As cancer incidence and mortality rates rise, there is an urgent need to develop effective immunotherapy strategies. Circular RNA (circRNA), a newly identified type of non-coding RNA, is abundant within cells and can be released via exosomes, facilitating communication between cells. Studies have demonstrated that exosomal circRNAs can alter the tumor microenvironment and modulate immune responses by influencing the functions of T cells, natural killer (NK) cells, and macrophages, thereby enabling tumors to evade the immune system. Moreover, exosomal circRNAs show potential as diagnostic biomarkers and therapeutic targets for cancer. This review summarizes the regulatory roles of exosomal circRNAs in immune cells and their potential applications in cancer progression and treatment, highlighting their promise in improving cancer immunotherapy. Future research should concentrate on understanding the mechanisms of key exosomal circRNAs and developing targeted immunotherapy methods.

Exosomal circular RNA (circRNAs) are pivotal in cancer biology, and tumor pathophysiology. These stable, non-coding RNAs encapsulated in exosomes participated in cancer progression, tumor growth, metastasis, drug sensitivity and the tumor microenvironment (TME). Their presence in bodily fluids positions them as potential non-invasive biomarkers, revealing the molecular dynamics of cancers. Research in exosomal circRNAs is reshaping our understanding of neoplastic intercellular communication. Exploiting the natural properties of exosomes for targeted drug delivery and disrupting circRNA-mediated pro-tumorigenic signaling can develop new treatment modalities. Therefore, ongoing exploration of exosomal circRNAs in cancer research is poised to revolutionize clinical management of cancer. This emerging field offers hope for significant breakthroughs in cancer care. This review underscores the critical role of exosomal circRNAs in cancer biology and drug resistance, highlighting their potential as non-invasive biomarkers and therapeutic targets that could transform the clinical management of cancer.

Esophageal cancer (EC) is one of the most fatal malignancies worldwide, with a dramatic increase in incidence in the western world occurring over the past few decades. Chromosome instability (CIN) is a major contributor to EC progression, drug resistance, relapse, and the development of intratumoral heterogeneity. This study revealed a striking elevation of AURKB expression in EC patients, with a strong correlation to poor clinical outcomes. AURKB overexpression promoted cellular proliferation and induced drug resistance in both cell culture and animal models. Conversely, genetic targeting of AURKB abrogated these effects. Mechanistically, enforced AURKB expression triggered CIN, a key driver of poor EC outcomes, primarily through CEP250 phosphorylation. Interestingly, we identified a novel circular form of AURKB (circAURKB_288aa) harboring the AURKB kinase domain and encoding a 288-amino acid protein. Elevated levels of circAURKB_288aa in EC peripheral blood samples mirrored poor patient outcomes and synergistically enhanced CIN alongside AURKB. Furthermore, EC cells were capable of secreting circAURKB_288aa, influencing tumor microenvironmental cells similarly to full-length AURKB protein. Notably, AURKB siRNA targeting the shared kinase domain of both AURKB and circAURKB_288aa significantly inhibited EC malignancy. Collectively, these findings establish AURKB and circAURKB_288aa as promising targets for EC prognosis and therapy.

During this era of rapid advancements in cancer immunotherapy, the application of cell-released small vesicles that activate the immune system is of considerable interest. Exosomes are cell-derived nanovesicles that show great promise for the immunological treatment of cancer because of their immunogenicity and molecular transfer capacity. Recent technological advancements have enabled the identification of functional functions that exosome cargoes perform in controlling immune responses. Exosomes are originated specifically from immune cells and tumor cells and they show unique composition patterns directly related to the immunotherapy against cancer. Exosomes can also deliver their cargo to particular cells, which can affect the phenotypic and immune-regulatory functions of those cells. Exosomes can influence the course of cancer and have therapeutic benefits by taking part in several cellular processes; as a result, they have the dual properties of activating and restraining cancer. Exosomes have tremendous potential for cancer immunotherapy; they may develop into the most powerful cancer vaccines and carriers of targeted antigens and drugs. Comprehending the potential applications of exosomes in immune therapy is significant for regulating cancer progression. This review offers an analysis of the function of exosomes in immunotherapy, specifically as carriers that function as diagnostic indicators for immunological activation and trigger an anti-cancer immune response. Moreover, it summarizes the fundamental mechanism and possible therapeutic applications of exosome-based immunotherapy for human cancer.

Exosomes can regulate the malignant progression of tumors by carrying a variety of genetic information and transmitting it to target cells. Recent studies indicate that exosomal circular RNAs (circRNAs) regulate multiple biological processes in carcinogenesis, such as tumor growth, metastasis, epithelial-mesenchymal transition, drug resistance, autophagy, metabolism, angiogenesis, and immune escape. In the tumor microenvironment (TME), exosomal circRNAs can be transferred among tumor cells, endothelial cells, cancer-associated fibroblasts, immune cells, and microbiota, affecting tumor initiation and progression. Due to the high stability and widespread presence of exosomal circRNAs, they hold promise as biomarkers for tumor diagnosis and prognosis prediction in blood and urine. In addition, designing nanoparticles targeting exosomal circRNAs and utilizing exosomal circRNAs derived from immune cells or stem cells provide new strategies for cancer therapy. In this review, we examined the crucial role of exosomal circRNAs in regulating tumor-related signaling pathways and summarized the transmission of exosomal circRNAs between various types of cells and their impact on the TME. Finally, our review highlights the potential of exosomal circRNAs as diagnostic and prognostic prediction biomarkers, as well as suggesting new strategies for clinical therapy.

Ovarian cancer (OC) is the most common cause of death in female cancers. The prognosis of OC is very poor due to delayed diagnosis and identification of most patients in advanced stages, metastasis, recurrence, and resistance to chemotherapy. As chemotherapy with platinum-based drugs such as cisplatin (DDP) is the main treatment in most OC cases, resistance to DDP is an important obstacle to achieving satisfactory therapeutic efficacy. Consequently, knowing the different molecular mechanisms involved in resistance to DDP is necessary to achieve new therapeutic approaches. According to numerous recent studies, non-coding RNAs (ncRNAs) could regulate proliferation, differentiation, apoptosis, and chemoresistance in many cancers, including OC. Most of these ncRNAs are released by tumor cells into human fluid, allowing them to be used as tools for diagnosis. CircRNAs are ncRNA family members that have a role in the initiation, progression, and chemoresistance regulation of various cancers. In the current study, we investigated the roles of several circRNAs and their signaling pathways on OC progression and also on DDP resistance during chemotherapy.

Breast cancer remains the leading cause of cancer-related morbidity and mortality among women worldwide, underscoring the urgent need for novel diagnostic and therapeutic strategies. This review explores the emerging roles of circular RNAs (circRNAs) within extracellular vesicles (exosomes) in breast cancer. circRNAs, known for their stability and tissue-specific expression, are aberrantly expressed in breast cancer and regulate critical cellular processes such as proliferation, migration, and apoptosis, positioning them as promising biomarkers. Exosomes facilitate intercellular communication by delivering circRNAs, reflecting the physiological and pathological state of their source cells. This review highlights the multifaceted roles of exosomal circRNAs in promoting tumor growth, metastasis, and drug resistance through their modulation of tumor metabolism, the tumor microenvironment, and immune responses. In particular, we emphasize their contributions to chemotherapy resistance and their potential as both diagnostic markers and therapeutic targets. By synthesizing current research, this review provides novel insights into the clinical applications of exosomal circRNAs, offering a foundation for future studies aimed at improving breast cancer management through non-invasive diagnostics and targeted therapies.

Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.

Cancer cells exhibit altered metabolic pathways, prominently featuring enhanced glycolytic activity to sustain their rapid growth and proliferation. Dysregulation of glycolysis is a well-established hallmark of cancer and contributes to tumor progression and resistance to therapy. Increased glycolysis supplies the energy necessary for increased proliferation and creates an acidic milieu, which in turn encourages tumor cells' infiltration, metastasis, and chemoresistance. Circular RNAs (circRNAs) have emerged as pivotal players in diverse biological processes, including cancer development and metabolic reprogramming. The interplay between circRNAs and glycolysis is explored, illuminating how circRNAs regulate key glycolysis-associated genes and enzymes, thereby influencing tumor metabolic profiles. In this overview, we highlight the mechanisms by which circRNAs regulate glycolytic enzymes and modulate glycolysis. In addition, we discuss the clinical implications of dysregulated circRNAs in cancer glycolysis, including their potential use as diagnostic and prognostic biomarkers. All in all, in this overview, we provide the most recent findings on how circRNAs operate at the molecular level to control glycolysis in various types of cancer, including hepatocellular carcinoma (HCC), prostate cancer (PCa), colorectal cancer (CRC), cervical cancer (CC), glioma, non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer (GC). In conclusion, this review provides a comprehensive overview of the significance of circRNAs in cancer glycolysis, shedding light on their intricate roles in tumor development and presenting innovative therapeutic avenues.

Targeting non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), has recently emerged as a promising strategy for treating malignancies and other diseases. In recent years, the development of ncRNA-based therapeutics for targeting protein-coding and non-coding genes has also gained momentum. This review systematically examines ongoing and completed clinical trials to provide a comprehensive overview of the emerging landscape of ncRNA-based therapeutics. Significant efforts have been made to advance ncRNA therapeutics to early clinical studies. The most advanced trials have been conducted with small interfering RNAs (siRNAs), miRNA replacement using nanovector-entrapped miRNA mimics, or miRNA silencing by antisense oligonucleotides. While siRNA-based therapeutics have already received FDA approval, miRNA mimics, inhibitors, and lncRNA-based therapeutics are still under evaluation in preclinical and early clinical studies. We critically discuss the rationale and methodologies of ncRNA targeting strategies to illustrate this rapidly evolving field.

Since the first description of adenomyosis more than 150 years ago, multiple hypotheses have attempted to explain its pathogenesis. Indeed, research over recent years has greatly enhanced our knowledge of the underlying causes. This has opened up avenues for the development of strategies for both disease prevention and treatment of its main symptoms, such as pelvic pain, heavy menstrual bleeding, and infertility. However, the current means are still largely ineffective, so it is vital that we shed light on the pathways involved. Dysregulated mechanisms and aberrant protein expression have been identified as contributing factors in interactions between endometrial epithelial and stromal cells, ultimately leading to the growth of adenomyotic lesions. These include collective cell migration, epithelial-to-mesenchymal transition, hormonal influence, and signaling from non-coding RNAs and extracellular vesicles. We provide a concise summary of the latest insights into the crosstalk between glands and stroma in ectopic adenomyotic lesion formation. While there is an abundance of literature on similarities between adenomyosis and deep endometriosis, there are insufficient data on the cytochemical, molecular, and pathogenetic mechanisms of these two disorders. However, various shared features, including alterations of cell adhesion molecules, abnormal hormone regulation, and the presence of cancer-driving mutations and epigenetic modifications, have been identified. Nevertheless, the pathogenic mechanisms that contribute to the cause and development of these enigmatic diseases have not been fully elucidated yet.

Squamous cell carcinoma (SCC) is a prevalent malignancy affecting multiple organs in the human body, including the oral cavity, esophagus, cervix, and skin. Given its significant incidence and mortality rates, researchers are actively seeking effective diagnostic and therapeutic strategies. In recent years, exosomes and their molecular cargo, particularly circular RNA (circRNA), have emerged as promising areas of investigation in SCC research. Exosomes are small vesicles released into the extracellular environment by cells that contain biomolecules that reflect the physiological state of the cell of origin. CircRNAs, known for their unique covalently closed loop structure and stability, have garnered special attention in oncology and are closely associated with tumorigenesis, progression, metastasis, and drug resistance. Interestingly, exosomal circRNAs have been identified as ideal biomarkers for noninvasive cancer diagnosis and prognosis assessment. This article reviews the progress in research on exosomal circRNAs, focusing on their expression patterns, functions, and potential applications as biomarkers in SCC, aiming to provide new insights and strategies for the diagnosis and treatment of SCC.

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers.

Cervical cancer is a prominent cause of cancer-related mortality among women, with recent attention directed toward exploring the involvement of circular RNAs (circRNAs) in this particular cancer. CircRNAs, characterized by a covalently closed loop structure, belong to a class of single-stranded non-coding RNA (ncRNA) molecules that play crucial roles in cancer development and progression through diverse mechanisms. The abnormal expression of circRNAs in vivo is significantly associated with the development of cervical cancer. Notably, circRNAs actively interact with miRNAs in cervical cancer, leading to the regulation of diverse signaling pathways, and they can contribute to cancer hallmarks such as self-sufficiency in growth signals, insensitivity to antigrowth signals, limitless proliferation, evading apoptosis, tissue invasion and metastasis, and sustained angiogenesis. Moreover, the distinctive biomedical attributes exhibited by circRNAs, including their abundance, conservation, and stability in body fluids, position them as promising biomarkers for various cancers. In this review, we elucidate the tremendous potential of circRNAs as diagnostic markers or therapeutic targets in cervical cancer by expounding upon their biogenesis, characteristics, functions, and databases, highlighting the novel advances in the signaling pathways associated with circRNAs in cervical cancer.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality, with metastasis being the primary determinant of poor prognosis in patients. Investigating the molecular mechanisms underlying CRC metastasis is currently a prominent and challenging area of research. Exosomes, as crucial intercellular communication mediators, facilitate the transfer of metabolic and genetic information from cells of origin to recipient cells. Their roles in mediating information exchange between CRC cells and immune cells, fibroblasts, and other cell types are pivotal in reshaping the tumor microenvironment, regulating key biological processes such as invasion, migration, and formation of pre-metastatic niche. This article comprehensively examines the communication function and mechanism of exosomes derived from different cells in cancer metastasis, while also presenting an outlook on current research advancements and future application prospects. The aim is to offer a distinctive perspective that contributes to accurate diagnosis and rational treatment strategies for CRC.

Circular RNAs (circRNAs) have been recognized as key components in the intricate regulatory network of the KRAS pathway across various cancers. The KRAS pathway, a central signalling cascade crucial in tumorigenesis, has gained substantial emphasis as a possible therapeutic target. CircRNAs, a subgroup of non-coding RNAs known for their closed circular arrangement, play diverse roles in gene regulation, contributing to the intricate landscape of cancer biology. This review consolidates existing knowledge on circRNAs within the framework of the KRAS pathway, emphasizing their multifaceted functions in cancer progression. Notable circRNAs, such as Circ_GLG1 and circITGA7, have been identified as pivotal regulators in colorectal cancer (CRC), influencing KRAS expression and the Ras signaling pathway. Aside from their significance in gene regulation, circRNAs contribute to immune evasion, apoptosis, and drug tolerance within KRAS-driven cancers, adding complexity to the intricate interplay. While our comprehension of circRNAs in the KRAS pathway is evolving, challenges such as the diverse landscape of KRAS mutant tumors and the necessity for synergistic combination therapies persist. Integrating cutting-edge technologies, including deep learning-based prediction methods, holds the potential for unveiling disease-associated circRNAs and identifying novel therapeutic targets. Sustained research efforts are crucial to comprehensively unravel the molecular mechanisms governing the intricate interplay between circRNAs and the KRAS pathway, offering insights that could potentially revolutionize cancer diagnostics and treatment strategies.

Gastrointestinal cancer is frequently detected at an advanced stage and has an undesirable prognosis due to the absence of efficient and precise biomarkers and therapeutic targets. Exosomes are small, living‑cell‑derived vesicles that serve a critical role in facilitating intercellular communication by transporting molecules from donor cells to receiver cells. circular RNAs (circRNAs) are mis‑expressed in a variety of diseases, including gastrointestinal cancer, and are promising as diagnostic biomarkers and tumor therapeutic targets for gastrointestinal cancer. The main features of exosomes and circRNAs are discussed in the present review, along with research on the biological function of exosomal circRNAs in the development and progression of gastrointestinal cancer. It also assesses the advantages and disadvantages of implementing these findings in clinical applications.

Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial-mesenchymal transition (EMT) and mesothelial-mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

Exosomes are nano-scale extracellular vesicles that are found widely in various biological fluids. As messengers, exosomes deliver characteristic biological information from donor cells, facilitating their accumulation and subsequent transfer of information to tumor immune cells. Immunotherapy is a cutting-edge strategy for cancer therapy, but it has not yet reached its full potential owing to severe side effects and limited efficacy. Exosomes possess antigens and immunostimulatory molecules and can serve as cell-free vaccines to induce antitumor immunity. In addition, given their stability, low immunogenicity, and targeting ability, exosomes represent ideal drug delivery systems in tumor immunotherapy by delivering cargoes, including non-coding ribonucleic acids (RNAs), membrane proteins, chemotherapeutic agents, and immune cell death inducers. Exosomes can also be engineered to precisely target tumor cells. However, as a rising star in tumor immunotherapy, exosomes are also impeded by some challenges, including the lack of uniform technical standards for their isolation and purification, the need to improve exosomal cargo loading for efficient exosome delivery, and the expansion of clinical trials, which are currently in their infancy. Long-term, multi-center, and large-scale clinical trials are needed to evaluate the performance of exosomes in the future. Nonetheless, exosomes have demonstrated encouraging performance in tumor immunotherapy. In this review, we summarize the potential and challenges of exosomes in tumor immunotherapy, with the aim to shed light on exosomes as new-era tumor immunotherapy tools.

Alzheimer's disease (AD) is the most common form of dementia that affects millions of individuals worldwide. Although the research over the last decades has provided new insight into AD pathophysiology, there is currently no cure for the disease. AD is often only diagnosed once the symptoms have become prominent, particularly in the late-onset (sporadic) form of AD. Consequently, it is essential to further new avenues for early diagnosis. With recent advances in genomic analysis and a lower cost of use, the exploration of genetic markers alongside RNA molecules can offer a key avenue for early diagnosis. We have here provided a brief overview of potential genetic markers differentially expressed in peripheral tissues in AD cases compared to controls, as well as considering the changes to the dynamics of RNA molecules. By integrating both genotype and RNA changes reported in AD, biomarker profiling can be key for developing reliable AD diagnostic tools.