1
|
Ying Q, Lv D, Chen Y, Mu Q. Distinguishing acute leukemia subtypes: The role of hsa_circ_0012152 and hsa_circ_0020093 in peripheral blood. Oncol Lett 2025; 30:330. [PMID: 40385694 PMCID: PMC12082030 DOI: 10.3892/ol.2025.15076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 03/06/2025] [Indexed: 05/20/2025] Open
Abstract
Acute leukemia (AL), a rapidly progressing hematological malignancy originating from the bone marrow, is primarily subclassified into acute myelocytic leukemia (AML) and acute lymphoblastic leukemia (ALL). Obtaining bone marrow samples can be challenging due to a number of reasons, including dilution or inaccessibility. Therefore, the present study focused on identifying novel diagnostic biomarkers in the peripheral blood for AL subgroups. Circular RNAs (circRNAs) are non-coding RNA molecules associated with various diseases. In the present study, to validate the distinct circRNA expression patterns distinguishing AML from ALL in peripheral blood, reverse transcription-quantitative polymerase chain reaction was employed. The diagnostic accuracy of hsa_circ_0020093 and hsa_circ_0012152 was then assessed using receiver operating characteristic curve analysis, and hsa_circ_0020093 was selected for further exploration using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The findings revealed that the expression patterns of hsa_circ_0020093 and hsa_circ_0012152 clearly differentiated ALL from AML in peripheral blood. The potential target genes of hsa_circ_0020093 identified were associated with critical biological processes such as protein serine kinase activity and cadherin binding. Furthermore, these genes are involved in signaling pathways including MAPK and mTOR. We propose that hsa_circ_0020093 plays a crucial role in initiating and promoting ALL by modulating downstream target genes through either hsa-microRNA (miR)-153-3p or hsa-miR-194-5p. The results of the present study demonstrate that hsa_circ_0020093 and hsa_circ_0012152 hold significant promise as diagnostic biomarkers for subclassifying AL into ALL or AML in peripheral blood. This discovery lays the foundation for future research endeavors aimed at elucidating the role of circRNAs in the pathogenesis and treatment of AL.
Collapse
Affiliation(s)
- Qiming Ying
- Department of Blood Transfusion, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China
| | - Dingfeng Lv
- Department of Blood Transfusion, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China
| | - Ying Chen
- Department of Hematology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China
| | - Qitian Mu
- Department of Hematology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China
| |
Collapse
|
2
|
Xu Q, Peng A, Zhao L, Wang L. Down-regulated circ_0001853 inhibits lipopolysaccharide-induced endometritis progression via sponging miR-34c-5p. Mol Cell Probes 2025; 81:102023. [PMID: 40058671 DOI: 10.1016/j.mcp.2025.102023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 03/01/2025] [Accepted: 03/06/2025] [Indexed: 03/18/2025]
Abstract
BACKGROUND To investigate the diagnostic value and mechanism of action of circular RNA (circ_) circ_0001853 and microRNA (miR) miR-34c-5p in patients with endometritis. METHODS 189 patients with endometritis and 176 healthy individuals were included in this study. Venous blood serum was collected from the study subjects and stored temporarily at -80 °C. Real-time quantitative chain polymerase reaction (RT-qPCR) was used to detect circ_0001853 and miR-34c-5p expression, and receiver operating characteristic (ROC) curves assessed the diagnostic value of both in predicting endometritis. Cell counting kit (CCK8) observed cell proliferation, flow cytometry recorded apoptosis, enzyme linked immunosorbent assay (ELISA) monitored inflammatory factor expression, and dual luciferase reporter assay and RNA immunoprecipitation (RIP) verified the relationship between circ_0001853 and miR-34c-5p targeting interactions. RESULTS High levels of circ_0001853 and low levels of miR-34c-5p were present in endometritis patients, and they were negatively correlated. Both circ_0001853 and miR-34c-5p alone or in combination had diagnostic value in predicting the progression of endometritis. Transfection of si-circ_0001853 promoted cell proliferation and reduced apoptosis and cellular inflammation levels induced by lipopolysaccharide (LPS) stimulation. There was a direct reciprocal targeting relationship between miR-34c-5p and circ_0001853, and the use of miR-34c-5p inhibitor resisted silencing circ_0001853 promoted cell proliferation and increased the number of apoptotic cells and cellular inflammation levels. CONCLUSIONS circ_0001853 is involved in endometritis progression through miR-34c-5p, i.e., low circ_0001853 promotes miR-34c-5p-induced proliferation of epithelial cells, reduces apoptosis, and suppresses inflammation levels, preventing disease progression.
Collapse
Affiliation(s)
- Qian Xu
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China
| | - Ailing Peng
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China
| | - Liyun Zhao
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China
| | - Li Wang
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China.
| |
Collapse
|
3
|
Sun G, Zheng M, Fan Y, Pan X. MVGNCDA: Identifying Potential circRNA-Disease Associations Based on Multi-view Graph Convolutional Networks and Network Embeddings. Interdiscip Sci 2025; 17:449-462. [PMID: 39962021 DOI: 10.1007/s12539-025-00690-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 01/07/2025] [Accepted: 01/09/2025] [Indexed: 05/28/2025]
Abstract
Increasing evidences have indicated that circular RNAs play a crucial role in the onset and progression of various diseases. However, exploring potential disease-associated circRNAs using conventional experimental techniques remains both time-intensive and costly. Recently, various computational approaches have been developed to detect the circRNA-disease associations. Nevertheless, due to the sparsity of the data and the inefficient utilization of similarity representation, it is still a challenge to effectively detect unknown circRNA-disease associations using multisource data. In this work, we propose an innovative computational framework, MVGNCDA, which merges a multi-view graph convolutional network (GCN) and biased random walk-based network embeddings to evaluate potential circRNA-disease associations from multisource data. First, we calculate disease semantic similarity, circRNA functional similarity, and their Gaussian interaction profile (GIP) kernel and cosine similarity. MVGNCDA utilizes multi-view GCNs to extract local node embeddings of diseases and circRNAs in the context of multisource information. Then, we construct a heterogeneous network utilizing integrated similarity and verified circRNA-disease associations, which is subsequently used to learn global node embeddings. Furthermore, the final fused local and global node embeddings are decoded to evaluate the circRNA-disease associations using a bilinear decoder. The fivefold cross-validation results demonstrate that MVGNCDA outperforms existing methods across five public datasets. Moreover, case study also confirms that MVGNCDA is capable of efficiently identifying unknown circRNA-disease associations.
Collapse
Affiliation(s)
- Guicong Sun
- School of Computer Science and Information Security, Guilin University of Electronic Technology, Guilin, 541004, China
| | - Mengxin Zheng
- School of Computer Science and Information Security, Guilin University of Electronic Technology, Guilin, 541004, China
| | - Yongxian Fan
- School of Computer Science and Information Security, Guilin University of Electronic Technology, Guilin, 541004, China.
| | - Xiaoyong Pan
- Department of Automation, Key Laboratory of System Control and Information Processing, Ministry of Education of China, Institute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, Shanghai, 200240, China
| |
Collapse
|
4
|
Xu Q, Xu Y, Yang T, Tang Y, Yang Q. The Role of Hsa_circ_0087862/miR-149-5p/TRAF6 Regulatory Axis in Colorectal Cancer Progression. Appl Biochem Biotechnol 2025:10.1007/s12010-025-05283-4. [PMID: 40366539 DOI: 10.1007/s12010-025-05283-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/02/2025] [Indexed: 05/15/2025]
Abstract
Circular RNAs (circRNAs) have been reported to be associated with the progression of various tumors including colorectal cancer (CRC). However, the role and underlying mechanism of hsa_circ_0087862 in CRC remains unclear. Hsa_circ_0087862 expression in CRC tissues was analyzed using two GEO datasets (GSE138589 and GSE126094). Expression of hsa_circ_0087862, miR-149-5p and tumor necrosis factor receptor-associated factor 6 (TRAF6) in CRC cells was detected. The subcellular distribution of hsa_circ_0087862 was analyzed using a Cytoplasmic & Nuclear RNA Purification Kit. The function of hsa_circ_0087862 in CRC cells was detected using CCK-8, Transwell invasion assay, flow cytometry analysis, and Caspase-3 activity assay. The relationships between hsa_circ_0087862, miR-149-5p and TRAF6 were detected using luciferase reporter assay, RIP, or biotinylated RNA pull-down assay. Hsa_circ_0087862 was upregulated in CRC tissues and cells. Hsa_circ_0087862 is resistant to RNase R digestion and predominantly localized in the cytoplasm. Interference with hsa_circ_0087862 inhibited the malignant phenotypes of CRC cells by reducing cell proliferation and invasive abilities and triggering apoptosis. Hsa_circ_0087862 silencing inhibited TRAF6 expression by sponging miR-149-5p in CRC cells. Inhibition of miR-149-5p attenuated the effects of hsa_circ_0087862 on the malignant phenotypes of CRC cells. TRAF6 overexpression abolished the effects of miR-149-5p on cell growth, invasion and apoptosis in CRC cells. In conclusion, hsa_circ_0087862 silencing inhibited the malignant behaviors of CRC cells through inhibiting TRAF6 expression by sponging miR-149-5p.
Collapse
Affiliation(s)
- Qiu Xu
- Department of Thyroid and Breast Surgery, Nanyang First People's Hospital, Nanyang, 473004, China
- Nanyang Key Laboratory of Thyroid Tumor Prevention and Treatment, Nanyang First People's Hospital, Nanyang, 473004, China
| | - Yi Xu
- Department of General Surgery, Nanyang First People's Hospital, Nanyang, 473004, China
| | - Tianyao Yang
- Department of General Surgery, People's Hospital of Tiantai County, Taizhou, 317299, China
| | - Yan Tang
- Department of General Surgery, Nanyang First People's Hospital, Nanyang, 473004, China
| | - Qiong Yang
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Shangtang Road 158, Hangzhou, 310014, China.
| |
Collapse
|
5
|
Song B, Fu J, Qian J, He T, Cheng J, Chiampanichayakul S, Anuchapreeda S, Fu J. Development of Mathematical Models Using circRNA Combinations ( circTulp4, circSlc8a1, and circStrn3) in Mouse Brain Tissue for Postmortem Interval Estimation. Int J Mol Sci 2025; 26:4495. [PMID: 40429639 PMCID: PMC12111416 DOI: 10.3390/ijms26104495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/28/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
The postmortem interval (PMI) is defined as the time interval between physiological death and the examination of the corpse, playing a critical role in forensic investigations. Traditional PMI estimation methods are often influenced by subjective and environmental factors. Circular RNAs (circRNAs), known for their stability, abundance, and conservation in brain tissue, show promise as biomarkers for PMI estimation. However, research on circRNAs in this context remains limited. This study aimed to develop PMI estimation models using circRNAs across multiple temperatures. By employing semi-quantitative reverse transcription-PCR, circTulp4, circSlc8a1, and circStrn3 were identified as reliable biomarkers for mouse brain tissue. Mathematical models were constructed using the reference genes 28S rRNA, mt-co1, and circCDR1as. At 4 °C, most equations had p-values below 0.05, with the equation using circSlc8a1 as a marker exhibiting the highest goodness of fit. Validation results indicated that the equation using circTulp4 as the reference gene had the highest accuracy. When applying the combined aforementioned three circRNAs, the equation using circCDR1as as the reference gene showed better accuracy. At 25 °C, all equations had R2 values greater than 0.86, but most cubic equations had p-values above 0.05. Validation results demonstrated that the circTulp4/mt-co1 equation had the highest accuracy. When applying combined circRNAs, the R2 values improved, and long-term PMI estimation was more accurate than short-term PMI estimation. At 35 °C, the linear equations had significantly poorer goodness of fit compared to nonlinear equations, and nonlinear equations exhibited better accuracy than linear equations. When applying the combined aforementioned three circRNAs, the accuracy of the three reference genes was similar, and the accuracy of long-term PMI estimation was consistently higher than that of short-term estimation. For the three-dimensional models, all R2 values exceeded 0.75 with p-values significantly below 0.0001. Validation results demonstrated higher accuracy at 25 °C and 35 °C, with superior performance for long-term PMI estimation. In summary, this study constructed PMI estimation models under multiple temperature conditions based on highly expressed circRNAs in mouse brain tissue, highlighting circTulp4, circSlc8a1, and circStrn3 as novel biomarkers. These findings offer a complementary tool for PMI estimation, particularly for long-term PMI estimation.
Collapse
Affiliation(s)
- Binghui Song
- Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (B.S.); (S.C.)
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China; (J.F.); (J.Q.); (T.H.); (J.C.)
- Laboratory of Precision Medicine and DNA Forensic Medicine, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
| | - Jiewen Fu
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China; (J.F.); (J.Q.); (T.H.); (J.C.)
- Laboratory of Precision Medicine and DNA Forensic Medicine, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Laboratory of Forensic DNA, The Judicial Authentication Center, Southwest Medical University, Luzhou 646000, China
| | - Jie Qian
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China; (J.F.); (J.Q.); (T.H.); (J.C.)
- Laboratory of Precision Medicine and DNA Forensic Medicine, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Laboratory of Forensic DNA, The Judicial Authentication Center, Southwest Medical University, Luzhou 646000, China
| | - Ting He
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China; (J.F.); (J.Q.); (T.H.); (J.C.)
- Laboratory of Precision Medicine and DNA Forensic Medicine, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Laboratory of Forensic DNA, The Judicial Authentication Center, Southwest Medical University, Luzhou 646000, China
| | - Jingliang Cheng
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China; (J.F.); (J.Q.); (T.H.); (J.C.)
- Laboratory of Precision Medicine and DNA Forensic Medicine, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Laboratory of Forensic DNA, The Judicial Authentication Center, Southwest Medical University, Luzhou 646000, China
| | - Sawitree Chiampanichayakul
- Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (B.S.); (S.C.)
- Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Songyot Anuchapreeda
- Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (B.S.); (S.C.)
- Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Junjiang Fu
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China; (J.F.); (J.Q.); (T.H.); (J.C.)
- Laboratory of Precision Medicine and DNA Forensic Medicine, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, China
- Laboratory of Forensic DNA, The Judicial Authentication Center, Southwest Medical University, Luzhou 646000, China
| |
Collapse
|
6
|
Zhu X, Gu G, Shen Y, Abdurazik MH, Liu C, Sun G. Nsclc-derived exosomal hsa_circ_0003026 promotes tumor growth through macrophage M2 polarization via hsa-miR-1183/XRN2 axis. Gene 2025; 962:149557. [PMID: 40345505 DOI: 10.1016/j.gene.2025.149557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 04/12/2025] [Accepted: 05/06/2025] [Indexed: 05/11/2025]
Abstract
OBJECTIVE Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. This study aimed to investigate the role of exosomal hsa_circ_0003026 in NSCLC progression and its underlying mechanism, particularly focusing on its effect on tumor-associated macrophage polarization. METHODS Exosomes were isolated from serum samples of NSCLC patients and cell lines, and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), and western blot. The expression of hsa_circ_0003026 was analyzed by qRT-PCR. Macrophage polarization was assessed by examining M1/M2 markers through qRT-PCR, Western blot, and ELISA. The interaction between hsa_circ_0003026 and hsa-miR-1183, as well as between hsa-miR-1183 and XRN2, was verified using dual-luciferase reporter, RIP, and RNA pull-down assays. The effects on tumor growth were evaluated using EdU proliferation assay, CCK-8 assay, and xenograft mouse models. RESULTS Exosomal hsa_circ_0003026 levels were significantly elevated in both NSCLC patients' serum and cell lines compared to controls. A549 cell-derived exosomes induced macrophage M2 polarization, which was dependent on hsa_circ_0003026. Mechanistically, hsa_circ_0003026 functioned as a molecular sponge for hsa-miR- 1183, thereby regulating XRN2 expression. Knockdown of hsa_circ_0003026 in exosomes significantly impaired their ability to induce M2 polarization, while inhibition of hsa-miR-1183 or overexpression of XRN2 rescued this effect. Furthermore, coculture with exosome-treated macrophages promoted NSCLC growth both in vitro and in vivo, which was attenuated when hsa_circ_0003026 was silenced. CONCLUSION Our findings reveal a novel mechanism whereby NSCLC-derived exosomal hsa_circ_0003026 promotes tumor progression by inducing M2 macrophage polarization through the hsa-miR-1183/XRN2 axis, suggesting potential therapeutic strategies for NSCLC treatment.
Collapse
Affiliation(s)
- Xiaodan Zhu
- Department of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, PR China
| | - Guomin Gu
- Department of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, PR China
| | - Yanli Shen
- Department of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, PR China
| | - Mi-Hray Abdurazik
- Department of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, PR China
| | - Chunling Liu
- Department of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, PR China.
| | - Gang Sun
- Department of Breast and Thyroid Surgery, People's hospital of Xinjiang Uygur Autonomous Region, PR China; Key Laboratory of Oncology of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, PR China.
| |
Collapse
|
7
|
Mahajan M, Hemberg M. Detecting known neoepitopes, gene fusions, transposable elements, and circular RNAs in cell-free RNA. Bioinformatics 2025; 41:btaf138. [PMID: 40315130 PMCID: PMC12057812 DOI: 10.1093/bioinformatics/btaf138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 01/26/2025] [Accepted: 04/30/2025] [Indexed: 05/04/2025] Open
Abstract
MOTIVATION Cancer is the second leading cause of death worldwide, and although there have been advances in treatments, including immunotherapies, these often require biopsies which can be costly and invasive to obtain. Due to lack of pre-emptive cancer detection methods, many cases of cancer are detected at a late stage when the definitive symptoms appear. Plasma samples are relatively easy to obtain, and they can be used to monitor the molecular signatures of ongoing processes in the body. Profiling cell-free DNA is a popular method for monitoring cancer, but only a few studies have explored the use of cell-free RNA (cfRNA), which shows the recent footprint of systemic transcription. RESULTS Here, we developed FastNeo, a computational method for detecting known neoepitopes in human cfRNA. We show that neoepitopes and other biomarkers detected in cfRNA can discern Hepatocellular carcinoma patients from the healthy patients with a sensitivity of 0.84 and a specificity of 0.79. For colorectal cancer we achieve a sensitivity of 0.87 and a specificity of 0.8. An important advantage of our cfRNA based approach is that it also reports putative neoepitopes which are important for therapeutic purposes. AVAILABILITY AND IMPLEMENTATION The FastNeo package is available at https://github.com/yashumayank/FastNeo and https://zenodo.org/records/11521368. The benchmark pipelines to detect Immune Epitope database and Tumor-Specific Neoantigen database neoepitopes using HaplotypeCaller, bcftools, and Lofreq, and to run FastNeo with STAR instead of Bowtie2 are also available in the above github repository.
Collapse
Affiliation(s)
- Mayank Mahajan
- Gene Lay Institute of Immunology and Inflammation, Brigham and Women’s Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, United States
| | - Martin Hemberg
- Gene Lay Institute of Immunology and Inflammation, Brigham and Women’s Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, United States
| |
Collapse
|
8
|
Owida HA, Saleh RO, Mohammad SI, Vasudevan A, Roopashree R, Kashyap A, Nanda A, Ray S, Hussein A, Yasin HA. Deciphering the role of circular RNAs in cancer progression under hypoxic conditions. Med Oncol 2025; 42:191. [PMID: 40314834 DOI: 10.1007/s12032-025-02727-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Accepted: 04/14/2025] [Indexed: 05/03/2025]
Abstract
Hypoxia, characterized by reduced oxygen levels, plays a pivotal role in cancer progression, profoundly influencing tumor behavior and therapeutic responses. A hallmark of solid tumors, hypoxia drives significant metabolic adaptations in cancer cells, primarily mediated by hypoxia-inducible factor-1α (HIF-1α), a key transcription factor activated in low-oxygen conditions. This hypoxic environment promotes epithelial-mesenchymal transition (EMT), enhancing cancer cell migration, metastasis, and the development of cancer stem cell-like properties, which contribute to therapy resistance. Moreover, hypoxia modulates the expression of circular RNAs (circRNAs), leading to their accumulation in the tumor microenvironment. These hypoxia-responsive circRNAs regulate gene expression and cellular processes critical for cancer progression, making them promising candidates for diagnostic and prognostic biomarkers in various cancers. This review delves into the intricate interplay between hypoxic circRNAs, microRNAs, and RNA-binding proteins, emphasizing their role as molecular sponges that modulate gene expression and signaling pathways involved in cell proliferation, apoptosis, and metastasis. It also explores the relationship between circRNAs and the tumor microenvironment, particularly how hypoxia influences their expression and functional dynamics. Additionally, the review highlights the potential of circRNAs as diagnostic and prognostic tools, as well as their therapeutic applications in innovative cancer treatments. By consolidating current knowledge, this review underscores the critical role of circRNAs in cancer biology and paves the way for future research aimed at harnessing their unique properties for clinical advancements. Specifically, this review examines the biogenesis, expression patterns, and mechanistic actions of hypoxic circRNAs, focusing on their ability to act as molecular sponges for microRNAs and their interactions with RNA-binding proteins. These interactions impact key signaling pathways related to tumor growth, metastasis, and drug resistance, offering new insights into the complex regulatory networks governed by circRNAs under hypoxic stress.
Collapse
Affiliation(s)
- Hamza Abu Owida
- Department of Medical Engineering, Faculty of Engineering, Al-Ahliyya Amman University, Amman, Jordan
| | - Raed Obaid Saleh
- Department of Medical Laboratories Techniques, College of Health and Medical Techniques, University of Al Maarif, Al Anbar, 31001, Iraq.
| | - Suleiman Ibrahim Mohammad
- Research Follower, INTI International University, 71800, Negeri Sembilan, Malaysia.
- Electronic Marketing and Social Media, Economic and Administrative Sciences, Zarqa University, Zarqa, Jordan.
| | - Asokan Vasudevan
- Faculty of Business and Communications, INTI International University, 71800, Negeri Sembilan, Malaysia
| | - R Roopashree
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Aditya Kashyap
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
| | - Anima Nanda
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Subhashree Ray
- Department of Biochemistry, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, 751003, India
| | - Ahmed Hussein
- Medical Laboratory Technique College, The Islamic University, Najaf, Iraq
| | - Hatif Abdulrazaq Yasin
- Department of Medical Laboratories Technology, Al-Nisour University College, Nisour Seq. Karkh, Baghdad, Iraq
| |
Collapse
|
9
|
Li H, Liu H, Zhou Y, Cheng L, Wang B, Ma J. The multifaceted roles of extracellular vesicles in osteonecrosis of the femoral head. J Orthop Translat 2025; 52:70-84. [PMID: 40256260 PMCID: PMC12008682 DOI: 10.1016/j.jot.2025.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/22/2025] Open
Abstract
Osteonecrosis of the femoral head (ONFH) is a severe disease characterized by bone tissue necrosis due to vascular impairment, often leading to joint collapse and requiring surgical intervention. Extracellular vesicles (EVs) serve as crucial mediators of intercellular communication, influencing osteogenesis, angiogenesis, and immune regulation. This review summarizes the dual role of EVs in both the pathogenesis of ONFH and post-necrosis bone repair, highlighting the impact of various EV-mediated signaling pathways on bone regeneration and the potential crosstalk among these pathways. Additionally, EVs hold promise as diagnostic biomarkers or contrast agents to complement conventional imaging techniques for ONFH detection. By elucidating the role of EVs in osteonecrosis and addressing the current challenges, we aspire to establish a foundation for the timely identification and treatment of ONFH. The translational potential of this article: This review comprehensively discusses the role of EVs in ONFH, providing innovative and promising insights for its diagnosis and treatment, which also establishes a theoretical foundation for the future clinical application of EVs in ONFH.
Collapse
Affiliation(s)
- Hongxu Li
- Department of Orthopaedic Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
| | - Haoyang Liu
- Department of Orthopaedic Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
| | - Yu Zhou
- Department of Orthopaedic Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
| | - Liming Cheng
- Department of Orthopaedic Surgery, Center for Osteonecrosis and Joint Preserving & Reconstruction, China-Japan Friendship Hospital, Beijing, 100029, China
| | - Bailiang Wang
- Department of Orthopaedic Surgery, Center for Osteonecrosis and Joint Preserving & Reconstruction, China-Japan Friendship Hospital, Beijing, 100029, China
| | - Jinhui Ma
- Department of Orthopaedic Surgery, Center for Osteonecrosis and Joint Preserving & Reconstruction, China-Japan Friendship Hospital, Beijing, 100029, China
| |
Collapse
|
10
|
Wang W, Li X, Wang H, Huang C, Zhu L, Wang H, Zhang W. CircDIAPH1 Promotes Liver Metastasis and Development of Colorectal Cancer by Initiation of CEACAM6 Expression. Mol Carcinog 2025; 64:897-910. [PMID: 39987565 DOI: 10.1002/mc.23896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/25/2025] [Accepted: 02/10/2025] [Indexed: 02/25/2025]
Abstract
Liver metastasis is a critical factor influencing the 5-year survival rate in colorectal cancer (CRC). However, the biological function of most circRNAs in liver metastasis of CRC is still unknown. In this study, we identified differentially expressed circRNAs associated with liver metastasis (LM-DE-circRNAs). A total of 247 LM-DE-circRNAs were identified, and crucial signaling pathways, including the regulation of actin cytoskeleton, were significantly enriched, featuring six LM-DE-circRNAs. Notably, circDIAPH1 (hsa_circ_0074323), with the highest AUC value, emerged as a potential biomarker for CRC liver metastasis (CRLM). Functional assays following circDIAPH1 knockdown demonstrated induced apoptosis, suppressed proliferation, reduced metastasis, and invasion in CRC cell lines in vitro. The circDIAPH1 knockdown attenuated tumor growth in a cell-derived xenograft model. Furthermore, circDIAPH1 knockdown lessened the liver metastasis. Transcriptome profiling revealed that CEACAM6 was the most downregulated gene while circDIAPH1 was knocked down, and possesses high expression value in CRC. Most importantly, we found that circDIAPH1 recruited transcription factor FOXA1 to bind in the promoter region of CEACAM6 and initiated CEACAM6 expression. Additionally, the study identified the transcription factor BRD4 as a regulator of circDIAPH1 expression in CRC. In conclusion, this study reveals that circDIAPH1 recruits FOXA1 to initiate CEACAM6 expression, promoting liver metastasis and development of CRC.
Collapse
Affiliation(s)
- Wei Wang
- Department of Colorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Xu Li
- Department of Colorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Hantao Wang
- Department of Colorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Cheng Huang
- Department of Colorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Laicheng Zhu
- Department of Colorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Hao Wang
- Department of Colorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Wei Zhang
- Department of Colorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| |
Collapse
|
11
|
Yin H, Shi J, Li S, You Q, Zhu H, Koo C, Liu B, Hou L, Wu C. Emerging roles of exosomal circRNAs in non-small cell lung cancer. J Transl Med 2025; 23:490. [PMID: 40307927 PMCID: PMC12042431 DOI: 10.1186/s12967-025-06463-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 04/06/2025] [Indexed: 05/02/2025] Open
Abstract
Despite the prevalence of non-small cell lung cancer (NSCLC) is high, the limited early detection and management of these tumors are restricted since there is an absence of reliable and precise diagnostic biomarkers and therapeutic targets. Exosomes transport functional molecules for facilitating intercellular communication, especially in the tumor microenvironment, indicating their potential as cancer biomarkers and therapeutic targets. Circular RNA (circRNA), a type of non-coding RNA possessing a covalently closed loop structure, substantial abundance, and tissue-specific expression patterns, is stably enriched in exosomes. In recent years, significant breakthroughs have been made in research on exosomal circRNA in NSCLC. This review briefly introduces the biogenesis, characterizations, and functions of circRNAs and exosomes, and systematically describes the biological functions and mechanisms of exosomal circRNAs in NSCLC. In addition, this study summarizes their role in the progression of NSCLC and discusses their clinical significance as biomarkers and therapeutic targets for NSCLC.
Collapse
Affiliation(s)
- Hongyuan Yin
- Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jiayi Shi
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Shaoling Li
- Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China
| | - Qianhui You
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Huici Zhu
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Chinying Koo
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Baonian Liu
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Likun Hou
- Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
| | - Chunyan Wu
- Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
| |
Collapse
|
12
|
Liu S, Wan X, Gou Y, Yang W, Xu W, Du Y, Peng X, Wang X, Zhang X. The emerging functions and clinical implications of circRNAs in acute myeloid leukaemia. Cancer Cell Int 2025; 25:167. [PMID: 40296024 PMCID: PMC12038945 DOI: 10.1186/s12935-025-03772-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 03/28/2025] [Indexed: 04/30/2025] Open
Abstract
Acute myeloid leukaemia (AML) is a prevalent haematologic malignancy characterized by significant heterogeneity. Despite the application of aggressive therapeutic approaches, AML remains associated with poor prognosis. Circular RNAs (circRNAs) constitute a unique class of single-stranded RNAs featuring covalently closed loop structures that are ubiquitous across species. These molecules perform crucial regulatory functions in the pathogenesis of various diseases through diverse mechanisms, including acting as miRNA sponges, interacting with DNA or proteins, and encoding functional proteins/polypeptides. Recently, numerous circRNAs have been confirmed to have aberrant expression patterns in AML patients. In particular, certain circRNAs are closely associated with specific clinicopathological characteristics and thus have great potential as diagnostic/prognostic biomarkers and therapeutic targets in AML. Herein, we systematically summarize the biogenesis, degradation, and functional mechanisms of circRNAs while highlighting their clinical relevance. We also outline a series of online databases and analytical tools available to facilitate circRNA research. Finally, we discuss the current challenges and future research priorities in this evolving field.
Collapse
Affiliation(s)
- Shuiqing Liu
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Xingyu Wan
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Yang Gou
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Wuchen Yang
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Wei Xu
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Yuxuan Du
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Xiangui Peng
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Xiaoqi Wang
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China
| | - Xi Zhang
- Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, China.
- Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, China.
- State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400037, China.
- Jinfeng Laboratory, Chongqing, 401329, China.
| |
Collapse
|
13
|
Zhao P, Yin C, Liu R, Shao S, Ke W, Song Z. Exosome-Delivered circFOXP1 Upregulates Autophagy and Promotes Hepatocellular Carcinoma Progression Through Its Encoded p196 Protein Targeting the KHDRBS3/ULK1 Axis. Int J Nanomedicine 2025; 20:5247-5265. [PMID: 40292405 PMCID: PMC12034270 DOI: 10.2147/ijn.s505157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 04/05/2025] [Indexed: 04/30/2025] Open
Abstract
Introduction Circular RNAs (circRNAs) are pivotal regulators in cancer, and circFOXP1 has been implicated in tumorigenesis. This study explores the exosome-mediated transfer of circFOXP1 and its functional protein product, p196, in hepatocellular carcinoma (HCC) progression. Methods HCC circRNA datasets were obtained from the Gene Expression Omnibus (GEO) databases, and circRNAs were validated via qRT-PCR and Sanger sequencing. Exosomes were isolated via ultracentrifugation and characterized by TEM/NTA. RIP, Co-IP, RNA pull-down and in vitro binding assays were employed to determine molecular interactions. Loss- and gain-of-function assays were employed to evaluate the effects of circFOXP1, KHDRBS3 and ULK1 on the proliferation, and invasion abilities of HCC cells both in vitro and in vivo. Results CircFOXP1, which encoded a 196-amino acid protein, p196, was highly expressed in HCC tissues and cells and secreted via exosomes. Overexpression of p196 enhanced HCC cell proliferation, invasion, and autophagy flux in vitro, while knockdown produced opposite effects. Mechanistically, p196 directly bound KHDRBS3 through its D2 domain, forming a complex that stabilized ULK1 mRNA, thereby increasing ULK1 protein levels, activating autophagy and accelerating tumor progression. Conclusion Our findings indicated that circFOXP1-encoded p196 plays a role as a tumor promoter, contributing to the malignant progression of HCC. Targeting the circFOXP1/p196-KHDRBS3-ULK1 axis presents a promising therapeutic strategy for HCC, with potential applications in biomarker development and combination therapies.
Collapse
Affiliation(s)
- Peng Zhao
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Chuanzheng Yin
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Ran Liu
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Shuyu Shao
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Wenbo Ke
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Zifang Song
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| |
Collapse
|
14
|
LIANG HAISU, YAN WEI, LIU ZHI, HE YUNBO, HU JIAO, SHU ZHIWEI, LI HUIHUANG, OTHMANE BELAYDI, REN WENBIAO, QUAN CHAO, QIU DONGXU, CHEN MINFENG, XIONG WEI, ZHANG BINGNAN, LIU PEIHUA. Immunomodulatory behavior of CircRNAs in tumor microenvironment. Oncol Res 2025; 33:1105-1119. [PMID: 40296917 PMCID: PMC12034001 DOI: 10.32604/or.2024.054623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 11/13/2024] [Indexed: 04/30/2025] Open
Abstract
Circular RNAs (circRNAs) are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms. Due to the lack of a free end that is typically susceptible to degradation by nucleases, circular RNAs exhibit resistance to ribonuclease R, making them highly stable in eukaryotic cells. The complex relationship between circRNA dysregulation and various pathophysiological conditions, especially cancer. Tumor microenvironment (TME) is a collective term for various components surrounding tumors and is an important factor affecting tumor development. Simultaneous infiltration of TME by different types of immune cells; These immune cells interact with the TME, collectively forming the so-called "tumor immune microenvironment". The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors, and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME. CircRNAs can directly or indirectly regulate immune cells, thereby modulating anti-tumor immunity. This review highlights how circRNAs, especially those encapsulated in extracellular vesicles like exosomes, influence the differentiation, chemotaxis, and anti-tumor immune functions of immune cells within the TME. Metabolic reprogramming plays an important role in this process. The process of circRNAs regulating tumor immunity is affected by multiple factors, such as hypoxia and viral infection. This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.
Collapse
Affiliation(s)
- HAISU LIANG
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - WEI YAN
- Department of Urology, Shimen Hospital of TCM, Changde, 415300, China
| | - ZHI LIU
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
- Department of Urology, The Second Affiliated Hospital, Guizhou Medical University, Kaili, 556000, China
| | - YUNBO HE
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410000, China
- NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - JIAO HU
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - ZHIWEI SHU
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - HUIHUANG LI
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - BELAYDI OTHMANE
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - WENBIAO REN
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
- George Whipple Lab for Cancer Research, University of Rochester Medical Institute, Rochester, NY 14627, USA
| | - CHAO QUAN
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - DONGXU QIU
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - MINFENG CHEN
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - WEI XIONG
- NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - BINGNAN ZHANG
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
| | - PEIHUA LIU
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410000, China
| |
Collapse
|
15
|
Zhang Y, Yue NN, Chen LY, Tian CM, Yao J, Wang LS, Liang YJ, Wei DR, Ma HL, Li DF. Exosomal biomarkers: A novel frontier in the diagnosis of gastrointestinal cancers. World J Gastrointest Oncol 2025; 17:103591. [PMID: 40235899 PMCID: PMC11995328 DOI: 10.4251/wjgo.v17.i4.103591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/24/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
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.
Collapse
Affiliation(s)
- Yuan Zhang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
- Department of Medical Administration, Huizhou Institute for Occupational Health, Huizhou 516000, Guangdong Province, China
| | - Ning-Ning Yue
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), Shenzhen 518000, Guangdong Province, China
| | - Li-Yu Chen
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People’s Hospital (Jinan University of Second Clinical Medical Sciences), Shenzhen 518000, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen 518000, Guangdong Province, China
| | - Dao-Ru Wei
- Department of Rehabilitation, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Hua-Lin Ma
- Department of Nephrology, The Second Clinical Medical College, Jinan University, Shenzhen 518020, Guangdong Province, China
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| |
Collapse
|
16
|
Ji J, Li M, Yan K, Ma J, Wei D, Zhang F, Qiao S, Huang P, Zhang W, Li L, Zheng W, Ren L. circSTIL mediates pirarubicin inhibiting the malignant phenotype of triple-negative breast cancer and acts as a biomarker in plasma exosomes. Mol Immunol 2025; 180:86-95. [PMID: 40022852 DOI: 10.1016/j.molimm.2025.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/04/2025]
Abstract
In clinical practice, pirarubicin (THP) is a widely used triple-negative breast cancer (TNBC) agent. It has been found that circular RNAs (circRNAs) are involved in cancer treatment and progression. However, the biological function of circRNAs in TNBC and the relationship between THP and circRNAs remain poorly studied. circSTIL (hsa_circ_0000069) was screened and validated by bioinformatics analysis, demonstrating that it was highly expressed in TNBC cell lines and plasma exosomes, and correlated with a poor prognosis of patients. The expression level of circSTIL in patients' plasma exosomes has potential diagnostic value in distinguishing TNBC from non-TNBC. In vitro studies confirmed that overexpression of circSTIL promotes the proliferation, migration, and invasion of MDA-MB-231 cells whereas silicification of circSTIL shows the reverse effect. Also, circSTIL mediates THP inhibiting the malignant phenotype of MDA-MB-231 cells. The above results suggested that circSTIL is a possible biomarker for the diagnosis, treatment, and prognosis of TNBC.
Collapse
Affiliation(s)
- Jiahua Ji
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Min Li
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Kaixu Yan
- Ultrasound Department, Obstetrics and Gynaecology Hospital of Jilin City, 53, Guanghua Road, Jilin City, Jilin 132000, China
| | - Jiulong Ma
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Dexian Wei
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Fan Zhang
- General Surgery Center, Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China
| | - Sennan Qiao
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Peng Huang
- School of Agroforestry and Medicine, The Open University of China, Beijing 100000, China
| | - Wenqing Zhang
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Lu Li
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Wentao Zheng
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China
| | - Liqun Ren
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China.
| |
Collapse
|
17
|
O'Leary E, Jiang Y, Kristensen LS, Hansen TB, Kjems J. The therapeutic potential of circular RNAs. Nat Rev Genet 2025; 26:230-244. [PMID: 39789148 DOI: 10.1038/s41576-024-00806-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2024] [Indexed: 01/12/2025]
Abstract
Over the past decade, research into circular RNA (circRNA) has increased rapidly, and over the past few years, circRNA has emerged as a promising therapeutic platform. The regulatory functions of circRNAs, including their roles in templating protein translation and regulating protein and RNA functions, as well as their unique characteristics, such as increased stability and a favourable immunological profile compared with mRNAs, make them attractive candidates for RNA-based therapies. Here, we describe the properties of circRNAs, their therapeutic potential and technologies for their synthesis. We also discuss the prospects and challenges to be overcome to unlock the full potential of circRNAs as drugs.
Collapse
Affiliation(s)
| | - Yanyi Jiang
- Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark
| | | | | | - Jørgen Kjems
- Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark.
- Department of Molecular Biology and Genetics (MBG), Aarhus University, Aarhus, Denmark.
| |
Collapse
|
18
|
Hatzimanolis O, Sykes AM, Cristino AS. Circular RNAs in neurological conditions - computational identification, functional validation, and potential clinical applications. Mol Psychiatry 2025; 30:1652-1675. [PMID: 39966624 PMCID: PMC11919710 DOI: 10.1038/s41380-025-02925-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 01/11/2025] [Accepted: 02/10/2025] [Indexed: 02/20/2025]
Abstract
Non-coding RNAs (ncRNAs) have gained significant attention in recent years due to advancements in biotechnology, particularly high-throughput total RNA sequencing. These developments have led to new understandings of non-coding biology, revealing that approximately 80% of non-coding regions in the genome possesses biochemical functionality. Among ncRNAs, circular RNAs (circRNAs), first identified in 1976, have emerged as a prominent research field. CircRNAs are abundant in most human cell types, evolutionary conserved, highly stable, and formed by back-splicing events which generate covalently closed ends. Notably, circRNAs exhibit high expression levels in neural tissue and perform diverse biochemical functions, including acting as molecular sponges for microRNAs, interacting with RNA-binding proteins to regulate their availability and activity, modulating transcription and splicing, and even translating into functional peptides in some cases. Recent advancements in computational and experimental methods have enhanced our ability to identify and validate circRNAs, providing valuable insights into their biological roles. This review focuses on recent developments in circRNA research as they related to neuropsychiatric and neurodegenerative conditions. We also explore their potential applications in clinical diagnostics, therapeutics, and future research directions. CircRNAs remain a relatively underexplored area of non-coding biology, particularly in the context of neurological disorders. However, emerging evidence supports their role as critical players in the etiology and molecular mechanisms of conditions such as schizophrenia, bipolar disorder, major depressive disorder, Alzheimer's disease, and Parkinson's disease. These findings suggest that circRNAs may provide a novel framework contributing to the molecular dysfunctions underpinning these complex neurological conditions.
Collapse
Affiliation(s)
- Oak Hatzimanolis
- Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD, Australia
| | - Alex M Sykes
- Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD, Australia
| | - Alexandre S Cristino
- Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD, Australia.
| |
Collapse
|
19
|
Karaca Dogan B, Salman Yilmaz S, Izgi GN, Ozen M. Circulating non-coding RNAs as a tool for liquid biopsy in solid tumors. Epigenomics 2025; 17:335-358. [PMID: 40040488 PMCID: PMC11970797 DOI: 10.1080/17501911.2025.2467021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 02/10/2025] [Indexed: 03/06/2025] Open
Abstract
Solid tumors are significant causes of global mortality and morbidity. Recent research has primarily concentrated on finding pathology-specific molecules that can be acquired non-invasively and that can change as the disease progresses or in response to treatment. The focus of research has moved to RNA molecules that are either freely circulating in body fluids or bundled in microvesicles and exosomes because of their great stability in challenging environments, ease of accessibility, and changes in level in response to therapy. In this context, there are many non-coding RNAs that can be used for this purpose in liquid biopsies. Out of these, microRNAs have been extensively studied. However, there has been an increase of interest in studying long non-coding RNAs, piwi interacting RNAs, circular RNAs, and other small non-coding RNAs. In this article, an overview of the most researched circulating non-coding RNAs in solid tumors will be reviewed, along with a discussion of the significance of these molecules for early diagnosis, prognosis, and therapeutic targets. The publications analyzed were extracted from the PubMed database between 2008 and June 2024.
Collapse
Affiliation(s)
- Beyza Karaca Dogan
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Seda Salman Yilmaz
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Medical Services and Techniques Medical Monitoring Techniques Pr. Vocational School of Health Services, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Gizem Nur Izgi
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Mustafa Ozen
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
| |
Collapse
|
20
|
Wang J, Zhang C, Zhang Y, Guo J, Xie C, Liu Y, Chen L, Ma L. Circular RNA in liver cancer research: biogenesis, functions, and roles. Front Oncol 2025; 15:1523061. [PMID: 40224186 PMCID: PMC11985449 DOI: 10.3389/fonc.2025.1523061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 03/11/2025] [Indexed: 04/15/2025] Open
Abstract
Liver cancer, characterized by its insidious nature, aggressive invasiveness, and propensity for metastasis, has witnessed a sustained increase in both incidence and mortality rates in recent years, underscoring the urgent need for innovative diagnostic and therapeutic approaches. Emerging research indicates that CircRNAs (circular RNAs) are abundantly and stably present within cells, with their expression levels closely associated with the progression of various malignancies, including hepatocellular carcinoma. In the context of liver cancer progression, circRNAs exhibit promising potential as highly sensitive diagnostic biomarkers, offering novel avenues for early detection, and also function as pivotal regulatory factors within the carcinogenic process. This study endeavors to elucidate the biogenesis, functional roles, and underlying mechanisms of circRNAs in hepatocellular carcinoma, thereby providing a fresh perspective on the pathogenesis of liver cancer and laying a robust foundation for the development of more precise and effective early diagnostic tools and therapeutic strategies.
Collapse
Affiliation(s)
- Jiayi Wang
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- School of Rehabilitation Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Congcong Zhang
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- School of Rehabilitation Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Yinghui Zhang
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Jiaojiao Guo
- School of Rehabilitation Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Chenyu Xie
- School of Rehabilitation Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Yulu Liu
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Lidian Chen
- School of Rehabilitation Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Liangliang Ma
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| |
Collapse
|
21
|
Mak CH, Wang GR, Li ZZ, Cao LM, Zhang CX, Zhu ZQ, Liu B, Bu LL. Hidden messages in fluids: A review of clinical and fundamental perspectives on post-lymph node dissection drains. Int J Cancer 2025; 156:1103-1113. [PMID: 39470623 DOI: 10.1002/ijc.35240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 10/30/2024]
Abstract
In recent years, there has been a growing interest in liquid biopsy due to its non-invasive diagnostic value. Postoperative drainage fluid (PDF) is the fluid exudate from the wound site following lymph node dissection. PDF is regarded as a medical waste with no specific clinical significance. Nevertheless, the liquid biopsy of PDF may enable the reuse of this fluid. PDF contains a variety of body fluids, including blood and lymph. PDF contains a variety of biological components, including cytokines, extracellular vesicles (EVs), proteins, nucleic acids, cells and bacteria. These components are indicative of the postoperative inflammatory response, the immune response and the therapeutic response. In this review, we examine the current state of research in the field of liquid biopsy in PDF, elucidating how the analysis of its components can assess the prognosis of patients after lymph node dissection, monitor real-time changes in patient status, and identify new biomarkers and potential therapeutic targets.
Collapse
Affiliation(s)
- Chon-Hou Mak
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Guang-Rui Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zi-Zhan Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lei-Ming Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Chen-Xi Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Zhao-Qi Zhu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Bing Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Oral & Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lin-Lin Bu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
- Department of Oral & Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
| |
Collapse
|
22
|
Chang H, Cai F, Li X, Li A, Zhang Y, Yang X, Liu X. Biomaterial-based circular RNA therapeutic strategy for repairing intervertebral disc degeneration. BIOMEDICAL TECHNOLOGY 2025; 9:100057. [DOI: 10.1016/j.bmt.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
23
|
Zhao M, Lin M, Zhang Z, Ye L. Research progress of circular RNA FOXO3 in diseases (review). Glob Med Genet 2025; 12:100003. [PMID: 39925449 PMCID: PMC11800306 DOI: 10.1016/j.gmg.2024.100003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/08/2024] [Accepted: 09/22/2024] [Indexed: 02/11/2025] Open
Abstract
Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs with a closed-loop structures, and they exert crucial regulatory functions in diverse biological processes and disease development through the modulation of linear RNA transcription, downstream gene expression, and protein translation, among others. Circular RNA FOXO3(circFOXO3, Hsa_circ_0006404) originates from exon 2 of the FOXO3 gene and exhibits widespread cytoplasmic expression in eukaryotic cells. It shows specific expression in different tissues or cells. Recent research has associated circFOXO3 with various diseases such as cancer, cardiovascular diseases, neurological disorders, senescence, and inflammation. However, a comprehensive review of the research progress of circFOXO3 in human diseases has not been conducted. In this paper, we provide a systematic review of the latest advances in circFOXO3 research in diseases, elucidate its biological functions and potential molecular mechanisms, and discuss the future directions and challenges in circRNAs research to provide valuable references and inspiration for research in this field.
Collapse
Affiliation(s)
- Min Zhao
- Good Clinical Practice(GCP) Institutional Office of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China
| | - Minting Lin
- Good Clinical Practice(GCP) Institutional Office of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China
| | - Zhibo Zhang
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), China
| | - Linhu Ye
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China
| |
Collapse
|
24
|
Liu W, Niu J, Huo Y, Zhang L, Han L, Zhang N, Yang M. Role of circular RNAs in cancer therapy resistance. Mol Cancer 2025; 24:55. [PMID: 39994791 PMCID: PMC11854110 DOI: 10.1186/s12943-025-02254-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 01/30/2025] [Indexed: 02/26/2025] Open
Abstract
Over the past decade, circular RNAs (circRNAs) have gained recognition as a novel class of genetic molecules, many of which are implicated in cancer pathogenesis via different mechanisms, including drug resistance, immune escape, and radio-resistance. ExosomalcircRNAs, in particular, facilitatecommunication between tumour cells and micro-environmental cells, including immune cells, fibroblasts, and other components. Notably, micro-environmental cells can reportedly influence tumour progression and treatment resistance by releasing exosomalcircRNAs. circRNAs often exhibit tissue- and cancer-specific expression patterns, and growing evidence highlights their potential clinical relevance and utility. These molecules show strong promise as potential biomarkers and therapeutic targets for cancer diagnosis and treatment. Therefore, this review aimed to briefly discuss the latest findings on the roles and resistance mechanisms of key circRNAs in the treatment of various malignancies, including lung, breast, liver, colorectal, and gastric cancers, as well as haematological malignancies and neuroblastoma.This review will contribute to the identification of new circRNA biomarkers for the early diagnosis as well as therapeutic targets for the treatment of cancer.
Collapse
Affiliation(s)
- Wenjuan Liu
- Shandong Provincial Key Laboratory of Precision Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China
| | - Jiling Niu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China
| | - Yanfei Huo
- Shandong Provincial Key Laboratory of Precision Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China
| | - Long Zhang
- Shandong Provincial Key Laboratory of Precision Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China
| | - Linyu Han
- Shandong Provincial Key Laboratory of Precision Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China
| | - Nasha Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China.
| | - Ming Yang
- Shandong Provincial Key Laboratory of Precision Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250117, China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China.
- School of Life Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, Shandong Province, China.
| |
Collapse
|
25
|
Ciferri MC, Tasso R. Extracellular vesicle-mediated chemoresistance in breast cancer: focus on miRNA cargo. EXTRACELLULAR VESICLES AND CIRCULATING NUCLEIC ACIDS 2025; 6:112-127. [PMID: 40206797 PMCID: PMC11977373 DOI: 10.20517/evcna.2024.90] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 01/14/2025] [Accepted: 02/05/2025] [Indexed: 04/11/2025]
Abstract
The role of extracellular vesicles (EVs) in mediating chemoresistance has gained significant attention due to their ability to transfer bioactive molecules between drug-resistant and drug-sensitive cells. In particular, they have been demonstrated to play an active part in breast cancer chemoresistance by the horizontal transfer of genetic and protein material. This review highlights the role of EVs, particularly their miRNA cargo, in driving drug resistance in breast cancer. EVs derived from chemoresistant cells carry miRNAs and lncRNAs, which are known to modulate gene networks involved in cell proliferation and survival. These cargo molecules suppress apoptosis by targeting pro-apoptotic genes like PTEN and BIM, promote epithelial-mesenchymal transition (EMT) through the regulation of pathways such as TGF-β and Wnt/b-catenin, and contribute to tumor growth and resistance by enhancing angiogenesis and modulating the tumor microenvironment. Beyond RNA-mediated effects, EVs also transfer functional proteins, including P-glycoprotein and Hsp70, which impact cellular metabolism and survival pathways. Our findings underscore the significance of EVs in breast cancer chemoresistance, suggesting their potential involvement as possible prognostic factors to predict therapy response and as therapeutic targets in combination with usual therapy.
Collapse
Affiliation(s)
- Maria Chiara Ciferri
- Department of Experimental Medicine (DIMES), University of Genova, Genova 16132, Italy
| | - Roberta Tasso
- Department of Experimental Medicine (DIMES), University of Genova, Genova 16132, Italy
- Dipartimento della Ricerca, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy
| |
Collapse
|
26
|
He GD, Sun S, Huang YQ. Association of Circulating, Inflammatory Response Exosomal Long RNAs with Ischemic Stroke. FRONT BIOSCI-LANDMRK 2025; 30:25355. [PMID: 40018923 DOI: 10.31083/fbl25355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 09/07/2024] [Accepted: 09/19/2024] [Indexed: 03/01/2025]
Abstract
BACKGROUND The expression profiles and function of exosomal long RNAs (exoLRs) in ischemic stroke remain unknown. This study aimed to investigate the pathophysiologic responses reflected by exoLRs. METHODS The expression profile of exosomal messenger RNA, long non-coding RNA and circular RNA in 9 patients with ischemic stroke and 12 healthy individuals were analyzed by sequencing. We assessed the immune cell landscape to reveal the pathophysiologic responses reflected by exoLRs and performed biological process and pathway enrichment analyses. Competing endogenous RNA networks were constructed to explore the molecular functions of exoLRs. RESULTS A total of 321 up- and 187 down-regulated messenger RNAs, 31 up- and 9 down-regulated long non-coding RNAs, and 67 up- and 48 down-regulated circular RNAs were identified. The immune cell landscape analysis identified that the proportions of exhausted and gamma delta T cells were statistically higher in patients with ischemic stroke. Bioinformatics analyses, including enrichment and competing endogenous RNA network analyses, also indicated that exoLRs were associated with T- cell-mediated inflammatory responses. CONCLUSIONS The expression patterns of exoLRs highlighted the association between ischemic stroke and inflammatory responses mediated by T cells.
Collapse
Affiliation(s)
- Guo-Dong He
- Department of Cardiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 510080 Guangzhou, Guangdong, China
- Institute of Medical Research, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 510080 Guangzhou, Guangdong, China
| | - Shuo Sun
- Department of Cardiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 510080 Guangzhou, Guangdong, China
| | - Yu-Qing Huang
- Department of Cardiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 510080 Guangzhou, Guangdong, China
| |
Collapse
|
27
|
Aires I, Parada B, Ferreira R, Oliveira PA. Recent animal models of bladder cancer and their application in drug discovery: an update of the literature. Expert Opin Drug Discov 2025:1-21. [PMID: 39954010 DOI: 10.1080/17460441.2025.2465373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 12/29/2024] [Accepted: 02/07/2025] [Indexed: 02/17/2025]
Abstract
INTRODUCTION Bladder cancer presents a significant health problem worldwide, with environmental and genetic factors contributing to its incidence. Histologically, it can be classified as carcinoma in situ, non-muscle invasive and muscle-invasive carcinoma, each one with distinct genetic alterations impacting prognosis and response to therapy. While traditional transurethral resection is commonly performed in carcinoma in situ and non-muscle invasive carcinoma, it often fails to prevent recurrence or progression to more aggressive phenotypes, leading to the frequent need for additional treatment such as intravesical chemotherapy or immunotherapy. Despite the advances made in recent years, treatment options for bladder cancer are still lacking due to the complex nature of this disease. So, animal models may hold potential for addressing these limitations, because they not only allow the study of disease progression but also the evaluation of therapies and the investigation of drug repositioning. AREAS COVERED This review discusses the use of animal models over the past decade, highlighting key discoveries and discussing advantages and disadvantages for new drug discovery. EXPERT OPINION Over the past decade animal models have been employed to evaluate new mechanisms underlying the responses to standard therapies, aiming to optimize bladder cancer treatment. The authors propose that molecular engineering techniques and AI may hold promise for the future development of more precise and effective targeted therapies in bladder cancer.
Collapse
Affiliation(s)
- Inês Aires
- Department of Chemistry, University of Aveiro, Aveiro, Portugal
- Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal
| | - Belmiro Parada
- Coimbra Institute for Clinical and Biomedical, University of Coimbra, Coimbra, Portugal
| | - Rita Ferreira
- Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Paula A Oliveira
- Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal
| |
Collapse
|
28
|
Lv C, Chen J, Wang Y, Lin Y. Immunoregulatory role of exosomal circRNAs in the tumor microenvironment. Front Oncol 2025; 15:1453786. [PMID: 40034598 PMCID: PMC11872884 DOI: 10.3389/fonc.2025.1453786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 01/02/2025] [Indexed: 03/05/2025] Open
Abstract
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.
Collapse
Affiliation(s)
- Cunming Lv
- College of Basic Medical Sciences, China Three Gorges University, Yichang, China
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
| | - Jinhao Chen
- College of Basic Medical Sciences, China Three Gorges University, Yichang, China
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China
| | - Yuxiang Wang
- College of Electrical Engineering and New Energy, China Three Gorges University, Yichang, China
| | - Yichen Lin
- Department of Medicine, Ningbo University, Ningbo, China
| |
Collapse
|
29
|
Huang H, Jiang NN, Lu GW, Xu F, Sun LL, Zhu J, Dong Z, Zhang ZJ, Liu S. CircMETTL9 targets CCAR2 to induce neuronal oxidative stress and apoptosis via mitochondria-mediated pathways following traumatic brain injury. Free Radic Biol Med 2025; 228:44-61. [PMID: 39709098 DOI: 10.1016/j.freeradbiomed.2024.12.041] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/18/2024] [Accepted: 12/19/2024] [Indexed: 12/23/2024]
Abstract
Traumatic brain injury (TBI) remains a principal factor in neurological disorders, often resulting in significant morbidity due to secondary neuroinflammatory and oxidative stress responses. While circular RNAs are recognized for their high expression levels in the nervous system and play crucial roles in various neurological processes, their specific contributions to the pathophysiology of TBI remain underexplored. In this study, the possible molecular mechanisms through which circMETTL9 modulated oxidative stress and neurological outcomes following TBI were investigated. In vitro model of oxidative stress utilizing SH-SY5Y cells revealed that circMETTL9 knockdown significantly attenuated H₂O₂-induced reactive oxygen species (ROS) production, reduced apoptosis, and preserved mitochondrial function. Additionally, CCAR2 has been identified as a circMETTL9-binding protein by mass spectrometry and RNA immunoprecipitation, with circMETTL9 positively regulating CCAR2 expression. Meanwhile, on the basis of silencing CCAR2, it was verified that the regulation of oxidative stress in SH-SY5Y cells by circMETTL9 was mediated by CCAR2. In vivo experiments using a TBI rat model further confirmed that CCAR2 knockdown alleviated central nervous system (CNS) injury, reduced oxidative stress and apoptosis, and protected mitochondrial integrity following TBI. These findings suggest a novel mechanism by which circMETTL9 targets CCAR2 via mitochondria-mediated Bax/Bcl-2/caspase-3 signaling to regulate apoptosis. CircMETTL9 may provide a viable therapeutic target for mitigating neurological dysfunction following TBI, offering new insights into potential interventions aimed at reducing secondary brain injury.
Collapse
Affiliation(s)
- Hao Huang
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China; School of Nursing and Rehabilitation, Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Nan-Nan Jiang
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China; School of Nursing and Rehabilitation, Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Gui-Wei Lu
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China; School of Nursing and Rehabilitation, Nantong University, Nantong, 226001, Jiangsu Province, China; Department of Rehabilitation Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu Province, China
| | - Feng Xu
- The Second People's Hospital of Nantong, Nantong, 226002, Jiangsu Province, China
| | - Lu-Lu Sun
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Jing Zhu
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China
| | - Zhao Dong
- Nanjing Vocational Health College, Nanjing, 210038, Jiangsu Province, China.
| | - Zhi-Jun Zhang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, 226001, Jiangsu Province, China.
| | - Su Liu
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
| |
Collapse
|
30
|
Zhang G, Wu X, Fu H, Sun D. Circular RNA microarray expression profile and potential function of circDOCK1 in colorectal cancer. Front Genet 2025; 16:1443876. [PMID: 39967686 PMCID: PMC11832710 DOI: 10.3389/fgene.2025.1443876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
Introduction Endoscopic tissue biopsy combined with histopathology is the gold standard for the diagnosis of colorectal cancer (CRC); however, the invasive nature of this procedure hinders its acceptance by patients. Therefore, there exists a critical need to identify novel markers facilitating early CRC detection and prognosis. Circular RNAs (circRNAs) hold promise as novel clinical diagnostic markers. This study aimed to investigate the impact of circDOCK1 on CRC metastasis and prognosis as well as its underlying molecular mechanisms. Methods We explored circRNA expression profiles in four pairs of CRC tissues and adjacent non-carcinoma tissues via microarray analysis. After Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and circRNA-miRNA network analyses, circDOCK1 was chosen for further investigation. We evaluated its clinical relevance in 80 CRC tissue pairs and adjacent controls, correlating circDOCK1 expression with clinical characteristics. Follow-up data from patient telephone interviews were analyzed for survival outcomes. Transfection efficiency was confirmed via qRT-PCR in HCT116 and SW480 colon cells, and the effects of circDOCK1 on cell proliferation, migration, and invasion were assessed. Results Microarray data revealed 149 significantly differentially expressed circRNAs, including 71 upregulated and 78 downregulated circRNAs, in CRC tissues. CircDOCK1 exhibited elevated expression in patients with CRC and emerged as an independent prognostic factor. Kaplan-Meier curve analysis suggested that circDOCK1 expression is an unfavorable prognostic factor in patients with CRC. In vivo experiments revealed that circDOCK1 overexpression enhanced the proliferation, migration, and invasion of CRC cells, with consistent results upon circDOCK1 downregulation. Conclusion These data indicate that circDOCK1 may play a role in promoting the proliferation, migration, and invasion of CRC cells, suggesting its potential as a CRC biomarker.
Collapse
Affiliation(s)
| | | | | | - Daqing Sun
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, China
| |
Collapse
|
31
|
Guo Y, Huang Q, Heng Y, Zhou Y, Chen H, Xu C, Wu C, Tao L, Zhou L. Circular RNAs in cancer. MedComm (Beijing) 2025; 6:e70079. [PMID: 39901896 PMCID: PMC11788016 DOI: 10.1002/mco2.70079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 12/23/2024] [Accepted: 01/09/2025] [Indexed: 02/05/2025] Open
Abstract
Circular RNA (circRNA), a subtype of noncoding RNA, has emerged as a significant focus in RNA research due to its distinctive covalently closed loop structure. CircRNAs play pivotal roles in diverse physiological and pathological processes, functioning through mechanisms such as miRNAs or proteins sponging, regulation of splicing and gene expression, and serving as translation templates, particularly in the context of various cancers. The hallmarks of cancer comprise functional capabilities acquired during carcinogenesis and tumor progression, providing a conceptual framework that elucidates the nature of the malignant transformation. Although numerous studies have elucidated the role of circRNAs in the hallmarks of cancers, their functions in the development of chemoradiotherapy resistance remain unexplored and the clinical applications of circRNA-based translational therapeutics are still in their infancy. This review provides a comprehensive overview of circRNAs, covering their biogenesis, unique characteristics, functions, and turnover mechanisms. We also summarize the involvement of circRNAs in cancer hallmarks and their clinical relevance as biomarkers and therapeutic targets, especially in thyroid cancer (TC). Considering the potential of circRNAs as biomarkers and the fascination of circRNA-based therapeutics, the "Ying-Yang" dynamic regulations of circRNAs in TC warrant vastly dedicated investigations.
Collapse
Affiliation(s)
- Yang Guo
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Qiang Huang
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Yu Heng
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Yujuan Zhou
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Hui Chen
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Chengzhi Xu
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Chunping Wu
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Lei Tao
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Liang Zhou
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| |
Collapse
|
32
|
Zhang X, Tan Y, He X, Huang J, Ni X, Hu Q, Cai J. The diagnostic accuracy of exosomes for glioma: A meta-analysis. BIOMOLECULES & BIOMEDICINE 2025; 25:541-552. [PMID: 39465690 PMCID: PMC12010979 DOI: 10.17305/bb.2024.11268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 10/17/2024] [Accepted: 10/17/2024] [Indexed: 10/29/2024]
Abstract
Glioma is one of the most prevalent primary intracranial tumors, and biomarker testing offers a non-invasive modality with high diagnostic efficiency. The aim of this meta-analysis is to evaluate the diagnostic effectiveness of exosomes as biomarkers for glioma. We included 16 studies on exosomes as biomarkers for gliomas. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for 25 biomarkers across these 16 studies were as follows: 82% (95% CI: 0.77-0.86), 91% (95% CI: 0.86-0.94), 9.10 (95% CI: 5.64-14.68), 0.20 (95% CI: 0.16-0.25), 45.94 (95% CI: 25.40-83.09), and 0.92 (95% CI: 0.89-0.94), respectively. Meta-regression indicated that biomarker analysis, biomarker type, and sample size may be sources of heterogeneity. Subgroup analysis suggested that ultracentrifugation (UC) was a better method for extracting exosomes. miRNA and other RNA groups (sncRNA, lncRNA, circRNA) provided higher SEN (0.88 vs. 0.84 vs. 0.78) compared to proteins. This study demonstrates the superior diagnostic efficacy of exosomes as biomarkers for gliomas, with high accuracy in diagnosing gliomas.
Collapse
Affiliation(s)
- XiangMin Zhang
- Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, China
| | - YanDi Tan
- Department of Ultrasound, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - XiaoYa He
- Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Jie Huang
- Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, China
| | - XiaoYing Ni
- Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, China
| | - Qian Hu
- Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, China
| | - JinHua Cai
- Department of Radiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, China
| |
Collapse
|
33
|
Li G, Chen H, Shen J, Ding Y, Chen J, Zhang Y, Tang M, Xu N, Fang Y. Unveiling new therapeutic horizons in rheumatoid arthritis: an In-depth exploration of circular RNAs derived from plasma exosomes. J Orthop Surg Res 2025; 20:109. [PMID: 39881399 PMCID: PMC11776339 DOI: 10.1186/s13018-025-05494-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/13/2025] [Indexed: 01/31/2025] Open
Abstract
Rheumatoid arthritis (RA), a chronic inflammatory joint disease causing permanent disability, involves exosomes, nanosized mammalian extracellular particles. Circular RNA (circRNA) serves as a biomarker in RA blood samples. This research screened differentially expressed circRNAs in RA patient plasma exosomes for novel diagnostic biomarkers. In this study, samples of RA patients with insufficient response to methotrexate (MTX-IR), combined use of tumor necrosis factor inhibitors (TNFi) were followed up for half a year, and 56 circRNA samples of self-test data were stratified into training, testing, and external validation cohorts according to whether American College of Rheumatology 20% improvement criteria (ACR20) was achieved. A diagnostic xgboost model was developed using common hub genes identified by random forest and least absolute shrinkage and selection operator (LASSO), with intersection genes derived from overlapping machine learning-selected genes. Diagnostic performance evaluated via receiver operating characteristic (ROC) curves using pROC for area under the curve (AUC). Optimal LASSO model with 4 circRNAs determined, with AUC > 0.6 for key genes. The model validation performed well on the test set, but not significantly on the validation set. Then, circRNA screening was performed in combination with clinical data, and cross-validation identified hsa-circ0002715, hsa-circ0001946, hsa-circ0000836, and rheumatoid factor (RF) as key genes, among which hsa-circ0002715 and hsa-circ0001946 were emphasized as key markers on the training set. In addition, the morphology and size of exosomes and the expression of CD9 and CD81 verified the successful extraction of exosomes. The qPCR analysis of plasma exosomes in TNFi patients found that the expression of hsa-circ0002715 was higher than that in patients who didn't reach ACR20, and the expression of hsa-circ0001946 was lower than that in patients who didn't reach ACR20. The above studies suggested that hsa-circ0002715 and hsa-circ0001946 may become markers for predicting MTX-IR RA patients and TNFi precision treatment.
Collapse
Affiliation(s)
- Guoqing Li
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Hongyi Chen
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Jiacheng Shen
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Yimin Ding
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Jingqiong Chen
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Yongbin Zhang
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Mingrui Tang
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Nan Xu
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China
| | - Yuxuan Fang
- Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, Jiangsu, 225000, China.
| |
Collapse
|
34
|
Karimi R, Javandoost E, Asadmasjedi N, Atashi A, Soleimani A, Behzadifard M. Circular RNAs: history, metabolism, mechanisms of function, and regulatory roles at a glance. Ann Med Surg (Lond) 2025; 87:141-150. [PMID: 40109602 PMCID: PMC11918698 DOI: 10.1097/ms9.0000000000002761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 11/05/2024] [Indexed: 03/22/2025] Open
Abstract
Circular RNAs (circRNAs) are non-coding RNA (ncRNA) molecules that, due to their covalent ring structure and lack of free ends, have a very high intracellular stability compared to their linear counterparts. In general, circRNAs are expressed in mammalian cells and exhibit tissue/cell-specific expression patterns. Mounting evidence is indicative that circRNAs regulate a variety of cellular processes by acting as miRNA sponges, transcriptional regulators, protein sponges, molecular scaffolds, and protein/peptide translators. The emergence of the biological functions of circRNAs has brought a novel outlook to our better understanding of cellular physiology and disease pathogenesis. CircRNAs have also been shown to play a critical role in the occurrence, development and progression of cancers. Their participation in the pathophysiology of various diseases including cardiovascular diseases, diabetes and neurological disorders is very important. Such characteristics have led to more studies investigating circRNAs as promising tools in molecular medicine and targeted therapy.
Collapse
Affiliation(s)
- Roqaye Karimi
- Department of Hematology and Cell Therapy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ehsan Javandoost
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Nooshin Asadmasjedi
- Department of Laboratory Sciences, School of Allied Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Amir Atashi
- Stem cell and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Alireza Soleimani
- Student Research Committee Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mahin Behzadifard
- Department of Laboratory Sciences, School of Allied Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| |
Collapse
|
35
|
Schaft N, Dörrie J. The Role of Non-coding RNAs in Tumorigenesis, Diagnosis/Prognosis, and Therapeutic Strategies for Cutaneous Melanoma. Methods Mol Biol 2025; 2883:79-107. [PMID: 39702705 DOI: 10.1007/978-1-0716-4290-0_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2024]
Abstract
RNA is a substance with various biological functions. It serves as blueprint for proteins and shuttles information from the genes to the protein factories of the cells. However, these factories-the ribosomes-are also composed mainly of RNA, whose purpose is not storing information but enzymatic action. In addition, there is a cornucopia of RNA molecules within our cells that form a complex regulatory network, connected with all aspects of cellular development and maintenance. These non-coding RNAs can be used for diagnostics and therapeutic strategies in cancer. In this chapter we give an overview of recent developments in non-coding RNA-based diagnostics and therapies for cutaneous melanoma. It is not meant to be comprehensive; however, it describes examples based on some of the most recent publications in this field.
Collapse
Affiliation(s)
- Niels Schaft
- Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, CCC WERA, Comprehensive Cancer Center Erlangen European Metropolitan Area of Nuremberg (CCC ER-EMN), Deutsches Zentrum Immuntherapie (DZI), Bavarian Cancer Research Center (BZKF), Erlangen, Germany.
| | - Jan Dörrie
- Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, CCC WERA, Comprehensive Cancer Center Erlangen European Metropolitan Area of Nuremberg (CCC ER-EMN), Deutsches Zentrum Immuntherapie (DZI), Bavarian Cancer Research Center (BZKF), Erlangen, Germany
| |
Collapse
|
36
|
Hashimoto K, Ochiya T, Shimomura A. Liquid biopsy using non-coding RNAs and extracellular vesicles for breast cancer management. Breast Cancer 2025; 32:16-25. [PMID: 38512533 DOI: 10.1007/s12282-024-01562-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 02/24/2024] [Indexed: 03/23/2024]
Abstract
This article examines liquid biopsy using non-coding RNAs and extracellular vesicles in detail. Liquid biopsy is emerging as a prominent non-invasive diagnostic tool in the treatment of breast cancer. We will elucidate the roles of these molecules in early detection, monitoring treatment effectiveness, and prognostic assessment of breast cancer. Additionally, the clinical significance of these molecules will be discussed. We aim to delve into the distinct characteristics of these molecules and their possible roles in breast cancer management, with an anticipation of their contribution to future diagnostic and therapeutic advancements.
Collapse
Affiliation(s)
- Kazuki Hashimoto
- Department of Breast Surgical Oncology, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Takahiro Ochiya
- Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Akihiko Shimomura
- Department of Breast and Medical Oncology, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan.
| |
Collapse
|
37
|
Wu S, Hu Y, Lei X, Yang X. The Emerging Roles of CircPVT1 in Cancer Progression. Curr Pharm Biotechnol 2025; 26:1-8. [PMID: 38454774 DOI: 10.2174/0113892010282141240226112253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 01/27/2024] [Accepted: 02/15/2024] [Indexed: 03/09/2024]
Abstract
CircRNA is stable due to its ring structure and is abundant in humans, which not only exists in various tissues and biofluids steadily but also plays a significant role in the physiology and pathology of human beings. CircPVT1, an endogenous circRNA, has recently been identified from the PVT1 gene located in the cancer risk region 8q24. CircPVT1 is reported to be highly expressed in many different tumors, where it affects tumor cell proliferation, apoptosis, invasion, and migration. We summarize the biosynthesis and biological functions of circPVT1 and analyze the relationship between circPVT1 and tumors as well as its significance to tumors. Further, it's noteworthy for the diagnosis, treatment, and prognosis of cancer patients. Therefore, circPVT1 is likely to become an innovative tumor marker.
Collapse
Affiliation(s)
- Shijie Wu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Yan Hu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Xiaoyong Lei
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, People's Republic of China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Xiaoyan Yang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, People's Republic of China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| |
Collapse
|
38
|
Ebrahimi F, Kumari A, Ghadami S, Al Abdullah S, Dellinger K. The Potential for Extracellular Vesicles in Nanomedicine: A Review of Recent Advancements and Challenges Ahead. Adv Biol (Weinh) 2024:e2400623. [PMID: 39739455 DOI: 10.1002/adbi.202400623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/02/2024] [Indexed: 01/02/2025]
Abstract
Extracellular vesicles (EVs) have emerged as promising tools in diagnostics and therapy for chronic diseases, including cancer and Alzheimer's. Small EVs, also called exosomes, are lipid-bound particles (≈30-150 nm) that play a role in healthy and pathophysiological interactions, including intercellular communication, by transporting bioactive molecules, including proteins, lipids, and nucleic acids. Their ability to cross biological barriers, such as the blood-brain barrier, makes them ideal candidates for targeted therapeutic interventions. In the context of chronic diseases, exosomes can be engineered to deliver active agents, including small molecules and siRNAs to specific target cells, providing a novel approach to precision medicine. Moreover, exosomes show great promise as repositories for diagnostic biomarkers. Their cargo can reflect the physiological and pathological status of the parent cells, making them valuable indicators of disease progression and response to treatment. This paper presents a comprehensive review of the application of exosomes in four chronic diseases: cancer, cardiovascular disease, neurodegenerative disease, and orthopedic disease, which significantly impact global public health due to their high prevalence and associated morbidity and mortality rates. Furthermore, the potential of exosomes as valuable tools for theranostics and disease management is highlighted. Finally, the challenges associated with exosomes and their demonstrated potential for advancing future nanomedicine applications are discussed.
Collapse
Affiliation(s)
- Farbod Ebrahimi
- Department of Nanoengineering, Joint School of Nanoscience and Nanoengineering, North Carolina A&T State University, 2907 E Gate City Blvd, Greensboro, NC, 27401, USA
| | - Anjali Kumari
- Department of Nanoengineering, Joint School of Nanoscience and Nanoengineering, North Carolina A&T State University, 2907 E Gate City Blvd, Greensboro, NC, 27401, USA
| | - Samaneh Ghadami
- Department of Nanoengineering, Joint School of Nanoscience and Nanoengineering, North Carolina A&T State University, 2907 E Gate City Blvd, Greensboro, NC, 27401, USA
| | - Saqer Al Abdullah
- Department of Nanoengineering, Joint School of Nanoscience and Nanoengineering, North Carolina A&T State University, 2907 E Gate City Blvd, Greensboro, NC, 27401, USA
| | - Kristen Dellinger
- Department of Nanoengineering, Joint School of Nanoscience and Nanoengineering, North Carolina A&T State University, 2907 E Gate City Blvd, Greensboro, NC, 27401, USA
| |
Collapse
|
39
|
Song W, Chen X, Wu H, Rahimian N. Circular RNAs as a novel class of potential therapeutic and diagnostic biomarkers in reproductive biology/diseases. Eur J Med Res 2024; 29:643. [PMID: 39741306 DOI: 10.1186/s40001-024-02230-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 12/17/2024] [Indexed: 01/02/2025] Open
Abstract
Infertility is a prevalent problem among 10% of people within their reproductive years. Sometimes, even advanced treatment options like assisted reproduction technology have the potential to result in failed implantation. Because of the expected changes in gene expression during both in vitro and in vivo fertilization processes, these methods of assisting fertility have also been associated with undesirable pregnancy outcomes related to infertility. In this aspect, Circular RNAs (circRNAs) play a crucial role as epigenetic modifiers in a wide range of biological and pathological activities, including problems with fertility. CircRNAs are integral pieces in multiple cellular functions, including moving substances within the nucleus, silencing one X chromosome, cell death, the ability of stem cells to differentiate into different cell types, and the process of gene expression inherited from parental genes. Due to the progress made in high-speed gene sequencing, a large amount of circRNA molecules have been detected, revealing their significant functions in diverse biological functions like enhancing testicular development, preserving the differentiation and renewal of spermatogonial cells, and controlling spermatocyte meiosis. Moreover, these non-coding RNAs contribute in different aspects of female reproductive system including pregnancy-related diseases, gynecologic cancers, and endometriosis. In conclusion, there is no denying that circRNAs have immense potential to be used as biomarkers and treatments for reproductive disorders in males and females. In this research, we provide a comprehensive analysis of the multiple circRNAs associated with women's infertility.
Collapse
Affiliation(s)
- Wanyu Song
- Department of Obstetrics, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China
- People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China
| | - Xiuli Chen
- Department of Obstetrics, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China
- People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China
| | - Haiying Wu
- Department of Obstetrics, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China.
- People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
| | - Neda Rahimian
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
40
|
Zhang L, Fang C, Zhu W, Zhong W, Ye R. Serum Hsa_circ_0023919 is a Predictive Biomarker of Chemoresistance in CRC Treatment. Int J Gen Med 2024; 17:6535-6543. [PMID: 39759896 PMCID: PMC11697668 DOI: 10.2147/ijgm.s482379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 10/23/2024] [Indexed: 01/07/2025] Open
Abstract
Background The diversity of available chemotherapeutic modalities for colorectal cancer (CRC) entails the implementation of personalized therapeutic regimens to optimize patient outcomes. Currently, the clinical use of biological markers for treatment selection is inadequate to achieve individualization. Circulatory RNAs (circRNAs), which function as plasma biomarkers, play a critical role in regulating biological processes in different types of cancer. Methods The samples (serum) were obtained from 80 CRC patients and 80 healthy individuals (controls) to assess the level of hsa_circ_0023919 via qRT-PCR analysis. Results In findings, hsa_circ_0023919 has a positive association with the disease stage and is greatly elevated in chemoresistant CRC patients. In addition, the area under the curve for hsa_circ_0023919 was modest, and an increase in hsa_circ_0023919 expressions was linked with a decreased overall survival (OS) and progression-free survival (PFS). Serum hsa_circ_0023919 levels serve as a diagnostic indicator for chemoresistance in CRC. Conclusion The findings suggested that hsa_circ_0023919 contributes to promoting chemoresistance in CRC patients. Consequently, it can be considered a potent therapeutic target for CRC treatment.
Collapse
Affiliation(s)
- Lei Zhang
- Department of Gastrointestinal Hernia, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China
| | - Chuanfa Fang
- Department of Gastrointestinal Hernia, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China
| | - Weiquan Zhu
- Department of Gastrointestinal Hernia, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China
| | - Wu Zhong
- Department of Gastrointestinal Hernia, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China
| | - Rongqiang Ye
- Department of Hepatobiliary and Pancreatic Surgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China
| |
Collapse
|
41
|
Khanicheragh P, Abbasi-Malati Z, Saghebasl S, Hassanpour P, Milani SZ, Rahbarghazi R, Hasani A. Exosomes and breast cancer angiogenesis; Highlights in intercellular communication. Cancer Cell Int 2024; 24:402. [PMID: 39696346 DOI: 10.1186/s12935-024-03606-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 12/06/2024] [Indexed: 12/20/2024] Open
Abstract
Breast cancer (BC) is a prevalent and highly lethal cancer in females. Like other cancer types, the intricate cellular and molecular heterogeneity leads to the variation of therapeutic outcomes. The development and progression of blood vessels increase the tumor cell expansion and metastasis to remote sites. Based on several pieces of scientific data, different mediators and cells are involved in the promotion of angiogenesis into the tumor parenchyma. Recent data have indicated the critical role of extracellular vesicles, especially exosomes (Exos), in the transfer of angiogenesis molecules between the BC cells. Due to unique physicochemical properties, and the transfer of certain signaling molecules, Exos are at the center of attention in terms of biomarkers and therapeutic bullets in cancer patients. Along with these statements, understanding the modulatory role of Exos in BC angiogenesis seems critical in the clinical setting. Here, the mechanisms by which BC cells can orchestrate the angiogenesis phenomenon via Exos are discussed in detail. The present study can help us to understand the pro-/anti-angiogenesis role of Exos in BC and to design better oncostatic strategies.
Collapse
Affiliation(s)
- Parisa Khanicheragh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, 5165687386, Iran
| | - Zahra Abbasi-Malati
- Student Committee Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Solmaz Saghebasl
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parisa Hassanpour
- Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, 5165687386, Iran
| | - Soheil Zamen Milani
- Student Committee Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Rahbarghazi
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Akbar Hasani
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, 5165687386, Iran.
| |
Collapse
|
42
|
Lou Y, Yan J, Liu Q, Miao M, Shao Y. Biological functions and molecular mechanisms of exosome-derived circular RNAs and their clinical implications in digestive malignancies: the vintage in the bottle. Ann Med 2024; 56:2420861. [PMID: 39484707 PMCID: PMC11536637 DOI: 10.1080/07853890.2024.2420861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 10/05/2024] [Accepted: 10/11/2024] [Indexed: 11/03/2024] Open
Abstract
BACKGROUND 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). MATERIALS AND METHODS We searched recent studies and references to summary the research progress of exosomal circRNA. RESULTS 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. CONCLUSION 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.
Collapse
Affiliation(s)
- Yuanyan Lou
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, China
- Health Science Center, Ningbo University, Ningbo, China
| | - Jianing Yan
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Qingqing Liu
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Min Miao
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Yongfu Shao
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, China
- Health Science Center, Ningbo University, Ningbo, China
| |
Collapse
|
43
|
Miceli RT, Chen T, Nose Y, Tichkule S, Brown B, Fullard JF, Saulsbury MD, Heyliger SO, Gnjatic S, Kyprianou N, Cordon‐Cardo C, Sahoo S, Taioli E, Roussos P, Stolovitzky G, Gonzalez‐Kozlova E, Dogra N. Extracellular vesicles, RNA sequencing, and bioinformatic analyses: Challenges, solutions, and recommendations. J Extracell Vesicles 2024; 13:e70005. [PMID: 39625409 PMCID: PMC11613500 DOI: 10.1002/jev2.70005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 09/20/2024] [Accepted: 10/07/2024] [Indexed: 12/06/2024] Open
Abstract
Extracellular vesicles (EVs) are heterogeneous entities secreted by cells into their microenvironment and systemic circulation. Circulating EVs carry functional small RNAs and other molecular footprints from their cell of origin, and thus have evident applications in liquid biopsy, therapeutics, and intercellular communication. Yet, the complete transcriptomic landscape of EVs is poorly characterized due to critical limitations including variable protocols used for EV-RNA extraction, quality control, cDNA library preparation, sequencing technologies, and bioinformatic analyses. Consequently, there is a gap in knowledge and the need for a standardized approach in delineating EV-RNAs. Here, we address these gaps by describing the following points by (1) focusing on the large canopy of the EVs and particles (EVPs), which includes, but not limited to - exosomes and other large and small EVs, lipoproteins, exomeres/supermeres, mitochondrial-derived vesicles, RNA binding proteins, and cell-free DNA/RNA/proteins; (2) examining the potential functional roles and biogenesis of EVPs; (3) discussing various transcriptomic methods and technologies used in uncovering the cargoes of EVPs; (4) presenting a comprehensive list of RNA subtypes reported in EVPs; (5) describing different EV-RNA databases and resources specific to EV-RNA species; (6) reviewing established bioinformatics pipelines and novel strategies for reproducible EV transcriptomics analyses; (7) emphasizing the significant need for a gold standard approach in identifying EV-RNAs across studies; (8) and finally, we highlight current challenges, discuss possible solutions, and present recommendations for robust and reproducible analyses of EVP-associated small RNAs. Overall, we seek to provide clarity on the transcriptomics landscape, sequencing technologies, and bioinformatic analyses of EVP-RNAs. Detailed portrayal of the current state of EVP transcriptomics will lead to a better understanding of how the RNA cargo of EVPs can be used in modern and targeted diagnostics and therapeutics. For the inclusion of different particles discussed in this article, we use the terms large/small EVs, non-vesicular extracellular particles (NVEPs), EPs and EVPs as defined in MISEV guidelines by the International Society of Extracellular Vesicles (ISEV).
Collapse
Affiliation(s)
- Rebecca T. Miceli
- Department of Pathology, Molecular and Cell‐Based MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Tzu‐Yi Chen
- Department of Pathology, Molecular and Cell‐Based MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Yohei Nose
- Department of ImmunologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Oncological SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Swapnil Tichkule
- Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Briana Brown
- Department of Pathology, Molecular and Cell‐Based MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - John F. Fullard
- Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Genetics and Genomics SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Center for Disease Neurogenetics, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Friedman Brain Institute, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Marilyn D. Saulsbury
- Department of Pharmaceutical Sciences, School of PharmacyHampton UniversityHamptonVirginiaUSA
| | - Simon O. Heyliger
- Department of Pharmaceutical Sciences, School of PharmacyHampton UniversityHamptonVirginiaUSA
| | - Sacha Gnjatic
- Department of ImmunologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Oncological SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Natasha Kyprianou
- Department of Pathology, Molecular and Cell‐Based MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Oncological SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of UrologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Carlos Cordon‐Cardo
- Department of Pathology, Molecular and Cell‐Based MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Susmita Sahoo
- Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Cardiovascular Research Institute, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Emanuela Taioli
- Department of Population Health and ScienceIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Thoracic SurgeryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Panos Roussos
- Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Genetics and Genomics SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Center for Disease Neurogenetics, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Friedman Brain Institute, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Center for Precision Medicine and Translational TherapeuticsJames J. Peters VA Medicinal CenterBronxNew YorkUSA
- Mental Illness Research Education and Clinical Center (MIRECC)James J. Peters VA Medicinal CenterBronxNew YorkUSA
| | - Gustavo Stolovitzky
- Department of Genetics and Genomics SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Biomedical Data Sciences Hub (Bio‐DaSH), Department of Pathology, NYU Grossman School of MedicineNew YorkNew YorkUSA
| | - Edgar Gonzalez‐Kozlova
- Department of ImmunologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Oncological SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Navneet Dogra
- Department of Pathology, Molecular and Cell‐Based MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Department of Genetics and Genomics SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Icahn Genomics Institute, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- AI and Human HealthIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| |
Collapse
|
44
|
Li Y, Tang X, Wang B, Chen M, Zheng J, Chang K. Current landscape of exosomal non-coding RNAs in prostate cancer: Modulators and biomarkers. Noncoding RNA Res 2024; 9:1351-1362. [PMID: 39247145 PMCID: PMC11380467 DOI: 10.1016/j.ncrna.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 06/12/2024] [Accepted: 07/18/2024] [Indexed: 09/10/2024] Open
Abstract
Prostate cancer (PCa) has the highest frequency of diagnosis among solid tumors and ranks second as the primary cause of cancer-related deaths. Non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs and circular RNAs, frequently exhibit dysregulation and substantially impact the biological behavior of PCa. Compared with circulating ncRNAs, ncRNAs loaded into exosomes are more stable because of protection by the lipid bilayer. Furthermore, exosomal ncRNAs facilitate the intercellular transfer of molecules and information. Increasing evidence suggests that exosomal ncRNAs hold promising potential in the progression, diagnosis and prognosis of PCa. This review aims to discuss the functions of exosomal ncRNAs in PCa, evaluate their possible applications as clinical biomarkers and therapeutic targets, and provide a comprehensive overview of the ncRNAs regulatory network in PCa. We also identified ncRNAs that can be utilized as biomarkers for diagnosis, staging, grading and prognosis assessment in PCa. This review offers researchers a fresh perspective on the functions of exosomal ncRNAs in PCa and provides additional options for its diagnosis, progression monitoring, and prognostic prediction.
Collapse
Affiliation(s)
- Yongxing Li
- Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, PR China
- School of Medicine, Chongqing University, Chongqing, 400030, PR China
| | - Xiaoqi Tang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China
| | - Binpan Wang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China
| | - Ming Chen
- Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China
| | - Ji Zheng
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, PR China
- School of Medicine, Chongqing University, Chongqing, 400030, PR China
- State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China
| | - Kai Chang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China
- State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China
| |
Collapse
|
45
|
Almouh M, Soukkarieh C, Kassouha M, Ibrahim S. Crosstalk between circular RNAs and the STAT3 signaling pathway in human cancer. BIOCHIMICA ET BIOPHYSICA ACTA. GENE REGULATORY MECHANISMS 2024; 1867:195051. [PMID: 39121909 DOI: 10.1016/j.bbagrm.2024.195051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 07/31/2024] [Accepted: 08/05/2024] [Indexed: 08/12/2024]
Abstract
Circular RNAs (circRNAs) are endogenous covalently closed single-stranded RNAs produced by reverse splicing of pre-mRNA. Emerging evidence suggests that circRNAs contribute to cancer progression by modulating the oncogenic STAT3 signaling pathway, which plays key roles in human malignancies. STAT3 signaling-related circRNAs expression appears to be extensively dysregulated in diverse cancer types, where they function either as tumor suppressors or oncogenes. However, the biological effects of STAT3 signaling-related circRNAs and their associations with cancer have not been systematically studied before. Given this, shedding light on the interaction between circRNAs and STAT3 signaling pathway in human malignancies may provide several novel insights into cancer therapy. In this review, we provide a comprehensive introduction to the molecular mechanisms by which circRNAs regulate STAT3 signaling in cancer progression, and the crosstalk between STAT3 signaling-related circRNAs and other signaling pathways. We also further discuss the role of the circRNA/STAT3 axis in cancer chemotherapy sensitivity.
Collapse
Affiliation(s)
- Mansour Almouh
- Department of Animal Production, Faculty of Veterinary Medicine, Hama University, Hama, Syria.
| | - Chadi Soukkarieh
- Department of Animal Biology, Faculty of Sciences, Damascus University, Damascus, Syria
| | - Morshed Kassouha
- Department of Microbiology, Faculty of Veterinary Medicine, Hama University, Hama, Syria
| | - Samer Ibrahim
- Department of Microbiology, Faculty of Veterinary Medicine, Hama University, Hama, Syria; Faculty of Dentistry, Arab Private University of science and Technology, Hama, Syria
| |
Collapse
|
46
|
Wang MH, Liu ZH, Zhang HX, Liu HC, Ma LH. Hsa_circRNA_000166 accelerates breast cancer progression via the regulation of the miR-326/ELK1 and miR-330-5p/ELK1 axes. Ann Med 2024; 56:2424515. [PMID: 39529543 PMCID: PMC11559033 DOI: 10.1080/07853890.2024.2424515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 07/18/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024] Open
Abstract
PURPOSES To probe the expression, clinical significance, roles, and molecular mechanisms of circRNA_000166 in breast cancer (BC). METHODS Clinical tissue samples were gathered from 84 BC patients who underwent surgery at the Affiliated Hospital of Chengde Medical College. Clinical data were obtained from medical records and postoperative follow-up. Expression levels of circRNA_000166, miR-326, miR-330-5p, and ELK1 mRNA in BC tissues and cells were measured by qRT-PCR, and ELK1 protein levels were assessed by WB. Pearson's correlation analysis evaluated the interrelationships between these RNAs in clinical samples. Luciferase reporter assays verified the interactions between miR-326/miR-330-5p and circRNA_000166, as well as between miR-326/miR-330-5p and ELK1. Cell proliferation, migration, and apoptosis were examined using CCK-8, colony formation, transwell, and flow cytometry assays, respectively. RESULTS CircRNA_000166 was highly expressed in BC tissues and inversely correlated with miR-326/miR-330-5p levels but positively with ELK1 mRNA levels. ELK1 mRNA also inversely associated with miR-326/miR-330-5p levels in BC tissues. Importantly, our findings demonstrated that circRNA_000166 targets miR-326 and miR-330-5p, while ELK1 is the target of miR-326 and miR-330-5p in BC cells. CircRNA_000166 levels positively correlated with tumour size, TNM stage, histological grade, and lymph node metastasis, and negatively associated with postoperative progression-free survival (PFS) and overall survival (OS) in BC patients. CircRNA_000166 was also highly expressed in BC cells, and knockdown of circRNA_000166 reduced proliferation and migration, and increased apoptosis via miR-326/ELK1 and miR-330-5p/ELK1 pathways in vitro. CONCLUSION CircRNA_000166 enhances BC progression through miR-326/ELK1 and miR-330-5p/ELK1 pathways and shows potential as a biomarker for BC diagnosis and treatment.
Collapse
Affiliation(s)
- Ming-Hui Wang
- Department of Breast Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China
| | - Zi-Hui Liu
- Department of Pathology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China
| | - Hong-Xu Zhang
- Department of Breast Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China
| | - Han-Cheng Liu
- Department of Breast Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China
| | - Li-Hui Ma
- Department of Breast Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China
| |
Collapse
|
47
|
Malek Mohammadi M, Rismanchi H, Esmailzadeh S, Farahani A, Hedayati N, Alimohammadi M, Mafi A, Farahani N, Hushmandi K. The emerging role of circular RNAs in cisplatin resistance in ovarian cancer: From molecular mechanism to future potential. Noncoding RNA Res 2024; 9:1280-1291. [PMID: 39040815 PMCID: PMC11261309 DOI: 10.1016/j.ncrna.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 05/05/2024] [Accepted: 05/19/2024] [Indexed: 07/24/2024] Open
Abstract
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.
Collapse
Affiliation(s)
| | - Hamidreza Rismanchi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shakiba Esmailzadeh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Aryan Farahani
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Hedayati
- School of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Mafi
- Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Najma Farahani
- Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| |
Collapse
|
48
|
Wang T, Du Y, Song H, Sun J, Jiang W, Xu Z. hsa_circ_0072309 Inhibits Oncogenesis in Hepatocellular Carcinoma by Epigenetic Activation of its Host Gene. Cell Biochem Biophys 2024; 82:3251-3263. [PMID: 39283585 DOI: 10.1007/s12013-024-01330-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2024] [Indexed: 11/20/2024]
Abstract
Recently, numerous studies have revealed the participation of circular RNAs (circRNAs) in cancer progression. Likewise, this research focused on circRNAs in hepatocellular carcinoma (HCC). A lowly expressed circRNA hsa_circ_0072309 in HCC was screened by analyzing the circRNA microarray GSE242797 and GSE216115 and identified in clinical specimens and cells. Subsequently, CCK-8, colony formation, and transwell assays were performed. The results revealed that hsa_circ_0072309 overexpression suppressed HCC cell proliferation, migration, invasion, and sorafenib resistance, whereas its suppression showed opposite results. Mechanistic investigation found an interaction between hsa_circ_0072309 and its host gene leukemia inhibitory factor receptor (LIFR) in HCC. We found that LIFR overexpression promoted the hsa_circ_0072309 formation. In turn, hsa_circ_0072309 recruited the E1A binding protein p300 to promote the enrichment of H3K27 acetylation (H3K27ac) in the LIFR enhancer, thus transcriptionally promoting LIFR expression. To conclude, we revealed a hsa_circ_0072309/LIFR regulatory loop in HCC, which may provide a potential target for HCC treatment.
Collapse
Affiliation(s)
- Tao Wang
- Department of Interventional Therapy, Yantai Yuhuangding Hospital, NO.20 East Yuhuangding Road, 264000, Yantai, China
| | - Yanan Du
- Nuclear Medicine Department, Yantai Yuhuangding Hospital, NO.20 East Yuhuangding Road, 264000, Yantai, China
| | - Haiyang Song
- Department of Interventional Therapy, Yantai Yuhuangding Hospital, NO.20 East Yuhuangding Road, 264000, Yantai, China
| | - Jiewei Sun
- Nuclear Medicine Department, Yantai Yuhuangding Hospital, NO.20 East Yuhuangding Road, 264000, Yantai, China
| | - Wenjin Jiang
- Department of Interventional Therapy, Yantai Yuhuangding Hospital, NO.20 East Yuhuangding Road, 264000, Yantai, China.
| | - Zhiying Xu
- Nuclear Medicine Department, Yantai Yuhuangding Hospital, NO.20 East Yuhuangding Road, 264000, Yantai, China.
| |
Collapse
|
49
|
Yin D, Zhai X, Feng X, Hua M, Liu J, Chen Y. Circ_0060927 promotes colorectal cancer development by sponging miR-331-3p and upregulating TBX2. Pathol Res Pract 2024; 264:155673. [PMID: 39486250 DOI: 10.1016/j.prp.2024.155673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 09/13/2024] [Accepted: 10/23/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND The dysregulation of circular RNAs (circRNAs) is closely associated with the pathogenesis of colorectal cancer (CRC). The present study aimed to elucidate the biological function and mechanism of circ_0060927 in CRC. METHODS 5-ethynyl-2'-deoxyuridine, Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, as well as Xenograft tumor models were adopted for in vitro and in vivo analyses. The interaction between microRNA-331-3p (miR-331-3p) and circ_0060927 or T-box transcription factor 2 (TBX2) was verified by the dual-luciferase reporter and RNA pull-down assays. RESULTS Circ_0060927 deficiency inhibited cell proliferation, autophagy, migration, and invasion and increased cell apoptosis and necrosis in CRC cells, as well as inhibited tumor growth in vivo. Circ_0060927 could bind to miR-331-3p, and circ_0060927 regulated CRC cell behaviors via sponging miR-331-3p. TBX2 was targeted by miR-331-3p, and miR-331-3p targeted TBX2 to exert the anti-cancer role in CRC cells. Mechanically, circ_0060927 regulated TBX2 expression by sequestering miR-331-3p in CRC cells. CONCLUSION Circ_0060927 downregulation inhibited CRC progression by regulating the miR-331-3p/TBX2 axis, which might offer a potential treatment target for CRC.
Collapse
Affiliation(s)
- Dian Yin
- Department of Oncology, Nantong First People's Hospital and Second Affiliated Hospital of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu, China
| | - XiaoLu Zhai
- Department of Oncology, Nantong First People's Hospital and Second Affiliated Hospital of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu, China
| | - Xiu Feng
- Department of Oncology, Nantong First People's Hospital and Second Affiliated Hospital of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu, China
| | - Mei Hua
- Department of Oncology, Nantong First People's Hospital and Second Affiliated Hospital of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu, China
| | - Jing Liu
- Department of Oncology, Nantong First People's Hospital and Second Affiliated Hospital of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu, China
| | - Ying Chen
- Department of Oncology, Nantong First People's Hospital and Second Affiliated Hospital of Nantong University, 666 Shengli Road, Chongchuan District, Nantong City, Jiangsu, China.
| |
Collapse
|
50
|
Mafi A, Hedayati N, Kahkesh S, Khoshayand S, Alimohammadi M, Farahani N, Hushmandi K. The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways. Noncoding RNA Res 2024; 9:1178-1189. [PMID: 39022676 PMCID: PMC11250881 DOI: 10.1016/j.ncrna.2024.05.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 05/01/2024] [Accepted: 05/20/2024] [Indexed: 07/20/2024] Open
Abstract
As the deadliest type of primary brain tumor, gliomas represent a significant worldwide health concern. Circular RNA (circRNA), a unique non-coding RNA molecule, seems to be one of the most alluring target molecules involved in the pathophysiology of many kinds of cancers. CircRNAs have been identified as prospective targets and biomarkers for the diagnosis and treatment of numerous disorders, particularly malignancies. Recent research has established a clinical link between temozolomide (TMZ) resistance and certain circRNA dysregulations in glioma tumors. CircRNAs may play a therapeutic role in controlling or overcoming TMZ resistance in gliomas and may provide guidance for a novel kind of individualized glioma therapy. To address the biological characteristics of circRNAs and their potential to induce resistance to TMZ, this review has highlighted and summarized the possible roles that circRNAs may play in molecular pathways of drug resistance, including the Ras/Raf/ERK PI3K/Akt signaling pathway and metabolic processes in gliomas.
Collapse
Affiliation(s)
- Alireza Mafi
- Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Neda Hedayati
- School of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Samaneh Kahkesh
- Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Sara Khoshayand
- School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Najma Farahani
- Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| |
Collapse
|