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Transcripts longer than 200 nucleotides that are not translated into proteins are known as long non-coding RNAs, or lncRNAs. Now, they are becoming more significant as important regulators of gene expression, and as a result, of many biological processes in both healthy and pathological circumstances, such as blood malignancies. Through controlling alternative splicing, transcription, and translation at the post-transcriptional level, lncRNAs have an impact on the expression of genes. In multiple myeloma (MM), the majority of lncRNAs is elevated and promotes the proliferation, adhesion, drug resistance and invasion of MM cells by blocking apoptosis and altering the tumor microenvironment (TME). To control mRNA splicing, stability, and translation, they either directly attach to the target mRNA or transfer RNA-binding proteins (RBPs). By expressing certain miRNA-binding sites that function as competitive endogenous RNAs (ceRNAs), most lncRNAs mimic the actions of miRNAs. Here, we highlight lncRNAs role in the MM pathogenesis with emphasize on their capacity to control the molecular mechanisms known as "hallmarks of cancer," which permit earlier tumor initiation and progression and malignant cell transformation.
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Mieloma Múltiple , ARN Largo no Codificante , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Humanos , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genéticaRESUMEN
While intensity-modulated radiation therapy-based comprehensive therapy increases outcomes, cancer patients still have a low five-year survival rate and a high recurrence rate. The primary factor contributing to cancer patients' poor prognoses is radiation resistance. A class of endogenous non-coding RNAs, known as microRNAs (miRNAs), controls various biological processes in eukaryotes. These miRNAs influence tumor cell growth, death, migration, invasion, and metastasis, which controls how human carcinoma develops and spreads. The correlation between the unbalanced expression of miRNAs and the prognosis and sensitivity to radiation therapy is well-established. MiRNAs have a significant impact on the regulation of DNA repair, the epithelial-to-mesenchymal transition (EMT), and stemness in the tumor radiation response. But because radio resistance is a complicated phenomena, further research is required to fully comprehend these mechanisms. Radiation response rates vary depending on the modality used, which includes the method of delivery, radiation dosage, tumor stage and grade, confounding medical co-morbidities, and intrinsic tumor microenvironment. Here, we summarize the possible mechanisms through which miRNAs contribute to human tumors' resistance to radiation.
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A complex sequence of occurrences, including host genetic vulnerability, Helicobacter pylori infection, and other environmental variables, culminate in gastric cancer (GC). The development of several genetic and epigenetic changes in oncogenes and tumor suppressor genes causes dysregulation of several signaling pathways, which upsets the cell cycle and the equilibrium between cell division and apoptosis, leading to GC. Developments in computational biology and RNA-seq technology enable quick detection and characterization of long non-coding RNAs (lncRNAs). Recent studies have shown that long non-coding RNAs (lncRNAs) have multiple roles in the development of gastric cancer. These lncRNAs interact with molecules of protein, RNA, DNA, and/or combinations. This review article explores several gastric cancer-associated lncRNAs, such as ADAMTS9-AS2, UCA1, XBP-1, and LINC00152. These various lncRNAs could change GC cell apoptosis, migration, and invasion features in the tumor microenvironment. This review provides an overview of the most recent research on lncRNAs and GC cell apoptosis, migration, invasion, and drug resistance, focusing on studies conducted in cancer cells and healthy cells during differentiation.
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Apoptosis , Regulación Neoplásica de la Expresión Génica , MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Humanos , ARN Largo no Codificante/genética , MicroARNs/genética , Apoptosis/genética , Microambiente Tumoral/genética , Movimiento Celular/genética , Transducción de Señal/genética , Resistencia a Antineoplásicos/genéticaRESUMEN
Glaucoma, an irreversible optic neuropathy, primarily affects retinal ganglion cells (RGC) and causes vision loss and blindness. The damage to RGCs in glaucoma occurs by various mechanisms, including elevated intraocular pressure, oxidative stress, inflammation, and other neurodegenerative processes. As the disease progresses, the loss of RGCs leads to vision loss. Therefore, protecting RGCs from damage and promoting their survival are important goals in managing glaucoma. In this regard, resveratrol (RES), a polyphenolic phytoalexin, exerts antioxidant effects and slows down the evolution and progression of glaucoma. The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina. Additionally, RES plays protective roles in RGCs by promoting cell growth, reducing apoptosis, and decreasing oxidative stress in H2O2-exposed RGCs. RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways. RES could alleviate retinal function impairment by suppressing the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway. Therefore, RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.
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Glaucoma , Fármacos Neuroprotectores , Resveratrol , Células Ganglionares de la Retina , Resveratrol/farmacología , Resveratrol/uso terapéutico , Células Ganglionares de la Retina/efectos de los fármacos , Glaucoma/tratamiento farmacológico , Animales , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacosRESUMEN
It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug's mode of action, and make predictions about future approaches to targeting B-cells other than depletion.
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Enfermedades Autoinmunes , Linfocitos B , Depleción Linfocítica , Animales , Humanos , Antígenos CD19/inmunología , Antígenos CD20/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Factor Activador de Células B/inmunología , Linfocitos B/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Depleción Linfocítica/métodos , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/terapiaRESUMEN
Tumor-mediated immunosuppression is a fundamental obstacle to the development of dendritic cell (DC)-based cancer vaccines, which despite their ability to stimulate host anti-tumor CD8 T cell immunity, have not been able to generate meaningful therapeutic responses. Exosomes are inactive membrane vesicles that are nanoscale in size and are produced by the endocytic pathway. They are essential for intercellular communication. Additionally, DC-derived exosomes (DEXs) contained MHC class I/II (MHCI/II), which is frequently complexed with antigens and co-stimulatory molecules and is therefore able to prime CD4 and CD8 T cells that are specific to particular antigens. Indeed, vaccines with DEXs have been shown to exhibit better anti-tumor efficacy in eradicating tumors compared to DC vaccines in pre-clinical models of digestive system tumors. Also, there is room for improvement in the tumor antigenic peptide (TAA) selection process. DCs release highly targeted exosomes when the right antigenic peptide is chosen, which could aid in the creation of DEX-based antitumor vaccines that elicit more targeted immune responses. Coupled with their resistance to tumor immunosuppression, DEXs-based cancer vaccines have been heralded as the superior alternative cell-free therapeutic vaccines over DC vaccines to treat digestive system tumors. In this review, current studies of DEXs cancer vaccines as well as potential future directions will be deliberated.
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Vacunas contra el Cáncer , Células Dendríticas , Exosomas , Exosomas/inmunología , Humanos , Células Dendríticas/inmunología , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Neoplasias del Sistema Digestivo/inmunología , Neoplasias del Sistema Digestivo/terapia , Neoplasias del Sistema Digestivo/patología , Animales , Inmunoterapia/métodosRESUMEN
It has been suggested that the long non-coding RNAs (lncRNAs), such as colorectal neoplasia differentially expressed (CRNDE), may contribute to the formation of human cancer. It is yet unknown, though, what therapeutic significance CRNDE expression has for different forms of cancer. CRNDE has recently been proposed as a possible diagnostic biomarker and prognostic pred for excellent specificity and sensitivity in cancer tissues and plasma. To provide the groundwork for potential future therapeutic uses of CRNDE, we briefly overview its biological action and related cancer-related pathways. Next, we mainly address the impact of CRNDE on the epithelial-mesenchymal transition (EMT). The epithelial-mesenchymal transition, or EMT, is an essential biological mechanism involved in the spread of cancer.
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ARN Largo no Codificante , Humanos , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Procesos Neoplásicos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Ovarian cancer continues to be a difficult medical issue that affects millions of individuals worldwide. Important platforms for cancer immunotherapy include checkpoint inhibitors, chimeric antigen receptor T cells, bispecific antibodies, cancer vaccines, and other cell-based treatments. To avoid numerous infectious illnesses, conventional vaccinations based on synthetic peptides, recombinant subunit vaccines, and live attenuated and inactivated pathogens are frequently utilized. Vaccine manufacturing processes, however, are not entirely safe and carry a significant danger of contaminating living microorganisms. As a result, the creation of substitute vaccinations is required for both viral and noninfectious illnesses, including cancer. Recently, there has been testing of nucleic acid vaccines, or NAVs, as a cancer therapeutic. Tumor antigens (TAs) are genetically encoded by DNA and mRNA vaccines, which the host uses to trigger immune responses against ovarian cancer cells that exhibit the TAs. Despite being straightforward, safe, and easy to produce, NAVs are not currently thought to be an ideal replacement for peptide vaccines. Some obstacles to this strategy include selecting the appropriate therapeutic agents (TAs), inadequate immunogenicity, and the immunosuppressive characteristic of ovarian cancer. We focus on strategies that have been employed to increase NAVs' effectiveness in the fight against ovarian cancer in this review.
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Vacunas contra el Cáncer , Neoplasias Ováricas , Humanos , Femenino , Vacunación Basada en Ácidos Nucleicos , Neoplasias Ováricas/tratamiento farmacológico , Antígenos de Neoplasias , Vacunas contra el Cáncer/uso terapéuticoRESUMEN
Head and neck cancer (HNC) refers to the epithelial malignancies of the upper aerodigestive tract. HNCs have a constant yet slow-growing rate with an unsatisfactory overall survival rate globally. The development of new blood vessels from existing blood conduits is regarded as angiogenesis, which is implicated in the growth, progression, and metastasis of cancer. Aberrant angiogenesis is a known contributor to human cancer progression. Representing a promising therapeutic target, the blockade of angiogenesis aids in the reduction of the tumor cells oxygen and nutrient supplies. Despite the promise, the association of existing anti-angiogenic approaches with severe side effects, elevated cancer regrowth rates, and limited survival advantages is incontrovertible. Exosomes appear to have an essential contribution to the support of vascular proliferation, the regulation of tumor growth, tumor invasion, and metastasis, as they are a key mediator of information transfer between cells. In the exocrine region, various types of noncoding RNAs (ncRNAs) identified to be enriched and stable and contribute to the occurrence and progression of cancer. Mounting evidence suggest that exosome-derived ncRNAs are implicated in tumor angiogenesis. In this review, the characteristics of angiogenesis, particularly in HNC, and the impact of ncRNAs on HNC angiogenesis will be outlined. Besides, we aim to provide an insight on the regulatory role of exosomes and exosome-derived ncRNAs in angiogenesis in different types of HNC.
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Exosomas , Neoplasias de Cabeza y Cuello , ARN Largo no Codificante , Humanos , Exosomas/genética , Angiogénesis , ARN no Traducido/genética , Neoplasias de Cabeza y Cuello/genéticaRESUMEN
The failure of a titanium implant is often attributed to inflammatory reactions following implantation. This study focuses on the synthesis of a polyethylene glycol (PEG) layer on porous titanium dioxide (TiO2) coatings using plasma electrolytic oxidation (PEO). This PEG layer serves as a foundation for a drug-eluting platform designed to respond to pH stimuli during inflammation. Betamethasone (BET), a widely used anti-inflammatory drug, was loaded onto the pH-responsive functional PEG layers. The application of the PEG-BET layer onto TiO2 coatings through the vacuum dip coating method resulted in a pH-sensitive sustained release of BET over a 30-day period. Notably, the release rates were 81% at pH 5.0 and 55% at pH 7.2. Electrochemical corrosion tests conducted in both normal and acidic inflammatory solutions demonstrated that duplex composite coatings offer superior protection compared to simple oxide coatings. In a pH 5.0 solution, corrosion current density measurements revealed values of 1.75 µA cm-2 (PEO/PEG-BET), 8.87 µA cm-2 (PEO), and 49.17 µA cm-2 (bare titanium). These results highlight the effectiveness of the PEO/PEG-BET layer in sealing pores within PEO coatings, subsequently reducing the infiltration of corrosive ions in inflammatory environments.
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Pre-messenger RNA molecules are back-spliced to create circular RNAs, which are non-coding RNA molecules. After a thorough investigation, it was discovered that these circRNAs have critical biological roles. CircRNAs have a variety of biological functions, including their ability to operate as microRNA sponges, interact with proteins to alter their stabilities and activities, and provide templates for the translation of proteins. Evidence supports a link between the emergence of numerous diseases, including various cancer types, and dysregulated circRNA expression. It is commonly known that a significant contributing element to cancer development is the disruption of numerous molecular pathways essential for preserving cellular and tissue homeostasis. The dysregulation of multiple biological processes is one of the hallmarks of cancer, and the molecular pathways linked to these processes are thought to be promising targets for therapeutic intervention. The biological and carcinogenic effects of circRNAs in the context of cancer are thoroughly reviewed in this article. Specifically, we highlight circRNAs' involvement in signal transduction pathways and their possible use as novel biomarkers for the early identification and prognosis of human cancer.
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MicroARNs , Neoplasias , Humanos , ARN Circular/genética , Neoplasias/genética , Neoplasias/patología , ARN Mensajero , Transducción de Señal/genéticaRESUMEN
Having been involved in complex cellular regulatory networks and cell-to-cell communications, non-coding RNAs (lncRNAs) have become functional carriers that transmit information between cells and tissues, modulate tumor microenvironments, encourage angiogenesis and invasion, and make tumor cells more resistant to drugs. Immune cells' exosomal lncRNAs may be introduced into tumor cells to influence the tumor's course and the treatment's effectiveness. Research has focused on determining if non-coding RNAs affect many target genes to mediate regulating recipient cells. The tumor microenvironment's immune and cancer cells are influenced by lncRNAs, which may impact a treatment's efficacy. The lncRNA-mediated interaction between cancer cells and immune cells invading the tumor microenvironment has been the subject of numerous recent studies. On the other hand, tumor-derived lncRNAs' control over the immune system has not gotten much attention and is still a relatively new area of study. Tumor-derived lncRNAs are recognized to contribute to tumor immunity, while the exact mechanism is unclear.
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Neoplasias , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Neoplasias/genética , Neoplasias/patología , Sistema Inmunológico/patología , Microambiente Tumoral/genéticaRESUMEN
This comprehensive article explores the complex field of glioma treatment, with a focus on the important roles of non-coding RNAsRNAs (ncRNAs) and exosomes, as well as the potential synergies of immunotherapy. The investigation begins by examining the various functions of ncRNAs and their involvement in glioma pathogenesis, progression, and as potential diagnostic biomarkers. Special attention is given to exosomes as carriers of ncRNAs and their intricate dynamics within the tumor microenvironment. The exploration extends to immunotherapy methods, analyzing their mechanisms and clinical implications in the treatment of glioma. By synthesizing these components, the article aims to provide a comprehensive understanding of how ncRNAs, exosomes, and immunotherapy interact, offering valuable insights into the evolving landscape of glioma research and therapeutic strategies.
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Exosomas , Vesículas Extracelulares , Glioma , Humanos , Inmunoterapia , Glioma/terapia , Microambiente TumoralRESUMEN
MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression. They are involved in a wide range of biological processes, including development, differentiation, cell cycle regulation, and response to stress. Numerous studies have demonstrated that miRNAs are present in different bodily fluids, which could serve as an important biomarker. The advancement of techniques and strategies for the identification of cancer-associated miRNAs in human specimens offers a novel opportunity to diagnose cancer in early stages, predict patient prognosis and evaluate response to treatment. Isothermal techniques including loop-mediated isothermal amplification (LAMP), rolling circle amplification (RCA), or recombinase polymerase amplification (RPA) offer simplicity, efficiency, and rapidity in miRNA detection processes. In contrast to traditional PCR (polymerase chain reaction), these techniques analysis and quantify miRNA molecules in specimens using a single constant temperature. In this comprehensive review, we summarized the recent advances in cancer-related miRNA detection via highly sensitive isothermal amplification methods by more focusing on the involved mechanism.
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MicroARNs , Neoplasias , Humanos , MicroARNs/metabolismo , Neoplasias/diagnóstico , Neoplasias/genéticaRESUMEN
The regulation of signal transmission and biological processes, such as cell proliferation, apoptosis, metabolism, migration, and angiogenesis are greatly influenced by the PI3K/AKT signaling pathway. Highly conserved endogenous non-protein-coding RNAs known as microRNAs (miRNAs) have the ability to regulate gene expression by inhibiting mRNA translation or mRNA degradation. MiRNAs serve key role in PI3K/AKT pathway as upstream or downstream target, and aberrant activation of this pathway contributes to the development of cancers. A growing body of research shows that miRNAs can control the PI3K/AKT pathway to control the biological processes within cells. The expression of genes linked to cancers can be controlled by the miRNA/PI3K/AKT axis, which in turn controls the development of cancer. There is also a strong correlation between the expression of miRNAs linked to the PI3K/AKT pathway and numerous clinical traits. Moreover, PI3K/AKT pathway-associated miRNAs are potential biomarkers for cancer diagnosis, therapy, and prognostic evaluation. The role and clinical applications of the PI3K/AKT pathway and miRNA/PI3K/AKT axis in the emergence of cancers are reviewed in this article.
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MicroARNs , Neoplasias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/genética , Neoplasias/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Apoptosis/genética , Línea Celular TumoralRESUMEN
Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development. Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model. Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195. Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.
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Modulatory signaling pathway such as T cell immunoreceptor with Ig and ITIM domains (TIGIT), Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4), P53 signaling and TIM (T-cell immunoglobin and mucin domain) are important in normal pregnancy and loss of their functions or dysregulation of related genes can lead to some disorders. Inflammation is a process by which your body's white blood cells and the things they make protect you from infection from outside invaders, such as bacteria and viruses. Some cellular and molecular signaling have been categorized to demonstrate the mechanism that protects tolerance to antigens. lncRNAs significantly impact physiological processes like immunity and metabolism, and are linked to tumors, cardiovascular diseases, nervous system disorders, and nephropathy.In this review article, we summarized recent studies about the role of TIGIT, CTLA-4, P53 and TIM regulatory molecules and reviewed dysregulation of these pathway in diseases.We will also talk about the role of lncRNAs and mesenchymal stem cells.
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One of the best treatments for inflammatory diseases such as COVID-19, respiratory diseases and brain diseases is treatment with stem cells. Here we investigate the effect of stem cell therapy in the treatment of brain diseases.Preclinical studies have shown promising results, including improved functional recovery and tissue repair in animal models of neurodegenerative diseases, strokes,and traumatic brain injuries. However,ethical implications, safety concerns, and regulatory frameworks necessitate thorough evaluation before transitioning to clinical applications. Additionally, the complex nature of the brain and its intricate cellular environment present unique obstacles that must be overcome to ensure the successful integration and functionality of genetically engineered MSCs. The careful navigation of this path will determine whether the application of genetically engineered MSCs in brain tissue regeneration ultimately lives up to the hype surrounding it.
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COVID-19 , Células Madre Mesenquimatosas , ARN Largo no Codificante , Accidente Cerebrovascular , Animales , SecretomaRESUMEN
Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as microRNAs (miRNAs) regulates gene expression at the post-transcriptional level by binding only to messenger RNAs (mRNAs). Due to their capacity to target numerous genes, miRNAs have the potential to play a significant role in the development of tumors by controlling several biological processes, including angiogenesis, drug resistance, metastasis, apoptosis, proliferation, and drug resistance. According to several recent studies, miRNA-214 has been linked to the emergence and spread of tumors. The human genome's q24.3 arm contains the DNM3 gene, which is about 6 kb away and includes the microRNA-214. Its primary purpose was the induction of apoptosis in cancerous cells. The multifaceted and complex functions of miR-214 as a modulator in neoplastic conditions have been outlined in the current review.