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Chen S, Zhao Q, Zhang R, Liu J, Peng W, Xu H, Li X, Wang X, Wu S, Li G, Nan A. A transcribed ultraconserved noncoding RNA, uc.285+, promotes colorectal cancer proliferation through dual targeting of CDC42 by directly binding mRNA and protein. Transl Res 2024; 270:52-65. [PMID: 38552953 DOI: 10.1016/j.trsl.2024.03.008] [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: 03/26/2023] [Revised: 03/15/2024] [Accepted: 03/24/2024] [Indexed: 04/12/2024]
Abstract
The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC.
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Affiliation(s)
- Sixian Chen
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China
| | - Qingyun Zhao
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China
| | - Ruirui Zhang
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China; School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, PR China
| | - Jungang Liu
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, PR China
| | - Wenyi Peng
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China
| | - Haotian Xu
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China
| | - Xiaofei Li
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China
| | - Xin Wang
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, PR China
| | - Shuilian Wu
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, PR China
| | - Gang Li
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China.
| | - Aruo Nan
- School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China; School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, PR China.
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Essola JM, Zhang M, Yang H, Li F, Xia B, Mavoungou JF, Hussain A, Huang Y. Exosome regulation of immune response mechanism: Pros and cons in immunotherapy. Bioact Mater 2024; 32:124-146. [PMID: 37927901 PMCID: PMC10622742 DOI: 10.1016/j.bioactmat.2023.09.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 09/06/2023] [Accepted: 09/25/2023] [Indexed: 11/07/2023] Open
Abstract
Due to its multiple features, including the ability to orchestrate remote communication between different tissues, the exosomes are the extracellular vesicles arousing the highest interest in the scientific community. Their size, established as an average of 30-150 nm, allows them to be easily uptaken by most cells. According to the type of cells-derived exosomes, they may carry specific biomolecular cargoes used to reprogram the cells they are interacting with. In certain circumstances, exosomes stimulate the immune response by facilitating or amplifying the release of foreign antigens-killing cells, inflammatory factors, or antibodies (immune activation). Meanwhile, in other cases, they are efficiently used by malignant elements such as cancer cells to mislead the immune recognition mechanism, carrying and transferring their cancerous cargoes to distant healthy cells, thus contributing to antigenic invasion (immune suppression). Exosome dichotomic patterns upon immune system regulation present broad advantages in immunotherapy. Its perfect comprehension, from its early biogenesis to its specific interaction with recipient cells, will promote a significant enhancement of immunotherapy employing molecular biology, nanomedicine, and nanotechnology.
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Affiliation(s)
- Julien Milon Essola
- School of Life Science, Advanced Research Institute of Multidisciplinary Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, No. 11, First North Road, Zhongguancun, Beijing, 100190, PR China
- University of Chinese Academy of Sciences. Beijing 100049, PR China
| | - Mengjie Zhang
- School of Life Science, Advanced Research Institute of Multidisciplinary Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China
| | - Haiyin Yang
- School of Life Science, Advanced Research Institute of Multidisciplinary Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China
| | - Fangzhou Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, No. 11, First North Road, Zhongguancun, Beijing, 100190, PR China
| | - Bozhang Xia
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, No. 11, First North Road, Zhongguancun, Beijing, 100190, PR China
- University of Chinese Academy of Sciences. Beijing 100049, PR China
| | - Jacques François Mavoungou
- Université Internationale de Libreville, Libreville, 20411, Gabon
- Central and West African Virus Epidemiology, Libreville, 2263, Gabon
- Département de phytotechnologies, Institut National Supérieur d’Agronomie et de Biotechnologie, Université des Sciences et Techniques de Masuku, Franceville, 901, Gabon
- Institut de Recherches Agronomiques et Forestiers, Centre National de la Recherche Scientifique et du développement Technologique, Libreville, 16182, Gabon
| | - Abid Hussain
- School of Life Science, Advanced Research Institute of Multidisciplinary Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China
| | - Yuanyu Huang
- School of Life Science, Advanced Research Institute of Multidisciplinary Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing, 100081, China
- Rigerna Therapeutics Co. Ltd., China
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Wang T, Li F, Lu Z. Ultra-conserved RNA: a novel biological tool with diagnostic and therapeutic potential. Discov Oncol 2023; 14:41. [PMID: 37036543 PMCID: PMC10086085 DOI: 10.1007/s12672-023-00650-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 04/03/2023] [Indexed: 04/11/2023] Open
Abstract
Ultra-conserved RNA (ucRNA) is a subset of long non-coding RNA, that is highly conserved among mice, rats and humans. UcRNA has attracted extensive attention in recent years for its potential biological significance in normal physiological function and diseases. However, due to the instability of RNA and the technical limitation, the function and mechanism of ucRNAs are largely unknown. Over the last two decades, researchers have made a lot of efforts to try to lift the veil of ucRNA in nervous, cardiovascular system and other systems as well as cancers. Since the concept of the glymphatic system is relatively new, we summarized here recent findings on the functions, regulation and the underlying mechanisms of ucRNAs in physiology and pathology. Meanwhile, pathology in some diseases is likely to contribute to abnormal expression of ucRNA in turn. We also discuss the technical challenges and bright prospects for future applications of ucRNAs in the diagnosis and treatment of diseases.
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Affiliation(s)
- Tingye Wang
- Department of Basic Medicine and Medical Technology, Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Feng Li
- Department of Basic Medicine and Medical Technology, Medical College, Yangzhou University, Yangzhou, Jiangsu, China
- Jiangsu Key Laboratory of Experimental & Translational Non-Coding RNA Research, Yangzhou, Jiangsu, China
| | - Zhanping Lu
- Department of Basic Medicine and Medical Technology, Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
- Jiangsu Key Laboratory of Experimental & Translational Non-Coding RNA Research, Yangzhou, Jiangsu, China.
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Khalafiyan A, Emadi-Baygi M, Wolfien M, Salehzadeh-Yazdi A, Nikpour P. Construction of a three-component regulatory network of transcribed ultraconserved regions for the identification of prognostic biomarkers in gastric cancer. J Cell Biochem 2023; 124:396-408. [PMID: 36748954 DOI: 10.1002/jcb.30373] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 01/04/2023] [Accepted: 01/09/2023] [Indexed: 02/08/2023]
Abstract
Altered expression and functional roles of the transcribed ultraconserved regions (T-UCRs), as genomic sequences with 100% conservation between the genomes of human, mouse, and rat, in the pathophysiology of neoplasms has already been investigated. Nevertheless, the relevance of the functions for T-UCRs in gastric cancer (GC) is still the subject of inquiry. In the current study, we first used a genome-wide profiling approach to analyze the expression of T-UCRs in GC patients. Then, we constructed a three-component regulatory network and investigated potential diagnostic and prognostic values of the T-UCRs. The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was used as a resource for the RNA-sequencing data. FeatureCounts was utilized to quantify the number of reads mapped to each T-UCR. Differential expression analysis was then conducted using DESeq2. In the following, interactions between T-UCRs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were combined into a three-component network. Enrichment analyses were performed and a protein-protein interaction (PPI) network was constructed. The R Survival package was utilized to identify survival-related significantly differentially expressed T-UCRs (DET-UCRs). Using an in-house cohort of GC tissues, expression of two DET-UCRs was furthermore experimentally verified. Our results showed that several T-UCRs were dysregulated in TCGA-STAD tumoral samples compared to nontumoral counterparts. The three-component network was constructed which composed of DET-UCRs, miRNAs, and mRNAs nodes. Functional enrichment and PPI network analyses revealed important enriched signaling pathways and gene ontologies such as "pathway in cancer" and regulation of cell proliferation and apoptosis. Five T-UCRs were significantly correlated with the overall survival of GC patients. While no expression of uc.232 was observed in our in-house cohort of GC tissues, uc.343 showed an increased expression, although not statistically significant, in gastric tumoral tissues. The constructed three-component regulatory network of T-UCRs in GC presents a comprehensive understanding of the underlying gene expression regulation processes involved in tumor development and can serve as a basis to investigate potential prognostic biomarkers and therapeutic targets.
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Affiliation(s)
- Anis Khalafiyan
- Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Modjtaba Emadi-Baygi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | - Markus Wolfien
- Department of System Biology and Bioinformatics, University of Rostock, Rostock, Germany
- Center for Medical Informatics, Dresden, Germany
| | - Ali Salehzadeh-Yazdi
- Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany
| | - Parvaneh Nikpour
- Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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de Oliveira JC. Transcribed Ultraconserved Regions: New regulators in cancer signaling and potential biomarkers. Genet Mol Biol 2023; 46:e20220125. [PMID: 36622962 PMCID: PMC9829027 DOI: 10.1590/1678-4685-gmb-2022-0125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 11/06/2022] [Indexed: 01/11/2023] Open
Abstract
The ultraconserved regions (UCRs) are 481 genomic elements, longer than 200 bp, 100% conserved in human, mouse, and rat genomes. Usually, coding regions are more conserved, but more than 80% of UCRs are either intergenic or intronic, and many of them produce long non-coding RNAs (lncRNAs). Recently, the deregulated expression of transcribed UCRs (T-UCRs) has been associated with pathological conditions. But, differently from many lncRNAs with recognized crucial effects on malignant cell processes, the role of T-UCRs in the control of cancer cell networks is understudied. Furthermore, the potential utility of these molecules as molecular markers is not clear. Based on this information, the present review aims to organize information about T-UCRs with either oncogenic or tumor suppressor role associated with cancer cell signaling, and better describe T-UCRs with potential utility as prognosis markers. Out of 481 T-UCRs, 297 present differential expression in cancer samples, 23 molecules are associated with tumorigenesis processes, and 12 have more clear potential utility as prognosis markers. In conclusion, T-UCRs are deregulated in several tumor types, highlighted as important molecules in cancer networks, and with potential utility as prognosis markers, although further investigation for translational medicine is still needed.
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Yu TX, Kalakonda S, Liu X, Han N, Chung HK, Xiao L, Rao JN, He TC, Raufman JP, Wang JY. Long noncoding RNA uc.230/CUG-binding protein 1 axis sustains intestinal epithelial homeostasis and response to tissue injury. JCI Insight 2022; 7:156612. [PMID: 36214222 PMCID: PMC9675575 DOI: 10.1172/jci.insight.156612] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 08/31/2022] [Indexed: 01/16/2023] Open
Abstract
Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.230 as a major regulator of epithelial renewal, apoptosis, and barrier function. Compared with controls, intestinal mucosal tissues from patients with ulcerative colitis and from mice with colitis or fasted for 48 hours had increased levels of uc.230. Silencing uc.230 inhibited the growth of intestinal epithelial cells (IECs) and organoids and caused epithelial barrier dysfunction. Silencing uc.230 also increased IEC vulnerability to apoptosis, whereas increasing uc.230 levels protected IECs against cell death. In mice with colitis, reduced uc.230 levels enhanced mucosal inflammatory injury and delayed recovery. Mechanistic studies revealed that uc.230 increased CUG-binding protein 1 (CUGBP1) by acting as a natural decoy RNA for miR-503, which interacts with Cugbp1 mRNA and represses its translation. These findings indicate that uc.230 sustains intestinal mucosal homeostasis by promoting epithelial renewal and barrier function and that it protects IECs against apoptosis by serving as a natural sponge for miR-503, thereby preserving CUGBP1 expression.
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Affiliation(s)
- Ting-Xi Yu
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Sudhakar Kalakonda
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Xiangzheng Liu
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Naomi Han
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Hee K. Chung
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Lan Xiao
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.,Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
| | - Jaladanki N. Rao
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.,Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
| | - Tong-Chuan He
- Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois, USA
| | - Jean-Pierre Raufman
- Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.,Department of Medicine and
| | - Jian-Ying Wang
- Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.,Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.,Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Gao SS, Zhang ZK, Wang XB, Ma Y, Yin GQ, Guo XB. Role of transcribed ultraconserved regions in gastric cancer and therapeutic perspectives. World J Gastroenterol 2022; 28:2900-2909. [PMID: 35978878 PMCID: PMC9280734 DOI: 10.3748/wjg.v28.i25.2900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/08/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is the fourth leading cause of cancer-related death. The occurrence and development of GC is a complex process involving multiple biological mechanisms. Although traditional regulation modulates molecular functions related to the occurrence and development of GC, the comprehensive mechanisms remain unclear. Ultraconserved region (UCR) refers to a genome sequence that is completely conserved in the homologous regions of the human, rat and mouse genomes, with 100% identity, without any insertions or deletions, and often located in fragile sites and tumour-related genes. The transcribed UCR (T-UCR) is transcribed from the UCR and is a new type of long noncoding RNA. Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC, revealing a new mechanism underlying GC. Therefore, this article aims to review the relevant research on T-UCRs in GC, as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC, to provide new strategies for GC diagnosis and treatment.
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Affiliation(s)
- Shen-Shuo Gao
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Zhi-Kai Zhang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Xu-Bin Wang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Yan Ma
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Guo-Qing Yin
- Department of Anus and Intestine Surgery, Qingzhou Hospital Affiliated to Shandong First Medical University, Qingzhou 262500, Shandong Province, China
| | - Xiao-Bo Guo
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
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Bozgeyik I. The dark matter of the human genome and its role in human cancers. Gene 2022; 811:146084. [PMID: 34843880 DOI: 10.1016/j.gene.2021.146084] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/06/2021] [Accepted: 11/23/2021] [Indexed: 12/26/2022]
Abstract
The transcribed ultra-conserved regions (T-UCRs) are a novel family of non-coding RNAs which are absolutely conserved (100%) across orthologous regions of the human, mouse, and rat genomes. T-UCRs represent a small portion of the human genome that is likely to be functional but does not code for proteins and is referred to as the "dark matter" of the human genome. Although T-UCRs are ubiquitously expressed, tissue- and disease-specific expression of T-UCRs have also been observed. Accumulating evidence suggests that T-UCRs are differentially expressed and involved in the malignant transformation of human tumors through various genetic and epigenetic regulatory mechanisms. Therefore, T-UCRs are novel candidate predisposing biomarkers for cancer development. T-UCRs have shown to drive malignant transformation of human cancers through regulating non-coding RNAs and/or protein coding genes. However, the functions and fate of most T-UCRs remain mysterious. Here, we review and highlight the current knowledge on these ultra-conserved elements in the formation and progression of human cancers.
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Affiliation(s)
- Ibrahim Bozgeyik
- Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey.
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New insights into exosome mediated tumor-immune escape: Clinical perspectives and therapeutic strategies. Biochim Biophys Acta Rev Cancer 2021; 1876:188624. [PMID: 34487817 DOI: 10.1016/j.bbcan.2021.188624] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 08/30/2021] [Accepted: 09/01/2021] [Indexed: 12/13/2022]
Abstract
Recent advances in extracellular vesicle biology have uncovered a substantial role in maintaining cell homeostasis in health and disease conditions by mediating intercellular communication, thus catching the scientific community's attention worldwide. Extracellular microvesicles, some called exosomes, functionally transfer biomolecules such as proteins and non-coding RNAs from one cell to another, influencing the local environment's biology. Although numerous advancements have been made in treating cancer patients with immune therapy, controlling the disease remains a challenge in the clinic due to tumor-driven interference with the immune response and inability of immune cells to clear cancer cells from the body. The present review article discusses the recent findings and knowledge gaps related to the role of exosomes derived from tumors and the tumor microenvironment cells in tumor escape from immunosurveillance. Further, we highlight examples where exosomal non-coding RNAs influence immune cells' response within the tumor microenvironment and favor tumor growth and progression. Therefore, exosomes can be used as a therapeutic target for the treatment of human cancers.
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Ashrafizadeh M, Zarrabi A, Hashemi F, Moghadam ER, Hashemi F, Entezari M, Hushmandi K, Mohammadinejad R, Najafi M. Curcumin in cancer therapy: A novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects. Life Sci 2020; 256:117984. [PMID: 32593707 DOI: 10.1016/j.lfs.2020.117984] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 06/14/2020] [Accepted: 06/15/2020] [Indexed: 12/15/2022]
Abstract
Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal candidate in overcoming and eradication of cancer. To date, various chemotherapeutic agents have been applied in cancer therapy and paclitaxel (PTX) is one of them. PTX is a key member of taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia, and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. Besides, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, cardiotoxicity and so on, demanding novel strategies in obviating PTX issues. Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, anti-oxidant, anti-inflammatory, anti-diabetic and so on. In the current review, we demonstrate that curcumin, a naturally occurring nutraceutical compound is able to enhance anti-tumor activity of PTX against different cancers. Besides, curcumin administration reduces adverse effects of PTX due to its excellent pharmacological activities. These topics are discussed with an emphasis on molecular pathways to provide direction for further studies in revealing other signaling networks.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla 34956, Istanbul, Turkey; Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzia, Istanbul 34956, Turkey
| | - Farid Hashemi
- DVM, Graduated, Young Researcher and Elite Club, Kazerun Branch, Islamic Azad University, Kazeroon, Iran
| | - Ebrahim Rahmani Moghadam
- Department of Anatomical Sciences, School of Medicine, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fardin Hashemi
- Student Research Committee, Department of Physiotherapy, Faculty of Rehabilitation, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Reza Mohammadinejad
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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