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223 result(s) for "Exosomal miRNA"
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Role of exosomal microRNAs in lung cancer biology and clinical applications
Exosomes, small extracellular vesicles ranging from 30 to 150 nm, are secreted by various cell types, including tumour cells. Recently, microRNAs (miRNAs) were identified to be encapsulated and hence protected from degradation within exosomes. These exosomal miRNAs can be horizontally transferred to target cells, in which they subsequently modulate biological processes. Increasing evidence indicates that exosomal miRNAs play a critical role in modifying the microenvironment of lung cancers, possibly facilitating progression, invasion, angiogenesis, metastasis and drug resistance. In this review, we summarize the novel findings on exosomal miRNA functions during lung cancer initiation and progression. In addition, we highlight their potential role and challenges as biomarkers in lung cancer diagnosis, prognosis and drug resistance and as therapeutic agents.
The Detection of Urinary Exosomal miRNAs for Cancer Diagnostics and Prognostics
Liquid biopsy is a non-invasive diagnostic method that utilizes the detection and analysis of biomarkers in bodily fluids for the diagnosis and prognosis of various diseases. Exosomal microRNAs (miRNAs), which are remarkably stable because of the protection by extracellular vesicles (EVs), in liquid biopsy have gained considerable attention as they can regulate gene expression and serve as crucial biomarkers for the presence and progression of different types of cancer. Especially, urinary exosomal miRNAs have shown promising results as biomarkers for cancer from the urogenital system, such as bladder, renal tubular, and prostate. However, there are still significant challenges hindering the clinical utilization of urinary exosomal miRNA biomarkers, including improper sample handling, and data bias. Therefore, the detection procedure of urinary exosomal miRNAs needs to be standardized and thoroughly reviewed to ensure accurate and reliable clinical results. In this review, we have explored various detection procedures for urinary exosomal miRNAs, which have great potential as biomarkers for cancer diagnostics and prognostics.
Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma
Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.
Engineering strategies and optimized delivery of exosomes for theranostic application in nerve tissue
Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function and permanent paralysis. Conventional interventions, such as drug administration and cell-based therapy, exhibit limited effectiveness due to their inability to preserve post-implantation cell survival and impede the deterioration of adjacent tissues. Exosomes have recently emerged as powerful tools for tissue repair owing to their proteins and nucleic acids, as well as their unique phospholipid properties, which facilitate targeted delivery to recipient cells. Engineering exosomes, obtained by manipulating the parental cells or directly functionalizing exosomes, play critical roles in enhancing regenerative repair, reducing inflammation, and maintaining physiological homeostasis. Furthermore, exosomes have been shown to restore neurological function when used in combination with biomaterials. This paper primarily focuses on the engineering strategies and delivery routes of exosomes related to neural research and emphasizes the theranostic application of optimized exosomes in peripheral nerve, traumatic spinal cord, and brain injuries. Finally, the prospects of exosomes development and their combination with other approaches will be discussed to enhance our knowledge on their theranostic effectiveness in neurological diseases.
Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer
Background Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. Main text Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. Conclusion Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.
Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT
Background Metastasis is the main cause of lung cancer mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) are a component of the cancer microenvironment and contribute to cancer progression. Intratumoral hypoxia affects both cancer and stromal cells. Exosomes are recognized as mediators of intercellular communication. Here, we aim to further elucidate the communication between BMSC-derived exosomes and cancer cells in the hypoxic niche. Methods Exosomal miRNA profiling was performed using a microRNA array. Lung cancer cells and an in vivo mouse syngeneic tumor model were used to evaluate the effects of select exosomal microRNAs. Hypoxic BMSC-derived plasma exosomal miRNAs were assessed for their capacity to discriminate between cancer patients and non-cancerous controls and between cancer patients with or without metastasis. Results We demonstrate that exosomes derived from hypoxic BMSCs are taken by neighboring cancer cells and promote cancer cell invasion and EMT. Exosome-mediated transfer of select microRNAs, including miR-193a-3p, miR-210-3p and miR-5100, from BMSCs to epithelial cancer cells activates STAT3 signaling and increases the expression of mesenchymal related molecules. The diagnostic accuracy of individual microRNA showed that plasma exosomal miR-193a-3p can discriminate cancer patients from non-cancerous controls. A panel of these three plasma exosomal microRNAs showed a better diagnostic accuracy to discriminate lung cancer patients with or without metastasis than individual exosomal microRNA. Conclusions Exosome-mediated transfer of miR-193a-3p, miR-210-3p and miR-5100, could promote invasion of lung cancer cells by activating STAT3 signalling-induced EMT. These exosomal miRNAs may be promising noninvasive biomarkers for cancer progression.
Effect of exosomal miRNA on cancer biology and clinical applications
Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.
An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer
Background According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC. Methods We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training ( n  = 58) and a validation cohort ( n  = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs. Results A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70–0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients. Conclusions Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy.
Circulating Exosomal miRNA as Diagnostic Biomarkers of Neurodegenerative Diseases
Neurodegenerative diseases (NDDs) are a group of diseases caused by chronic and progressive degeneration of neural tissue. The main pathological manifestations are neuronal degeneration and loss in the brain and/or spinal cord. Common NDDs include Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS). The complicated pathological characteristics and different clinical manifestations of NDDs result in a lack of sensitive and efficient diagnostic methods. In addition, no sensitive biomarkers are available to monitor the course of NDDs, predict their prognosis, and monitor the therapeutic response. Despite extensive research in recent years, analysis of amyloid β (Aβ) and α-synuclein has failed to effectively improve NDD diagnosis. Although recent studies have indicated circulating miRNAs as promising diagnostic biomarkers of NDDs, the miRNA in the peripheral circulation is susceptible to interference by other components, making circulating miRNA results less consistent. Exosomes are small membrane vesicles with a diameter of approximately 30-100 nm that transport proteins, lipids, mRNA, and miRNA. Because recent studies have shown that exosomes have a double-membrane structure that can resist ribonuclease in the blood, giving exosomal miRNA high stability and making them resistant to degradation, they may become an ideal biomarker of circulating fluids. In this review, we discuss the applicability of circulating exosomal miRNAs as biomarkers, highlight the technical aspects of exosomal miRNA analysis, and review studies that have used circulating exosomal miRNAs as candidate diagnostic biomarkers of NDDs.
MicroRNAs and Exosomal microRNAs May BePossible Targetsto InvestigateinGestational Diabetes Mellitus
Xiyao Yang,1 Na Wu1,2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of China, Tel +86 18940258445, Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that occurs during the second or third trimester of pregnancy. As the incidence of GDM rises, so does the risk of maternal and fetal complications with short- and long-term consequences. As a result, early diagnosis and treatment of this condition are important to avoiding adverse pregnancy outcomes. Exosomes are tiny vesicles secreted by living cells which contain a variety of bioactive substances. They are released by cells to facilitate cell-to-cell communication and regulate a variety of biological processes such as cellular immune response, inflammatory response, and apoptosis, among others. Many studies have recently confirmed that changes in the expression and secretion of exosomal miRNAs can be used as novel markers for the diagnosis, prognosis, and treatment of GDM. In this review, we summarized the various roles of exosomal miRNAs and circulating miRNAs in GDM. We found that the changes in the expression of certain miRNAs could be used to diagnosing GDM. Exosomal miRNAs target metabolic pathways, resulting in insulin resistance. We also highlighted the potential for miRNAs and exosomal miRNAs to be used as biomarkers for diagnosis or therapeutic agents.Keywords: GDM, exosomal miRNA, biomarker, insulin resistance, pregnancy