Exosomal ncRNAs Research Articles

Exosomal Non-coding RNAs: A New Approach to Melanoma Diagnosis and Therapeutic Strategy.

Malignant melanoma (MM) is a highly aggressive cancer with a poor prognosis. Currently, although a variety of therapies are available for treating melanoma, MM is still a serious threat to the patient's life due to numerous factors, such as the recurrence of tumors, the emergence of drug resistance, and the lack of effective therapeutic agents. Exosomes are biologically active lipid-bilayer extracellular vesicles secreted by diverse cell types that mediate intercellular signal communication. Studies found that exosomes are involved in cancer by carrying multiple bioactive molecules, including non-- coding RNAs (ncRNAs). The ncRNAs have been reported to play an important role in regulating proliferation, angiogenesis, immune regulation, invasion, metastasis, and treatment resistance of tumors. However, the functional role of exosomal ncRNAs in MM remains unknown. Therefore, this review summarizes the current state of melanoma diagnosis, treatment, and the application of exosomal ncRNAs in MM patients, which may provide new insights into the mechanisms involved in melanoma progression and serve as biomarkers for diagnosis and therapeutic targets.

Advances in different adult stem cell-derived exosomal non-coding RNAs for the treatment of neurological disorders: a narrative review.

Neurological disorders are being increasingly recognized as major causes of death and disability around the world. Neurological disorders refer to a broad range of medical conditions that affect the brain and spinal cord. These disorders can have various causes, including genetic factors, infections, trauma, autoimmune reactions, or neurodegenerative processes. Each disorder has its own unique symptoms, progression, and treatment options. Optimal communication between interneurons and neuron-glia cells within the homeostatic microenvironment is of paramount importance. Within this microenvironment, exosomes play a significant role in promoting intercellular communication by transferring a diverse cargo of contents, including proteins, lipids, and non-coding RNAs (ncRNAs). Partially, nervous system homeostasis is preserved by various stem cell-derived exosomal ncRNAs, which include circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs). The diversity of these exosomal ncRNAs suggests their potential to influence multiple pathways and cellular processes within the nervous system. Stem cell-derived exosomes and their ncRNA contents have been investigated for potential therapeutic uses in neurological disorders, owing to their demonstrated capabilities in neuroprotection, neuroregeneration, and modulation of disease-related pathways. The ability of stem cell-derived exosomes to cross the blood-brain barrier makes them a promising delivery vehicle for therapeutic ncRNAs. This review aims to summarize the current understanding of different stem cell-derived exosomal ncRNAs and their therapeutic potential and clinical applications.

Exosomal Non-coding RNA Derived from Mesenchymal Stem Cells (MSCs) in Autoimmune Diseases Progression and Therapy; an Updated Review.

Inflammation and autoimmune diseases (AD) are common outcomes of an overactive immune system. Inflammation occurs due to the immune system reacting to damaging stimuli. Exosomes are being recognized as an advanced therapeutic approach for addressing an overactive immune system, positioning them as a promising option for treating AD. Mesenchymal stem cells (MSCs) release exosomes that have strong immunomodulatory effects, influenced by their cell of origin. MSCs-exosomes, being a cell-free therapy, exhibit less toxicity and provoke a diminished immune response compared to cell-based therapies. Exosomal non-coding RNAs (ncRNA), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are intricately linked to various biological and functional aspects of human health. Exosomal ncRNAs can lead to tissue malfunction, aging, and illnesses when they experience tissue-specific alterations as a result of various internal or external problems. In this study, we will examine current trends in exosomal ncRNA researches regarding AD. Then, therapeutic uses of MSCs-exosomal ncRNA will be outlined, with a particle focus on the underlying molecular mechanisms.

Bladder cancer: non-coding RNAs and exosomal non-coding RNAs.

Bladder cancer (BCa) is a highly prevalent type of cancer worldwide, and it is responsible for numerous deaths and cases of disease. Due to the diverse nature of this disease, it is necessary to conduct significant research that delves deeper into the molecular aspects, to potentially discover novel diagnostic and therapeutic approaches. Lately, there has been a significant increase in the focus on non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), due to their growing recognition for their involvement in the progression and manifestation of BCa. The interest in exosomes has greatly grown due to their potential for transporting a diverse array of active substances, including proteins, nucleic acids, carbohydrates, and lipids. The combination of these components differs based on the specific cell and its condition. Research indicates that using exosomes could have considerable advantages in identifying and forecasting BCa, offering a less invasive alternative. The distinctive arrangement of the lipid bilayer membrane found in exosomes is what makes them particularly effective for administering treatments aimed at managing cancer. In this review, we have tried to summarize different ncRNAs that are involved in BCa pathogenesis. Moreover, we highlighted the role of exosomal ncRNAs in BCa.

Exosomal noncoding RNAs: decoding their role in thyroid cancer progression.

Exosomes, as pivotal entities within the tumor microenvironment, orchestrate intercellular communication through the transfer of diverse molecules, among which non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs play a crucial role. These ncRNAs, endowed with regulatory functions, are selectively incorporated into exosomes. Emerging evidence underscores the significance of exosomal ncRNAs in modulating key oncogenic processes in thyroid cancer (TC), including proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunoediting. The unique composition of exosomes shields their cargo from enzymatic and chemical degradation, ensuring their integrity and facilitating their specific expression in plasma. This positions exosomal ncRNAs as promising candidates for novel diagnostic and prognostic biomarkers in TC. Moreover, the potential of exosomes in the therapeutic landscape of TC is increasingly recognized. This review aims to elucidate the intricate relationship between exosomal ncRNAs and TC, fostering a deeper comprehension of their mechanistic involvement. By doing so, it endeavors to propel forward the exploration of exosomal ncRNAs in TC, ultimately paving the way for innovative diagnostic and therapeutic strategies predicated on exosomes and their ncRNA content.

Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.

Lung cancer is the second most common form of cancer worldwide Research points to the pivotal role of non-coding RNAs (ncRNAs) in controlling and managing the pathology by controlling essential pathways. ncRNAs have all been identified as being either up- or downregulated among individuals suffering from lung cancer thus hinting that they may play a role in either promoting or suppressing the spread of the disease. Several ncRNAs could be effective non-invasive biomarkers to diagnose or even serve as effective treatment options for those with lung cancer, and several molecules have emerged as potential targets of interest. Given that ncRNAs are contained in exosomes and are implicated in the development and progression of the malady. Herein, we have summarized the role of ncRNAs in lung cancer. Moreover, we highlight the role of exosomal ncRNAs in lung cancer.

Exosomal noncoding RNAs in gynecological cancers: implications for therapy resistance and biomarkers.

Gynecologic cancers, including ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), pose a serious threat to women's health and quality of life due to their high incidence and lethality. Therapeutic resistance in tumors refers to reduced sensitivity of tumor cells to therapeutic drugs or radiation, which compromises the efficacy of treatment or renders it ineffective. Therapeutic resistance significantly contributes to treatment failure in gynecologic tumors, although the specific molecular mechanisms remain unclear. Exosomes are nanoscale vesicles released and received by distinct kinds of cells. Exosomes contain proteins, lipids, and RNAs closely linked to their origins and functions. Recent studies have demonstrated that exosomal ncRNAs may be involved in intercellular communication and can modulate the progression of tumorigenesis, aggravation and metastasis, tumor microenvironment (TME), and drug resistance. Besides, exosomal ncRNAs also have the potential to become significant diagnostic and prognostic biomarkers in various of diseases. In this paper, we reviewed the biological roles and mechanisms of exosomal ncRNAs in the drug resistance of gynecologic tumors, as well as explored the potential of exosomal ncRNAs acting as the liquid biopsy molecular markers in gynecologic cancers.

Adipose exosomal noncoding RNAs: Roles and mechanisms in metabolic diseases.

Exosomes are extracellular vesicles, measuring 40-160 nm in diameter, that are released by many cell types and tissues, including adipose tissue. Exosomes are critical mediators of intercellular communication and their contents are complex and diverse. In recent years, accumulating evidence has proved that multiple adipose tissue-derived exosomal noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in the pathogenesis of diverse metabolic diseases, such as obesity. In this narrative review, we focus on the adipose tissue-derived exosomal ncRNAs, especially exosomal miRNAs, and their dysregulation in multiple types of metabolic diseases. A deeper understanding of the role of adipose tissue-derived exosomal ncRNAs may help provide new diagnostic and treatment methods for metabolic diseases.

Clinical significance of exosomal noncoding RNAs in hepatocellular carcinoma: a narrative review.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, with poor prognosis owing to its high frequency of recurrence and metastasis. Moreover, most patients are diagnosed at an advanced stage owing to a lack of early detection markers. Exosomes, which are characterized by their cargos of stable intracellular messengers, such as DNA, RNA, proteins, and lipids, play a crucial role in regulating cell differentiation and HCC development. Recently, exosomal noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, have become increasingly important diagnostic, prognostic, and predictive markers of HCC. Herein, we discuss the clinical implications of exosomal ncRNAs, specifically those within the HCC regulatory network.

Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases.

Ferroptosis, an iron-dependent form of programmed cell death, introduces a novel perspective on cellular demise. This study investigates the regulatory network of exosomal non-coding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, in ferroptosis modulation. The primary goal is to examine the pathological roles of ferroptosis-related exosomal ncRNAs, particularly in ischemic reperfusion injuries. The research reveals intricate molecular interactions governing the regulatory interplay between exosomal ncRNAs and ferroptosis, elucidating their diverse roles in different non-malignant pathological contexts. Attention is given to their impact on diseases, including cardiac, cerebral, liver, and kidney ischemic injuries, as well as lung, wound, and neuronal injuries. Beyond theoretical exploration, the study provides insights into potential therapeutic applications, emphasizing the significance of mesenchymal stem cells (MSCs)-derived exosomes. Findings underscore the pivotal role of MSC-derived exosomal ncRNAs in modulating cellular responses related to ferroptosis regulation, introducing a cutting-edge dimension. This recognition emphasizes the importance of MSC-derived exosomes as crucial mediators with broad therapeutic implications. Insights unveil promising avenues for targeted interventions, capitalizing on the diverse roles of exosomal ncRNAs, providing a comprehensive foundation for future therapeutic strategies.

Exosomal noncoding RNAs as noninvasive biomarkers in bladder cancer: a diagnostic meta-analysis

BackgroundIn view of discordance consisting in different reports, a meta-analysis was conducted to comprehensively evaluate the diagnostic efficacy of exosomal noncoding RNAs (ncRNAs) in blood and urine in the detection of bladder cancer.MethodsEligible studies were acquired by systematic retrieval through PubMed, Cochrane Library, and Embase. The pooled diagnostic efficacy was appraised by reckoning the area under the summary receiver operating characteristic (SROC) curve. The latent sources of heterogeneity were probed by subgroup analyses and meta-regression. STATA 12.0, Meta-DiSc 1.4, and RevMan 5.3 were applied to carry out all statistical analyses and plots.ResultsA total of 46 studies from 15 articles comprising 2622 controls and 3015 bladder cancer patients were included in our meta-analysis. Exosomal ncRNAs in blood and urine represented relatively satisfactory diagnostic efficacy in detecting bladder cancer, with a pooled sensitivity of 0.75, a specificity of 0.79, and an area under the SROC curve (AUC) of 0.84. Exosomal microRNAs (miRNAs) exhibited better diagnostic value with a pooled AUC of 0.91 than that of exosomal long noncoding RNAs (lncRNAs). To some extent, the heterogeneity among studies was induced by exosomal ncRNA types (miRNA or lncRNA), exosomal ncRNA profiling (single- or multiple-ncRNA), sample size, specimen types, and ethnicity.ConclusionExosomal ncRNAs in blood and urine may play a vital role in diagnosing bladder cancer as prospective noninvasive biomarkers; nonetheless, their clinical performance needs to be confirmed by further massive proactive researches.

Diagnostic and Therapeutic Roles of Extracellular Vesicles and Their Enwrapped ncRNAs in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory disease whose precise pathogenesis remains mysterious. The involvement of epigenetic regulation in the pathogenesis of RA is one of the most anticipated findings, among which non-coding RNAs (ncRNAs) hold great application promise as diagnostic and therapeutic biomarkers for RA. Extracellular vesicles (EVs) are a heterogeneous group of nano-sized, membrane-enclosed vesicles that mediate intercellular communication and substance exchange, especially the transfer of ncRNAs from donor cells, thereby regulating the functional activities and biological processes of recipient cells. In light of the significant correlation between EVs, ncRNAs, and RA, we first documented expression levels of EVs and their-encapsulated ncRNAs in RA individuals, and methodically discussed their-implicated signaling pathways and phenotypic changes. The last but not least, we paied special attention to the therapeutic benefits of gene therapy reagents specifically imitating or silencing candidate ncRNAs with exosomes as carriers on RA animal models, and briefly highlighted their clinical application advantage and foreground. In conclusion, the present review may be conducive to a deeper comprehension of the diagnostic and therapeutic roles of EVs-enwrapped ncRNAs in RA, with special emphasis on exosomal ncRNAs, which may offer hints for the monitoring and treatment of RA.

Advances in Intercellular Communication Mediated by Exosomal ncRNAs in Cardiovascular Disease.

Cardiovascular diseases are a leading cause of worldwide mortality, and exosomes have recently gained attention as key mediators of intercellular communication in these diseases. Exosomes are double-layered lipid vesicles that can carry biomolecules such as miRNAs, lncRNAs, and circRNAs, and the content of exosomes is dependent on the cell they originated from. They can be involved in the pathophysiological processes of cardiovascular diseases and hold potential as diagnostic and monitoring tools. Exosomes mediate intercellular communication, stimulate or inhibit the activity of target cells, and affect myocardial hypertrophy, injury and infarction, ventricular remodeling, angiogenesis, and atherosclerosis. Exosomes can be released from various types of cells, including endothelial cells, smooth muscle cells, cardiomyocytes, fibroblasts, platelets, adipocytes, immune cells, and stem cells. In this review, we highlight the communication between different cell-derived exosomes and cardiovascular cells, with a focus on the roles of RNAs. This provides new insights for further exploring targeted therapies in the clinical management of cardiovascular diseases.

Exosomal non-coding RNAs in glioma progression: insights into tumor microenvironment dynamics and therapeutic implications.

Gliomas are the most common and deadly types of brain tumors, known for their extensive genetic and epigenetic variability, which poses considerable challenges for pharmacological treatment. Glioma heterogeneity is also related to their intricate and dynamic tumor microenvironment (TME), which comprises a diverse array of cell types, including immune cells, vascular cells, glial cells, and neural precursors, collectively influencing tumor behavior and progression. A pivotal aspect of this intercellular communication relies on the exchange of extracellular vesicles (EVs), which contain and transfer complex molecular cargoes typical of their cells of origin, such as proteins, lipids, carbohydrates, metabolites, and non-coding RNAs (ncRNAs), that encompass microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Glioma cells actively release EVs loaded with specific ncRNAs that can target genes and other ncRNAs in recipient cells residing within the TME. Among these recipient cells, prominent players include tumor-associated macrophages and microglia (TAMs), non-neoplastic astrocytes and endothelial cells. The intricate interplay between EVs derived from glioma cells and these recipient cells significantly contributes to the establishment of a tumor-permissive microenvironment, promoting tumor cell proliferation, migration, angiogenesis, and invasion, by targeting various downstream pathways. This review critically examines the current understanding of the intricate interplay between glioma, exosomal ncRNAs, and various components of the glioma TME. By shedding light on the roles of ncRNAs in mediating intercellular communication, this review underscores their significance in orchestrating TME transformation and highlights their potential as novel therapeutic targets for effectively tackling glioma progression.

The effects of intracellular and exosomal ncRNAs on cancer progression.

Altered gene expression as well as mislocalization of a gene's encoded product (proteins or noncoding RNAs (ncRNAs)) can lead to disease and cancer formation. Multiple studies have indicated that exosomes and their contents act as cell-to-cell communicators and play a key role in cancer progression. Moreover, exosomes contain several functional molecules, including ncRNAs. NcRNAs function as master regulators to coordinate cell growth, cell motility and drug resistance. However, intracellular ncRNAs, which can be transferred to recipient cells via exosomes (exosomal ncRNAs), mediate common/distinct downstream molecules, signaling pathways and functions that are less emphasized concepts in cancer development research. In this study, by using exosomes as a model, we comprehensively discuss the current knowledge regarding (1) the functional role of ncRNAs, both their intracellular and exosomal forms, in cancer progression, (2) the possible mechanism of ncRNA incorporation into exosomes and (3) the therapeutic applications and limitations of exosomes based on current knowledge.

Advances in the regulation of adipogenesis and lipid metabolism by exosomal ncRNAs and their role in related metabolic diseases.

Exosomes are membrane-bound extracellular vesicles released following the fusion of multivesicular bodies (MVBs) with the cell membrane. Exosomes transport diverse molecules, including proteins, lipids, DNA and RNA, and regulate distant intercellular communication. Noncoding RNA (ncRNAs) carried by exosomes regulate cell-cell communication in tissues, including adipose tissue. This review summarizes the action mechanisms of ncRNAs carried by exosomes on adipocyte differentiation and modulation of adipogenesis by exosomal ncRNAs. This study aims to provide valuable insights for developing novel therapeutics.

The pivotal role of EMT-related noncoding RNAs regulatory axes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a major health problem worldwide, being the leading cause of cancer-related deaths, with limited treatment options, especially in its advanced stages. Tumor resistance is closely associated with the activation of the EMT phenomenon and its reversal, being modulated by different molecules, including noncoding RNAs (ncRNAs). Noncoding RNAs have the potential to function as both tumor suppressors and oncogenic molecules, controlling the malignant potential of HCC cells. Basically, these molecules circulate in the tumor microenvironment, encapsulated in exosomes. Their impact on cell biology is more significant than originally expected, which makes related research rather complex. The temporal and spatial expression patterns, precise roles and mechanisms of specific ncRNAs encapsulated in exosomes remain primarily unknown in different stages of the disease. This review aims to highlight the recent advances in ncRNAs related to EMT and classifies the described mechanism as direct and indirect, for a better summarization. Moreover, we provide an overview of current research on the role of ncRNAs in several drug resistance-related pathways, including the emergence of resistance to sorafenib, doxorubicin, cisplatin and paclitaxel therapy. Nevertheless, we comprehensively discuss the underlying regulatory mechanisms of exosomal ncRNAs in EMT-HCC via intercellular communication pathways.

Chemotherapy-induced exosomal circBACH1 promotes breast cancer resistance and stemness via miR-217/G3BP2 signaling pathway

BackgroundChemoresistance involves metastasis and aggressiveness of breast cancer (BC). Chemotherapy-elicited exosomes have been reported to be associated with drug resistance and pro-metastatic capacity of BC cells. Non-coding RNAs (ncRNAs) are enriched in exosomes, which participated in generation, progression, and resistance of BC. However, the mechanism underlying the chemoresistance and metastasis in BC cells mediated by the BC-derived exosomal ncRNAs remained to be elucidated.MethodsThe effects of PTX-induced exosomal circBACH1 on BC cell function were assessed using RNA Binding Protein Immunoprecipitation (RIP), dual luciferase reporter gene, tube formation, CCK-8, and Western Blot assays. The circBACH1 and miR-217 expression levels were detected using quantitative real-time PCR (RT-qPCR) and Immunohistochemistry (IHC) assays in BC tissues and precancerous tissues of BC patients.ResultsCircBACH1 expression was increased in paclitaxel-treated BC-derived exosomes (PTX-EXO) and BC tissue. PTX-EXO was shown to promote PTX-resistance and angiogenesis through upregulation circBACH1. Downregulation of circBACH1 improved PTX-sensitiveness by suppressing the cell viability, stemness, migration, and angiogenesis of BC cells. Moreover, we found that miR-217 interacted with circBACH1 and targeted GTPase-activating SH3 domain-binding protein 2 (G3BP2) in BC cells. CircBACH1 combined miR-217 cotransfection suppressed the expression of G3BP2 proteins compared with circBACH1 treatment in MCF-7 cells. In addition, downregulation of G3BP2 suppressed BC cell migration.ConclusionsThese results demonstrated that PTX-induced exosomal circBACH1 promoted stemness and migration of BC cells by sponging miR-217 to upregulate the expression of G3BP2, which provided a new therapeutic target for PTX-resistance and progression of BC via circBACH1/miR-217/G3BP2 axis.

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

Abstract LB260: Assessing the suitability of our exosomal small ncRNAs to serve as biomarkers for breast cancer & elucidating the relationship of exosomal ncRNAs and cancer cells from t-47d and hc1143 cell lines

Abstract Background: Exosomes are known to play the role of cargo, carrying biologically important materials such as non-coding RNAs to their recipient cells. Small non-coding RNAs such as miRNA have been shown to exert strong effects on tumorigenesis. The liquid biopsy, which utilizes small RNAs from plasma exosomes, is therefore a promising tool for precision oncology. The purpose of this study is to discover exosomal miRNAs that serve as detection markers of breast cancer. Our hypothesis are 1) if exosomes play the role of cargo, then there should be an abundance of upregulated ncRNAs in exosomes that are also upregulated in the cancer cells themselves. 2) It is likely that the miRNAs in exosomes that are highly expressed have critical roles in cancer cell activity. We performed small RNA-seq and examined the ncRNAs inside cancer cells and exosomal ncRNAs secreted by cancer cells into the culture media. Methods: Two cancer cell lines T-47D and HCC1143, and primary Human Mammary Epithelial Cells (HMEC) were used. We prepared 5 samples of cellular RNA extracted from T-47D and HCC1143 and HMEC. We also extracted 8 samples of exosomal RNA from the media; which included those used for each cell culture and those never used for culture with or without FBS. Exosomes in FBS were depleted using Exosome Depletion Kits. The FASTQ files were uploaded onto QIAGEN GeneGlobe for analysis. The data was primarily normalized using geNorm. Results: Exosomal ncRNAs from both cancer cells were compared to exosomal ncRNAs from normal cells. A total of 879 ncRNAs were detected, 108 of which were significantly upregulated and 104 of which were downregulated in cancer cells. hsa-miR-196a-5p is a ncRNA that had a fold-change of 84.08. Prior studies suggest that this miRNA is associated with MIR196A2 methylation and affects the malignancy of many types of cancers. Comparing cancer exosomal ncRNAs vs. ncRNAs inside cancer cells, a total of 879 ncRNAs were found with a FDR q-value <0.05 and cut-off of 2 fold change. 251 ncRNAs were significantly upregulated in the exosomes. hsa-miR-1-3p had a fold change value of 4025.68 and an associated p-value of 0.0002. High levels of hsa-miR-1-3p are known to be associated with large tumors and is strongly correlated to a lower breast cancer survival rate. Conclusions: The preliminary results indicate that there were significant differences between exosomal ncRNAs from normal cells and exosomal ncRNAs from cancer cells. The data suggests that exosomal ncRNAs are a promising source of prognostic biomarkers for breast cancer as ncRNAs with a high fold change are repeatedly validated to have a significant impact on breast cancer progression. The data supports our hypothesis that the upregulation of ncRNAs in cancer cells & exosomes is linked to cancer activity. The results will be scrutinized further, as other avenues for data analysis will be explored. The next step in our experiment will be to check the cancer survival rates with the TCGA database and attempt to validate our hypothesis through further cell culture experiments. Citation Format: Ken D. Kobayashi, Mayumi Jijiwa, Masaki Nasu, Youping Deng. Assessing the suitability of our exosomal small ncRNAs to serve as biomarkers for breast cancer & elucidating the relationship of exosomal ncRNAs and cancer cells from t-47d and hc1143 cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB260.