RNA-binding proteins (RBPs) regulate the generation of circular RNAs (circRNAs) by participating in the reverse splicing of circRNA and thereby influencing circRNA function in cells and diseases, including cancer. Increasing evidence has demonstrated that the circRNA-RBP network plays a complex and multifaceted role in tumor progression. Thus, a better understanding of this network may provide new insights for the discovery of cancer drugs. In this review, we discuss the characteristics of RBPs and circRNAs and how the circRNA-RBP network regulates tumor cell phenotypes such as proliferation, metastasis, apoptosis, metabolism, immunity, drug resistance, and the tumor environment. Moreover, we investigate the factors that influence circRNA-RBP interactions and the regulation of downstream pathways related to tumor development, such as the tumor microenvironment and N6-methyladenosine modification. Furthermore, we discuss new ideas for targeting circRNA-RBP interactions using various RNA technologies.

Gastric cancer (GC) poses a major global health challenge, underscoring the need for advanced diagnostic and therapeutic approaches. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators in GC, with their dysregulated expression driving key processes such as tumorigenesis, metastasis, immune evasion, and chemoresistance. The functional diversity of ncRNAs across different GC molecular subtypes highlights their potential as biomarkers for improved subtype classification and patient stratification. Beyond their diagnostic value, ncRNAs demonstrate critical regulatory functions in tumor biology, establishing these RNA molecules as promising targets for therapeutic development. Strategies based on RNA hold considerable promise for addressing critical challenges such as immune escape and drug resistance by modulating key signaling pathways. These approaches can enhance immune responses, reprogram the tumor microenvironment, and reverse resistance mechanisms that compromise treatment efficacy, thereby improving clinical outcomes. Although ncRNAs represent a promising frontier in GC precision medicine, further research is required to fully harness their clinical potential.

Dysregulation of cytokine signaling is central to the development and progression of cancer. Cytokines are not only involved in promoting cancer development but also regulate anti-tumor immune responses. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules lacking free ends, which have emerged as critical regulators of cytokine signaling. Transcriptional and post-transcriptional regulation of cytokine signaling by circRNAs contributes to cancer pathogenesis. Here, we discuss the emerging role of circRNAs in modulating cytokine signaling pathways that regulate cancer development. In particular, we examine the role of circRNAs in TGF-β, IL-6, IL-10, TNF-α, VEGF, FGF, PDGF, and chemokine signaling in cancer.

The tumor microenvironment (TME) plays a crucial role in the development and progression of gastric cancer (GC). The TME comprises a network of cancer cells, immune cells, fibroblasts, endothelial cells, and extracellular matrix components, which provide a supportive niche for cancer cells. This study investigates the role of TME-derived exosomal competitive endogenous RNAs (ceRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as major regulating agents in GC development. Exosomal ceRNAs control gene expression across several TME components, amplifying cancer hallmarks like cell proliferation, invasion, metastases, and chemoresistance. They promote dynamic interplay between cancer cells and adjacent stromal cells, enabling tumor development through immune suppression, angiogenesis, and epithelial-mesenchymal transition (EMT). Exosomal ceRNAs can modify the TME, creating a pro-tumorigenic milieu and preparing cancer cells to avoid immunological responses, defy death, and adapt to therapeutic pressures. This review highlights the understudied interactions between the TME and exosomal ceRNAs in gastric cancer and emphasizes their potential utility as diagnostic and therapeutic tools.

Previous studies conducted by the same group of researchers found that Traditional Chinese Medicine Astragalus mongholicus Bunge and Hedyotis diffusa Willd (A-H) significantly suppressed the cell proliferation of lung adenocarcinoma (LUAD). MicroRNAs are considered promising candidates for cancer diagnosis and treatment. This study focused on miR-582-3p as the primary subject of investigation to explore the mechanism by which A-H inhibits cell proliferation through miR-582-3p. The overexpressing and silencing miR-582-3p cell models were established by using lentiviral transfection technology. CCK-8 assay (24 h, 48 h, 72 h) and clone formation assay (1 w) were employed to detect the proliferation of A549 cells. Moreover, flow cytometry analysis (24 h) was performed to detect the cell cycle. Western blotting (WB) and a luciferase reporter assay were also used to measure the expression of cell cycle-related proteins and verify the direct interaction between miR-582-3p and p27, respectively. The LV-miR-582-3p inhibitor + shRNA-p27 stable A549 cells were constructed in the same manner to repeat the above-mentioned procedure. The CCK-8 assay was conducted to assess the effects of various concentrations of A-H on the proliferation of A549 cells. A-H-containing serum was prepared to intervene in LV-miR-582-3p and mimic A549 cells. Subsequently, the same procedure was repeated, as described earlier. Results indicated a direct interaction between miR-582-3p and p27. Furthermore, miR-582-3p was found to enhance the proliferation of A549 cells by regulating cell cycle-related proteins, specifically p27. It was also observed that A-H-containing serum inhibited the proliferation of A549 cells through the miR-582-3p-p27 signaling pathway. The study findings revealed the underlying molecular mechanisms of miR-582-3p in the development and prognosis of A549 LUAD cells. In addition, A-H inhibited LUAD proliferation through the miR-582-3p-p27 signaling pathway. These findings may provide a new understanding of the use of Chinese medicine in treating lung cancer.

One of the most prevalent malignant tumors worldwide, stomach cancer still has a high incidence and fatality rate in China, and the number of young people developing early-onset gastric cancer is steadily increasing. The 5-year survival rate of stomach cancer is typically 30%-35%, the prognosis is bad, the patients' quality of life is low, and the progression of advanced gastric cancer cannot be effectively managed despite the use of surgical surgery, chemotherapy, and other medicines. We urgently need molecular biomarkers with high specificity and sensitivity to increase the early gastric cancer detection rate, extend patient survival, and improve patient quality of life. The initial diagnosis of gastric cancer primarily depends on gastroscopy and biopsy, and invasive procedures cause significant discomfort to patients. Similar to this, treating advanced and metastatic stomach cancer is a pressing issue that requires attention. More and more immune checkpoint molecules have been discovered, and corresponding inhibitors are gradually being applied to clinical diagnosis and treatment. Recently, some non-coding RNAs have begun to be used as new targets for the treatment of gastric cancer. Some non-coding RNAs are highly present in the serum or urine of gastric cancer patients and can be used as diagnostic markers or prognostic indicators. Many clinical trials targeting non-coding RNAs have also shown good therapeutic effects. In general, targeting non-coding RNAs has shown good therapeutic effects. The biomarkers for gastric cancer detection and treatment are reviewed in this article, focusing on the new non-coding RNAs used in diagnosis, prognosis, and treatment. Patients with stomach cancer should have access to more precise and efficient diagnosis and treatment choices as a result of ongoing technological advancements and thorough research.

Gastrointestinal (GI) cancers, which predominantly manifest in the stomach, colorectum, liver, esophagus, and pancreas, accounting for approximately 35% of global cancer-related mortality. The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers. This non-invasive technique not only facilitates prompt therapeutic intervention, but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence. The wealth of circulating exosomes present in body fluids is often enriched with proteins, lipids, microRNAs, and other RNAs derived from tumor cells. These specific cargo components are reflective of processes involved in GI tumorigenesis, tumor progression, and response to treatment. As such, they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer. In this review, we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles. We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application. Furthermore, we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.

Acquired drug resistance is a main factor contributing to cancer therapy failure and high cancer mortality, highlighting the necessity to develop novel intervention targets. Circular RNAs (circRNAs), an abundant class of RNA molecules with a closed loop structure, possess characteristics including high stability, which provide unique advantages in clinical application. Growing evidence indicates that aberrantly expressed circRNAs are associated with resistance against various cancer treatments, including targeted therapy, chemotherapy, radiotherapy, and immunotherapy. Therefore, targeting these aberrant circRNAs may offer a strategy to improve the efficiency of cancer therapy. Herein, we present a summary of the most recently studied circRNAs and their regulatory roles on cancer drug resistance. With the advances in artificial intelligence (AI)-based bioinformatics algorithms, circRNAs could emerge as promising biomarkers and intervention targets in cancer therapy.

Circular RNAs (circRNAs) are a large family of non-coding RNAs characterized by a single-stranded, covalently closed structure, predominantly synthesized through a back-splicing mechanism. While thousands of circRNAs have been identified, only a few have been functionally characterized. Although circRNAs are less abundant than other RNA types, they exhibit exceptional stability due to their covalently closed structure and demonstrate high cell and tissue specificity. CircRNAs play a critical role in maintaining cellular homeostasis by influencing gene transcription, translation, and post-translation processes, modulating the immune system, and interacting with mRNA, miRNA, and proteins. Abnormal circRNA expression has been associated with a wide range of human diseases and various infections. Due to their remarkable stability in body fluids and tissues, emerging research suggests that circRNAs could serve as diagnostic and therapeutic biomarkers for these diseases. This review focuses on the emerging role of circRNAs in various human diseases, exploring their biogenesis, molecular functions, and potential clinical applications as diagnostic and therapeutic biomarkers with current evidence, challenges, and future perspectives. The key theme highlights the significance of circRNAs in regulating gene expression, their involvement in diseases like cancer, neurodegenerative disorders, cardiovascular diseases, and diabetes, and their potential use in translational medicine for developing novel therapeutic strategies. We also discuss recent clinical trials involving circRNAs. Thus, this review is important for both basic researchers and clinical scientists, as it provides updated insights into the role of circRNAs in human diseases, aiding further exploration and advancements in the field.

Small extracellular vesicles (sEVs) play a critical role in the progression, diagnosis, and treatment of prostate cancer (PCa), particularly within the tumor microenvironment (TME). Acting as novel biomarkers and agents for targeted biological therapy, sEVs contribute significantly to improving patient survival. These vesicles transport a variety of biomolecules, including proteins, nucleic acids, and lipids, which are instrumental in remodeling the TME, facilitating intercellular communication, and influencing key processes such as tumor growth, metastasis, and therapy resistance. A thorough understanding of sEV heterogeneity, including their biogenesis, characteristics, and potential applications, is essential. Recent advances have illuminated the origins, formation processes, and molecular cargo of PCa-derived sEVs (PCa-sEVs), enhancing our understanding of their role in disease progression. Furthermore, sEVs show promise as diagnostic markers, with potential applications in early detection and prognostic assessment in PCa. Therapeutically, natural and engineered sEVs offer versatile applications, including drug delivery, gene therapy, and immunomodulation, underscoring their potential in PCa management. This review delves into the substantial potential of sEVs in clinical practices for PCa.

Gastric cancer (GC) is one of the most common gastrointestinal cancers worldwide, with consistently high morbidity and mortality rates and poor prognosis. Most patients are diagnosed at an advanced stage due to the lack of specific presentation in the early stages. Exosomes are a class of extracellular vesicles (EVs) widely found in body fluids and can release genetic material or multiple proteins to facilitate intercellular communication. In recent years, exosomal miRNAs have gained attention for their role in various cancers. These exosomal miRNAs can impact GC development and progression by targeting specific genes or influencing signaling pathways and cytokines involved in Angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and immune regulation. They show great potential in terms of diagnosis, prognosis, and treatment of GC. Notably, the gastrointestinal tract has the largest number of macrophages, which play a significant role in GC progression. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and can influence macrophage programming through various mediators, including macrophage polarization. Macrophage polarization is involved in inflammatory responses and significantly impacts the GC process.

Circular RNAs (circRNAs) are formed by splicing of precursor RNAs and covalently linked at the 5' and 3' ends. Dysregulated circRNAs are closely related to the epithelial-mesenchymal transition (EMT) of gastrointestinal malignancies. CircRNAs, including circRNA_0008717, circGOT1, circ-DOCK5, circVPS33B, circPVT1, circMET, circ-OXCT1, circ_67835, circRTN4, circ_0087502, circFNDC38, circ_PTEN1, circPGPEP1, and circ-E-Cad are involved in the EMT process of gastrointestinal malignancies through a variety of mechanisms, such as regulating EMT-inducing transcription factors, signaling pathways, and tumor microenvironments. Gastrointestinal (GI) malignancies are common malignant tumors worldwide, and the heterogeneity and easy metastasis of gastrointestinal malignancies limit the effectiveness of medical treatments. Therefore, investigating the molecular mechanisms involved in the pathogenesis of gastrointestinal malignancies is essential for clinical treatment. This article summarizes the biological roles and molecular mechanism of circRNAs in EMT of gastrointestinal malignancies, providing a theoretical basis for applying EMT-related circRNAs in targeted therapy.

Gastric cancer (GC) is a common and frequent malignant cancer of the digestive system with a poor prognosis. In addition to common therapies such as surgical resection and chemotherapy, novel biological interventions are quite valuable for research. Exosomes are extracellular vesicles (EVs) that originate from various cell types and contain proteins, RNA, DNA, and other components that transmit biological signals and mediate intercellular communication. Numerous studies have shown that exosomes shape the tumor microenvironment (TME) by affecting hypoxia, inflammation, immunity, metabolism, and interstitial changes in the tumor, playing a crucial role in the development and metastasis of GC. This article reviews the important role of exosomes in the TME of GC and explores their potential clinical applications in GC treatment.

This review explores the critical role of exosomes in promoting angiogenesis, a key factor in skin flap survival. Skin flaps are widely used in reconstructive surgery, and their survival depends heavily on the formation of new blood vessels. Exosomes, small extracellular vesicles secreted by various cells, have emerged as important mediators of intercellular communication and play a crucial role in biological processes such as angiogenesis. Compared to traditional methods of promoting angiogenesis, exosomes show more selective and targeted therapeutic potential as they naturally carry angiogenic factors and can precisely regulate the angiogenesis process. The review will delve into the molecular mechanisms by which exosomes facilitate angiogenesis, discuss their potential therapeutic applications in enhancing skin flap survival, and explore future research directions, particularly the challenges and prospects of exosomes in clinical translation. By highlighting the unique advantages of exosomes in skin flap survival, this review provides a new perspective in this field and opens up new research directions for future therapeutic strategies.

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.

Pancreatic adenocarcinoma (PAAD) is a fatal disease with poor survival. Increasing evidence show that hypoxia-induced exosomes are associated with cancer progression. Here, we aimed to investigate the function of hsa_circ_0007678 (circR3HCC1L) and hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD progression. Through the exoRBase 2.0 database, we screened for a circular RNA circR3HCC1L related to PAAD. Changes of circR3HCC1L in PAAD samples and cells were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion were analyzed by colony formation, cell counting, and transwell assays. Measurements of glucose uptake and lactate production were done using corresponding kits. Several protein levels were detected by western blotting. The regulation mechanism of circR3HCC1L was verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Exosomes were separated by differential ultracentrifugation. Animal experiments were used to verify the function of hypoxia-derived exosomal circR3HCC1L. CircR3HCC1L was upregulated in PAAD samples and hypoxic PAAD cells. Knockdown of circR3HCC1L decreased hypoxia-driven PAAD cell proliferation, migration, invasion, and glycolysis. Hypoxic PAAD cell-derived exosomes had higher levels of circR3HCC1L, hypoxic PAAD cell-derived exosomal circR3HCC1L promoted normoxic cancer cell malignant transformation and glycolysis in vitro and xenograft tumor growth in mouse models in vivo. Mechanistically, circR3HCC1L regulated pyruvate kinase M2 (PKM2) expression via sponging miR-873-5p. Also, PKM2 overexpression or miR-873-5p silencing offset circR3HCC1L knockdown-mediated effects on hypoxia-challenged PAAD cell malignant transformation and glycolysis. Hypoxic PAAD cell-derived exosomal circR3HCC1L facilitated PAAD progression through the miR-873-5p/PKM2 axis, highlighting the contribution of hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD.

Gastric cancer (GC) remains a prevalent and preventable disease, yet accurate early diagnostic methods are lacking. Exosome non-coding RNAs (ncRNAs), a type of liquid biopsy, have emerged as promising diagnostic biomarkers for various tumours. This study aimed to identify a serum exosome ncRNA feature for enhancing GC diagnosis.

Serum exosomes from patients with GC (n=37) and healthy donors (n=20) were characterised using RNA sequencing, and potential biomarkers for GC were validated through quantitative reverse transcription PCR (qRT-PCR) in both serum exosomes and tissues. A combined diagnostic model was developed using LASSO-logistic regression based on a cohort of 518 GC patients and 460 healthy donors, and its diagnostic performance was evaluated via receiver operating characteristic curves.

RNA sequencing identified 182 candidate biomarkers for GC, of which 31 were validated as potential biomarkers by qRT-PCR. The combined diagnostic score (cd-score), derived from the expression levels of four long ncRNAs (RP11.443C10.1, CTD-2339L15.3, LINC00567 and DiGeorge syndrome critical region gene (DGCR9)), was found to surpass commonly used biomarkers, such as carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and CA72-4, in distinguishing GC patients from healthy donors across training, testing and external validation cohorts, with AUC values of 0.959, 0.942 and 0.949, respectively. Additionally, the cd-score could effectively identify GC patients with negative gastrointestinal tumour biomarkers and those in early-stage. Furthermore, molecular biological assays revealed that knockdown of DGCR9 inhibited GC tumour growth.

Our proposed serum exosome ncRNA feature provides a promising liquid biopsy approach for enhancing the early diagnosis of GC.

Exosome-delivered circular RNAs (circRNAs) are recognized as a key mechanism that regulates osteosarcoma (OS) progression. The purpose of this study is to discover the role of a novel circRNA hsa_circ_0000116 from exosomes in OS progression. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were used to identify the exosomes isolated from two OS cell lines (HOS and MG-63). After coculturing exosomes with OS cells and transfecting hsa_circ_0000116 knockdown vector into OS cells, cell function experiments, including cell counting kit-8, wound healing, and Transwell experiments, were performed to assess the change of OS cell malignant phenotype. In addition, the levels of PI3K/Akt/mTOR and p38/MAPK pathways-associated proteins were measured using western blotting. Exosomes with around 100 nm in diameter were successfully isolated from HOS and MG-63 cells, and promote OS cells to proliferate, migrate, and invade. hsa_circ_0000116 was upregulated in OS-derived exosomes, and silencing hsa_circ_0000116 declined the exosome-induced OS cell malignancy. In addition, inhibiting hsa_circ_0000116 effectively inhibited exosome-mediated activation of PI3K/Akt/mTOR and p38/MAPK pathways. In conclusion, exosomal hsa_circ_0000116 can facilitate OS cell malignancy by inducing the activation of PI3K/Akt/mTOR and p38/MAPK pathways. The findings of this study may identify novel molecular mechanisms driving OS progression and provide novel therapeutic targets for OS.

Circular RNAs (circRNAs) are a class of noncoding RNAs that lack the 5'-cap structure and the 3' poly(A) tail. Their distinguishing feature is that the 3' and 5' ends are covalently linked to form a closed circular structure. CircRNAs have a longer half-life and stronger ribonuclease resistance compared with linear RNA. Viral infections lead to the production of circRNA molecules through the transcription and splicing mechanisms of host cells. circRNAs are produced from the transcription and splicing of the viral genome or from the splicing reactions of the host cell gene. They participate in regulating the replication of many viruses, including coronaviruses, human herpesviruses, human immunodeficiency virus, and cytomegalovirus. CircRNAs regulate the infection process by modulating circRNA expression in host cells and affect cellular biological processes. Some circRNAs have been proposed as diagnostic markers for viral infections. In this review, we discussed the properties of virus-derived circRNAs, the biological functions of diverse viruses-derived and host circRNAs during viral infections, and the critical role of circRNAs in the host's antiviral immune defense. Extensive research on the applications of circRNAs can help us better understand gene regulatory networks and disease mechanisms.

Stomach cancer is considered the fifth most common cancer worldwide. This study utilized bibliometric analysis to construct a visualization map of the relationship between stomach cancer and exosomes, aiming to reveal research trends and emerging themes, and provide direction for future research.

Retrieve relevant literature on gastric cancer exosomes in the Web of Science Core Collection (WoSCC) over the past 25 years according to search criteria, and conduct bibliometric and visualization analysis using bibliometric software VOSviewer and CiteSpace.

This study included a total of 727 articles, with an overall increasing trend in annual publication output. There were 68 countries involved, with China having the largest number of publications followed by the United States. A total of 957 research institutions were involved, with most of the top 10 institutions in terms of publication output being universities in China. The top 5 journals are Molecular Cancer, Cell death & disease, Cancers, International journal of molecular sciences, and Frontiers in oncology. A total of 4529 authors were involved, with 5 authors having a publication output of no less than 13 articles. A total of 35516 references were cited, with a total number of citations. The top publication is "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells".

Over the past 25 years, researchers have been dedicated to studying the field of exosomes related to gastric cancer, and research in this area is currently progressing steadily. Based on previous studies, exosomes in gastric adenocarcinoma serve as biomarkers, potential therapeutic targets, and post-resistance treatment, which represents current hotspots and emerging frontiers in research.

Circular RNAs (circRNAs) are identified as a novel family of endogenous RNA molecules through 'back-splicing' and covalently linked at the 5' and 3' ends. Emerging researches have demonstrated circRNAs are stable and abundant in exosomes called exosomal circRNAs (exo-circRNA).

We searched recent studies and references to summary the research progress of exosomal circRNA.

Recent studies have revealed that exosome-derived circRNAs including exo-CDR1as, exo-circRanGAP1, exo-circIAR play vital roles in cell proliferation and apoptosis, epithelial mesenchymal transition, invasion and metastasis, angiogenesis, immune evasion, cellular crosstalk, cancer cachexia through a variety of biological mechanisms, such as serving as microRNA sponges, interacting with RNA binding proteins, regulating gene transcription, N6-Methyladenosine modification and so on. Due to their characteristics of origin, structure, properties and biological functions, exo-circRNAs are expected to apply in precious diagnosis and prognostic indicators, improving drug and radiation resistance and sensitivity, becoming biological therapeutic targets.

We summarize the update of digestive malignancies associated exo-circRNAs in biogenesis, biological functions, molecular mechanisms, clinical implications, potential applications and experimental technique in order to effectively promote transformation and application in the future.

Gastric cancer (GC) is a global health concern, contributing significantly to cancer-related mortality rates. Early detection is vital for improving patient outcomes. Recently, circular RNAs (circRNAs) have emerged as crucial players in the development and progression of various cancers, including GC.

This comprehensive review underscores the promising potential of circRNAs as innovative biomarkers for the early diagnosis of GC, as well as their possible utility as therapeutic targets for this life-threatening disease. Specifically, the review focuses on recent findings, mechanistic insights, and clinical applications of circRNAs in GC.

Dysregulation of circRNAs has been consistently observed in GC tissues, offering potential diagnostic value due to their stability in bodily fluids such as blood and urine. For instance, circPTPN22 and hsa_circ_000200. Furthermore, the expression levels of circRNAs such as circCUL2, hsa_circ_0000705 and circSHKBP1 have shown strong associations with critical clinical features of GC, including diagnosis, prognosis, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) stage, and treatment response. Additionally, circRNAs such as circBGN, circLMO7, and circMAP7D1 have shown interactions with specific microRNAs (miRNAs), proteins, and other molecules that play key roles in development and progression of GC. This further highlighting their potential as therapeutic targets. Despite their potential, several challenges need to be addressed to effectively apply circRNAs as GC biomarkers. These include standardizing detection methods, establishing cutoff values for diagnostic accuracy, and validating findings in larger patient cohorts. Moreover, the functional mechanisms by which circRNAs contribute to GC pathogenesis and therapeutic resistance warrant further investigation. Advances in circRNAs research could provide valuable insights into the early detection and targeted treatment of GC, ultimately improving patient outcomes.

Circular RNAs have been implicated as critical regulators in the initiation and progression of colorectal cancer (CRC). This study was intended to elucidate the functional significance of the circ_0089761/miR-27b-3p/programmed cell death ligand 1 (PD-L1) axis in CRC. Our findings indicated that circ_0089761 expression was significantly elevated in CRC tissues and cell lines. Furthermore, the high expression of circ_0089761 was correlated with TNM stage and tumor size. Silencing circ_0089761 inhibited CRC cell proliferation, migration, and invasion, and increased apoptosis. Mechanistically, circ_0089761 facilitated its biological function by binding to miR-27b-3p to upregulate PD-L1 expression in CRC. Coculture experiments confirmed that low expression of circ_0089761 impeded CD8 + T cell apoptosis and depletion, activated CD8 + T cell function, and increased secretion of the immune effector cytokines IFN-γ, TNF-α, perforin, and granzyme-B. MiR-27b-3p inhibition or PD-L1 overexpression partially impeded CD8 + T cell function. The circ_0089761/miR-27b-3p/PD-L1 axis is postulated to exert pivotal functions in the mechanistic progression of CRC. Furthermore, it holds promising prospects as a feasible biomarker and therapeutic target for CRC.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs with covalently closed structures formed by reverse splicing of precursor mRNAs. The widespread expression of circRNAs across species has been revealed by high-throughput sequencing and bioinformatics approaches, indicating their unique properties and diverse functions including acting as microRNA sponges and interacting with RNA-binding proteins. Programmed cell death (PCD), encompassing various forms such as apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis, is an essential process for maintaining normal development and homeostasis in the human body by eliminating damaged, infected, and aging cells. Many studies have demonstrated that circRNAs play crucial roles in tumourigenesis and development by regulating PCD in tumor cells, showing that circRNAs have the potential to be biomarkers and therapeutic targets in cancer. This review aims to comprehensively summarize the intricate associations between circRNAs and diverse PCD pathways in tumor cells, which play crucial roles in cancer development. Additionally, this review provides a detailed overview of the underlying mechanisms by which circRNAs modulate various forms of PCD for the first time. The ultimate objective is to offer valuable insights into the potential clinical significance of developing novel strategies based on circRNAs and PCD for cancer diagnosis, prognosis, and treatment.

RNA binding proteins (RBPs) play a role in sorting non-coding RNAs (ncRNAs) into exosomes. These ncRNAs, carried by exosomes, are involved in regulating various aspects of tumor progression, including metastasis, angiogenesis, control of the tumor microenvironment, and drug resistance. Recent studies have emphasized the importance of the RBP-ncRNA-exosome mechanism in tumor regulation.

This comprehensive review aims to explore the RBP-ncRNA-exosome mechanism and its influence on tumor development. By understanding this intricate mechanism provides novel insights into tumor regulation and may lead to innovative treatment strategies in the future.

The review discusses the formation of exosomes and the complex relationships among RBPs, ncRNAs, and exosomes. The RBP-ncRNA-exosome mechanism is shown to affect various aspects of tumor biology, including metastasis, multidrug resistance, angiogenesis, the immunosuppressive microenvironment, and tumor progression. Tumor development relies on the transmission of information between cells, with RBPs selectively mediating sorting of ncRNAs into exosomes through various mechanisms, which in turn carry ncRNAs to regulate RBPs. The review also provides an overview of potential therapeutic strategies, such as targeted drug discovery and genetic engineering for modifying therapeutic exosomes, which hold great promise for improving cancer treatment.

Extracellular vesicles (EVs) have emerged as valuable biomarkers in liquid biopsies owing to their stability, accessibility, and ability to encapsulate nucleic acids. The majority of existing methodologies for detecting EV nucleic acid biomarkers require the lysis of EVs to extract DNA or RNA. This process is labor-intensive and may lead to the loss and degradation of nucleic acids. However, the emerging field of in situ EV assays offers innovative tools for liquid biopsy, facilitating direct profiling of nucleic acids within intact EVs and reducing sample handling procedures. This review focuses on the promising and innovative field of in situ EV nucleic acid analysis. It examines the translational potential of in situ EV nucleic acid analysis in liquid biopsies from detection strategies, diagnostic applications, and diagnostic aids for single EV analysis and machine learning techniques. We highlight the innovative approach of in situ EV nucleic acid assays and provide novel insights into advancing liquid biopsy technology. This approach shows a promising avenue for improving EV-based cancer diagnosis and guiding personalized treatment with minimal invasiveness.

Lung cancer stands out as a leading cause of death among various cancer types, highlighting the urgent need for effective anticancer drugs and the discovery of new compounds with potent therapeutic properties. Natural sources, such as the Conamomum genus, offer various bioactive compounds. Adunctin E (AE), a dihydrochalcone derived from Conamomum rubidum, exhibited several pharmacological activities, and its potential as an anticancer agent remains largely unexplored. Thus, this study aimed to elucidate its apoptotic-inducing effect and identify its molecular targets. The network pharmacology analysis led to the identification of 71 potential targets of AE against lung cancer. Subsequent gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway enrichment analyses revealed the involvement of these targets in cancer-associated signaling pathways. Notably, HSP90AA1, MAPK1, and PIK3CA emerged as key players in apoptosis. In silico molecular docking and dynamic simulations suggested a strong and stable interaction between AE and HSP90AA1. In vitro experiments further confirmed a significant apoptotic-inducing effect of AE on lung cancer cell lines A549 and H460. Furthermore, immunoblot analysis exhibited a substantial decrease in HSP90AA1 levels in response to AE treatment. These findings support the potential anticancer activity of AE through the HSP90AA1 mechanism, underscoring its promise as a novel compound worthy of further research and development for anti-lung cancer therapy.

Papillary thyroid carcinoma (PTC) involves complex genetic mechanisms, notably involving CLDN1 and EGFR. This study investigates the expression and variations of these genes and their effects on tumor behavior and patient outcomes. Meta-analysis of CLDN1 and EGFR expression in TCGA-PTC patients and GEO datasets was conducted. cBioPortal was used for clinical analysis. GSEA, GO, KEGG, Hallmark pathways, and cibersort analysis were applied. Cell proliferation, migration, invasion, and apoptosis were assessed in vitro. Co-culturing with CD8+ T cells, MTT assay, ELISA, subcutaneous tumor models, and immunohistochemistry were performed. TGF-β pathway-related proteins were analyzed via Western blot. CLDN1 and EGFR were overexpressed in PTC tumors, correlating with higher-risk patients and reduced CD8+ T cell infiltration. Silencing these genes inhibited tumor cell functions and enhanced CD8+ T cell activity, both in vitro and in vivo. CLDN1 and EGFR are crucial in PTC, linked to tumor invasiveness, EMT, and immune suppression, presenting them as potential therapeutic targets.

Aim: To explore precise function and underlying mechanism of circ_0006988 in gastric cancer (GC).Materials & methods: GC tissues were collected clinically, and GC cells were purchased from the company. Quantitative real-time polymerase chain reaction and western blot were used to detect mRNA and protein expression. Functional analysis was performed through CCK-8, Transwell and scratch experiment. Binding relationship was validated through dual luciferase reporter and RNA immunoprecipitation assays. HGC-27 cells were subcutaneously injected into mice to construct a xenograft tumor model.Results: In GC tissues and cells, circ_0006988 overexpressed, promoting proliferation, migration and invasion. MiRNA-92a-2-5p downregulation or TFAP4 overexpression weakened effects of circ_0006988 silencing on GC progression.Conclusion: circ_0006988 facilitates GC development through miRNA-92a-2-5p/TFAP4 axis.

Persistent macrophage activation and cytokine storms are critical causes for the rapid disease progression and high mortality rate of Secondary Hemophagocytic lymphohistiocytosis (sHLH). Identification of key regulatory factors that govern the activation of macrophages is vital. Plasma exosomal circular RNAs (circRNAs) are considered important biomarkers and potential therapeutic targets for various diseases, however, their function in sHLH is still unclear. In this study, we demonstrated for the first time that circMETTL3, derived from METTL3, is upregulated in sHLH patient plasma exosomes, which may plays an important role in the diagnosis of sHLH. Significantly, we also revealed that a novel peptide encoded by circMETTL3, METTL3-156aa, is an inducer of M1 macrophage polarization, which is responsible for the development of cytokine storms during sHLH. We then identified that METTL3-156aa binding with lactate dehydrogenase A (LDHA) and promotes M1 macrophage polarization by enhancing macrophage glycolysis. Additionally, the glycolysis metabolite lactate upregulates the cleavage factor SRSF10 expression by lactylation. This results in increased splicing of the pre-METTL3 mRNA, leading to an enchance in the production of cirMETTL3. Therefore, our results suggest that the circMETTL3/METTL3-156aa/LDHA/Lactate/SRSF10 axis forms a positive feedback loop and may be a novel therapeutic target for the treatment of sHLH.

One of the most prevalent pathological types of Primary Liver Cancer (PLC) is the Hepatocellular Carcinoma (HCC) poses a global health issue. The high recurrence and metastasis rate of HCC, coupled with a low 5-year survival rate, result in a bleak prognosis. Exosomes, small extracellular vesicles released by various cells, contain diverse non-coding RNA molecules, including circular RNAs (circRNAs), which play a significant role in intercellular communication and can impact HCC progression. Studies have revealed the potential clinical applications of exosomal circRNAs as biomarkers and therapeutic targets for HCC. These circRNAs can be transferred via exosomes to nearby non-cancerous cells, thereby regulating HCC progression and influencing malignant phenotypes, such as cell proliferation, invasion, metastasis, and drug resistance. This review provides a comprehensive overview of the identified exosomal circRNAs, highlighting their potential as non-invasive biomarkers for HCC, and suggesting new perspectives for HCC diagnosis and treatment. The circRNA from exosomal organelles promotes metastasis and immune scape because of their unique chirality which is different from the Biomolecular Homochirality.

A diverse range of gastrointestinal tract disorders are called gastrointestinal (GI) malignancies. The transformation of normal cells into precursor cells, precursor cells into premalignant cells, and premalignant cells into cancerous cells is facilitated by the interaction of many modifiable and non-modifiable risk factors. Developing relevant therapy alternatives based on a better knowledge of the illness's aetiology is essential to enhance patient outcomes. The exosome is crucial in regulating intercellular interaction because it may send molecular signals to nearby or distant cells. Exosomes produced from cancer can introduce a variety of chemicals and vast concentrations of microRNA (miRNA) into the tumour microenvironment. These miRNAs significantly impact immunological evasion, metastasis, apoptosis resistance, and cell growth. Exosomal miRNAs, or exosomal miRNAs, are essential for controlling cancer resistance to apoptosis, according to mounting data. Exosomal miRNAs function as an interaction hub between cancerous cells and the milieu around them, regulating gene expression and various signalling pathways. Our research examines the regulatory function of exosomal miRNAs in mediating interactions between cancer cells and the stromal and immunological cells that make up the surrounding milieu.

Dysfunction of retinal vascularization plays pathogenic roles in retinopathy of prematurity (ROP). Hypoxia-inducible factor 1 alpha (HIF1A) is activated by hypoxia and contributes to ROP progression. Herein, we clarified the mechanism underlying HIF1A activation in human retinal vascular endothelial cells (HRECs) under hypoxia.

Protein expression was assayed by immunoblot analysis. Cell migration, microtubule formation, invasion, proliferation, and viability were detected by wound-healing, tube formation, transwell, EdU, and CCK-8 assays, respectively. Bioinformatics was used to predict the deubiquitinase-HIF1A interactions and RNA binding proteins (RBPs) bound to USP33. The impact of USP33 on HIF1A deubiquitination was validated by immunoprecipitation (IP) assay. RNA stability analysis was performed with actinomycin D (Act D) treatment. The ELAVL1/USP33 interaction was assessed by RNA immunoprecipitation experiment.

In hypoxia-exposed HRECs, HIF1A and USP33 protein levels were upregulated. Deficiency of HIF1A or USP33 suppressed cell migration, proliferation and microtubule formation of hypoxia-exposed HRECs. Mechanistically, USP33 deficiency led to an elevation in HIF1A ubiquitination and degradation. USP33 deficiency reduced HIF1A protein levels to suppress the proliferation and microtubule formation of hypoxia-induced HRECs. Moreover, the RBP ELAVL1 stabilized USP33 mRNA to increase USP33 protein levels. ELAVL1 decrease repressed the proliferation and microtubule formation of hypoxia-induced HRECs by reducing USP33.

Our study identifies a novel ELAVL1/USP33/HIF1A regulatory cascade with the ability to affect hypoxia-induced pathological proliferation, angiogenesis, and migration in HRECs.

Circular RNAs (circRNAs) represent a distinct class of covalently closed RNA species lacking conventional 5' to 3' polarity. Derived predominantly from pre-mRNA transcripts of protein-coding genes, circRNAs arise through back-splicing events of exon-exon or exon-intron junctions. They exhibit tissue- and cell-specific expression patterns and play crucial roles in regulating fundamental cellular processes such as cell cycle dynamics, proliferation, apoptosis, and differentiation. CircRNAs modulate gene expression through a plethora of mechanisms at epigenetic, transcriptional, and post-transcriptional levels, and some can even undergo translation into functional proteins. Recently, aberrant expression of circRNAs has emerged as a significant molecular aberration within the intricate regulatory networks governing hallmarks of cancer. The tumor-specific expression patterns and remarkable stability of circRNAs have profound implications for cancer diagnosis, prognosis, and therapy. This review comprehensively explores the multifaceted roles of circRNAs across cancer hallmarks in various tumor types, underscoring their growing significance in cancer diagnosis and therapeutic interventions. It also details strategies for leveraging circRNA-based therapies and discusses the challenges in using circRNAs for cancer management, emphasizing the need for further research to overcome these obstacles.

Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back-splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs' functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in-depth examination of circRNAs, focusing first on their involvement in non-neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs' roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions.

Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner.

Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer.

In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery.

The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

Aberrant expression of circular RNAs (circRNAs) is frequently linked to colorectal cancer (CRC). Here, we identified circZFR as a promising biomarker for CRC diagnosis and prognosis. CircZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence, advanced-stages, and metastasis. In both in vitro and in vivo settings, circZFR promoted the growth and spread while suppressing apoptosis of CRC. Exosomes with circZFR overexpression promoted the proliferation and migration of cocultured CRC cells. Mechanistically, epithelial splicing regulatory protein 1 (ESRP1) in CRC cells may enhance the production of circZFR. BCL2-associated transcription factor 1 (BCLAF1) bound to circZFR, which prevented its ubiquitinated degradation. Additionally, circZFR sponged miR-3127-5p to boost rhotekin 2 (RTKN2) expression. Our TCP1-CD-QDs nanocarrier was able to carry and deliver circZFR siRNA (si-circZFR) to the vasculature of CRC tissues and cells, which inhibited the growth of tumors in patient-derived xenograft (PDX) models. Taken together, our results show that circZFR is an oncogenic circRNA, which promotes the development and spread of CRC in a BCLAF1 and miR-3127-5p-dependent manner. CircZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

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.

Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack of reliable early detection techniques, a majority of patients have a poor prognosis. Therefore, identifying new tumor biomarkers and therapeutic targets is essential. This review aims to provide fresh insights into enhancing the prognosis of patients with GC by summarizing the processes through which microRNAs (miRNAs) regulate the tumor microenvironment (TME) and highlighting their critical role in the TME.

A comprehensive literature review was conducted by focusing on the interactions among tumor cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, and immune cells within the GC TME. The role of noncoding RNAs, known as miRNAs, in modulating the TME through various signaling pathways, cytokines, growth factors, and exosomes was specifically examined. Tumor formation, metastasis, and therapy in GC are significantly influenced by interactions within the TME. miRNAs regulate tumor progression by modulating these interactions through multiple signaling pathways, cytokines, growth factors, and exosomes. Dysregulation of miRNAs affects critical cellular processes such as cell proliferation, differentiation, angiogenesis, metastasis, and treatment resistance, contributing to the pathogenesis of GC.

miRNAs play a crucial role in the regulation of the GC TME, influencing tumor progression and patient prognosis. By understanding the mechanisms through which miRNAs control the TME, potential biomarkers and therapeutic targets can be identified to improve the prognosis of patients with GC.

A cutting-edge approach in cell-based immunotherapy for combating resistant cancer involves genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes. In recent years, these therapies have demonstrated effectiveness, leading to their commercialization and clinical application against certain types of cancer. However, CAR-T therapy faces limitations, such as the immunosuppressive tumour microenvironment (TME) that can render CAR-T cells ineffective, and the adverse side effects of the therapy, including cytokine release syndrome (CRS). Extracellular vesicles (EVs) are a diverse group of membrane-bound particles released into the extracellular environment by virtually all cell types. They are essential for intercellular communication, transferring cargoes such as proteins, lipids, various types of RNAs, and DNA fragments to target cells, traversing biological barriers both locally and systemically. EVs play roles in numerous physiological processes, with those from both immune and non-immune cells capable of modulating the immune system through activation or suppression. Leveraging this capability of EVs to enhance CAR-T cell therapy could represent a significant advancement in overcoming its current limitations. This review examines the current landscape of CAR-T cell immunotherapy and explores the potential role of EVs in augmenting its therapeutic efficacy.