrier-based drug delivery for the chemotherapeutic drug delivery in addition to miRNA-based systems have been developed so that existing limitations can be resolved, and enhanced therapeutic outcomes can be achieved. Thus, this review discusses lung cancer's molecular mechanism, currently approved drugs, and their adverse effects. We also discuss miRNA biosynthesis and pathogenetic role, highlight pre-clinical and clinical evidence for use of miRNA in cancer therapy, and discussed limitations of this therapy. Furthermore, nanocarrier-based drug delivery systems to deliver chemotherapeutic drugs and miRNAs are described in detail. In brief, the present review describes the mechanism and up-to-date possible therapeutic approaches for lung cancer treatment and emphasizes future prospects to bring these novel approaches from bench to bedside.

20.
Genes (Basel) ; 12(12)2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34946938

RESUMEN

Oral cancer is a common human malignancy that still maintains an elevated mortality rate despite scientific progress. Tumorigenesis is driven by altered gene expression patterns of proto-oncogenes and tumor-suppressor genes. MicroRNAs, a class of short non-coding RNAs involved in gene regulation, seem to play important roles in oral cancer development, progression, and tumor microenvironment modulation. As properties of microRNAs render them stable in diverse liquid biopsies, together with their differential expression signature in cancer cells, these features place microRNAs at the top of promising biomarkers for diagnostic and prognostic values. In this review, we highlight eight expression levels and functions of the most relevant microRNAs involved in oral cancer development, progression, and microenvironment sustainability. Furthermore, we emphasize the potential of using these small RNA species as non-invasive biomarkers for the early detection of oral cancerous lesions. Conclusively, we highlight the perspectives and limitations of microRNAs as novel diagnostic tools, as well as therapeutic models.


Asunto(s)
MicroARNs/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Biopsia Líquida , MicroARNs/metabolismo , Neoplasias de la Boca/metabolismo , Pronóstico , Transcriptoma/genética , Microambiente Tumoral
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