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Li D, Chu X, Liu W, Ma Y, Tian X, Yang Y. The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies. RNA Biol 2025; 22:1-14. [PMID: 39718205 DOI: 10.1080/15476286.2024.2440683] [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] [Revised: 11/03/2024] [Accepted: 12/04/2024] [Indexed: 12/25/2024] Open
Abstract
The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (m6A). Aberrant regulation of RBPs, such as HuR and YBX1, typically enhances tumour immune escape and impacts prognosis of GI tumour patients. Further, while targeting RBPs offers a promising strategy for improving immunotherapy in GI cancers, the mechanisms by which RBPs regulate the TIME in these tumours remain poorly understood, and the therapeutic application is still in its early stages. This review summarizes current advances in exploring the roles of RBPs in regulating genes expression and their effect on the TIME of GI tumours, then providing theoretical insights for RBP-targeted cancer therapies.
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Affiliation(s)
- Dongqi Li
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
| | - Xiangyu Chu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Weikang Liu
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
| | - Yongsu Ma
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
| | - Xiaodong Tian
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
| | - Yinmo Yang
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
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Moghaddasnejad MR, Keshavarz A, Mardi A, Sherafat NS, Aghebati-Maleki L, Mohammadi MH. LncRNAs as behind-the-scenes molecules in cancer progression through regulating tumor-associated innate immune system cells. Mol Biol Rep 2025; 52:449. [PMID: 40338353 DOI: 10.1007/s11033-025-10513-3] [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: 02/12/2025] [Accepted: 04/14/2025] [Indexed: 05/09/2025]
Abstract
Long non-coding RNAs (lncRNAs) have emerged as critical regulators in cancer biology, particularly in the modulation of innate immune cells within the tumor microenvironment. These lncRNAs significantly influence the phenotype and function of immune cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), natural killer cells (NK), neutrophils, and γδT cells. Thus, lncRNAs emerge as pivotal molecules in cancer development due to their capacity to modulate the innate immune system. Understanding the intricate mechanisms by which lncRNAs influence tumor-associated immune cells can pave the way for novel therapeutic strategies to restore effective anti-tumor immunity. This review highlights the diverse roles of lncRNAs in regulating the differentiation, activation, and effector functions of innate immune cells within the complex tumor microenvironment.
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Affiliation(s)
| | - Ali Keshavarz
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, P.O.Box: 15468-15514, Tehran, Iran
| | - Amirhossein Mardi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran
| | - Negar Sadat Sherafat
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Mohammad Hossein Mohammadi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, P.O.Box: 15468-15514, Tehran, Iran.
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3
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Song Z, Suo C, Liu Y, Jin L, Xie X, Liu J, Yu B, Wang Y, Zhang Z, Xie D. Comprehensive evaluation of non-coding RNA-mediated autophagy regulation in myocardial ischemia-reperfusion injury. Front Pharmacol 2025; 16:1581341. [PMID: 40351430 PMCID: PMC12062134 DOI: 10.3389/fphar.2025.1581341] [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: 02/22/2025] [Accepted: 04/11/2025] [Indexed: 05/14/2025] Open
Abstract
Ischemic heart disease remains a major global health challenge, with myocardial ischemia-reperfusion injury (MIRI) being one of its most common and severe pathophysiological complications. The pathogenesis of MIRI is multifaceted, involving oxidative stress, inflammatory responses, apoptotic pathways, and autophagic regulation. Notably, autophagy exerts a dual regulatory effect, where maintaining optimal autophagic flux is essential for cardiac homeostasis. Emerging evidence underscores the crucial role of non-coding RNAs (ncRNAs) in modulating these pathological processes. In particular, long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) have been identified as key regulators of autophagy-mediated MIRI progression through complex molecular networks. This review provides a systematic analysis of the molecular pathways through which ncRNAs influence MIRI pathogenesis, with a specific focus on their autophagy-regulatory mechanisms. These insights may enhance our understanding of MIRI pathobiology and facilitate the development of novel therapeutic strategies.
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Affiliation(s)
- Zhongyang Song
- Department of Oncology, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, China
- Gansu Institute of Cardiovascular Diseases, Lanzhou, Gansu, China
| | - Chang Suo
- School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China
| | - Yongqi Liu
- Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, China
| | - Ling Jin
- Longyao Industry Innovation Institute, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, China
| | - Xiaodong Xie
- Institute of Genetics, School of Basic Medicine, Lanzhou University, Lanzhou, China
| | - Jian Liu
- Department of Critical Care Medicine, Maternal and Child Healthcare Hospital of Gansu Province, Lanzhou, China
| | - Bo Yu
- Department of General Surgery, The Second People’s Hospital of Lanzhou City, Lanzhou, China
| | - Yanzhen Wang
- Gansu Institute of Cardiovascular Diseases, Lanzhou, Gansu, China
| | - Zhiming Zhang
- Department of Oncology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, China
| | - Dingxiong Xie
- Gansu Institute of Cardiovascular Diseases, Lanzhou, Gansu, China
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4
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Wang Y, Wang S, He H, Bai Y, Liu Z, Sabihi SS. Mechanisms of apoptosis-related non-coding RNAs in ovarian cancer: a narrative review. Apoptosis 2025; 30:553-578. [PMID: 39833637 DOI: 10.1007/s10495-024-02074-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] [Accepted: 12/27/2024] [Indexed: 01/22/2025]
Abstract
Ovarian cancer remains a major challenge in oncology due to its complex biology and late-stage diagnosis. Recent advances in molecular biology have highlighted the crucial role of non-coding RNAs (ncRNAs) in regulating apoptosis and cancer progression. NcRNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have emerged as significant players in the molecular networks governing ovarian cancer. Despite these insights, the precise mechanisms by which ncRNAs influence ovarian cancer pathology are not fully understood. This complexity, combined with the heterogeneity of the disease and the development of treatment resistance, poses substantial obstacles to effective therapeutic development. Additionally, the lack of reliable early detection methods further complicates treatment strategies. This manuscript reviews the current state of research on ncRNAs in ovarian cancer, discusses the challenges in translating these findings into clinical applications, and outlines potential future directions. Emphasis is placed on the need for integrated approaches to unravel the intricate roles of ncRNAs, improve early detection, and develop personalized treatment strategies to address the diverse and evolving nature of ovarian cancer. While these findings provide valuable insights, it is crucial to recognize that many results are based on preclinical studies and require further validation to establish their clinical applicability.
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Affiliation(s)
- Yue Wang
- Department of Obstetrics and Gynecology, Tang Du Hospital, The Air Force Military Medical University, Xi'an, 710038, China
| | - Shirui Wang
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710038, China
| | - Haiyan He
- Department of Obstetrics and Gynecology, Tang Du Hospital, The Air Force Military Medical University, Xi'an, 710038, China
| | - Yingying Bai
- Department of Obstetrics and Gynecology, Tang Du Hospital, The Air Force Military Medical University, Xi'an, 710038, China
| | - Zhuo Liu
- Department of Obstetrics and Gynecology, Xi'an International Medical Center Hospital, Xi'an, 710038, China
| | - Sima-Sadat Sabihi
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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Ju Y, Lv Y, Liu X, Lu J, Shi Y, Guo H, Xu S, Tian J, Yang J, Zhong J. Role of long non-coding RNAs in the regulation of ferroptosis in tumors. Front Immunol 2025; 16:1568567. [PMID: 40191204 PMCID: PMC11968707 DOI: 10.3389/fimmu.2025.1568567] [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: 01/30/2025] [Accepted: 03/06/2025] [Indexed: 04/09/2025] Open
Abstract
Normal cells begin to grow indefinitely and immortalize to form tumor cells after an external stimulus resulting in a genetic mutation. Effective killing of tumor cells is the basis of various cancer therapies. Ferroptosis is a class of cell death types dependent on iron and cellular lipid peroxidation. Tumors themselves are iron-dependent, and conventional radiotherapy also sensitizes cancer cells to ferroptosis. Increasing the sensitivity of tumor cells to ferroptosis may be a potential therapeutic strategy to overcome the resistance mechanisms of conventional cancer therapy. Long noncoding RNAs (LncRNAs) are a class of transcripts more than 200 nucleotides in length that regulate gene expression at multiple levels and are involved in biological processes such as cell differentiation, cell cycle arrest, and maintenance of tumor stemness. Recent studies have found that lncRNAs regulate ferroptosis of tumor cells through multiple mechanisms and may influence or ameliorate tumor resistance to chemotherapeutic agents. With the continuous maturation of nanomaterials technology, it may provide new means for cancer treatment by regulating the levels of ferroptosis-related lncRNAs inside tumors as well as increasing the levels of Fe2+ and ROS inside tumors. In this paper, we systematically introduce the regulatory mechanism of lncRNAs in ferroptosis, the role of ferroptosis in tumor immunotherapy and the application of lncRNAs combined with ferroptosis in nanomaterials, which provides new perspectives for tumor therapy.
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Affiliation(s)
- Ying Ju
- Department of Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Yuanhao Lv
- Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Xu Liu
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Jing Lu
- Department of Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Yashen Shi
- Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Huimin Guo
- Department of Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Siguang Xu
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Jiaqi Tian
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Jun Yang
- Department of Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Jiateng Zhong
- Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
- Xinxiang Engineering Technology Research Center of Digestive Tumor Molecular Diagnosis, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
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Wang Y, Yuan J, Guo K, Zhang Z, Zhu J, Arya S, Huang G, Li S, Chen Q, Liu X, Jia J. Identification and functional characterization of T-cell exhaustion-associated lncRNA AL031775.1 in osteosarcoma: a novel therapeutic target. Front Immunol 2025; 16:1517971. [PMID: 40066455 PMCID: PMC11891247 DOI: 10.3389/fimmu.2025.1517971] [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: 10/27/2024] [Accepted: 02/04/2025] [Indexed: 05/13/2025] Open
Abstract
Background Osteosarcoma, an aggressive bone malignancy predominantly affecting children and adolescents, presents significant therapeutic challenges with a 5-year survival rate below 30% in metastatic cases. T-cell exhaustion, characterized by the overexpression of immune checkpoint molecules, contributes to osteosarcoma progression and immune evasion. Although targeting these inhibitory pathways has shown potential in restoring T-cell activity, the molecular regulators of T-cell depletion in osteosarcoma are poorly understood. Methods This study employed comprehensive bioinformatics analyses on osteosarcoma samples from the TARGET database, combined with normal tissue data from the GTEx database, to identify T-cell exhaustion-associated genes and their co-expressed long non-coding RNAs (lncRNAs). Gene ontology and KEGG pathway analyses were used to elucidate immune-related pathway enrichments. A six-lncRNA prognostic model was established using LASSO regression and validated in separate cohorts. Functional assays evaluated the impact of the lncRNA AL031775.1 on osteosarcoma cell behavior and T-cell function. Results Twenty-four key T-cell exhaustion-related genes were identified and significantly enriched in immune-related pathways, indicating their importance in the osteosarcoma immune microenvironment. The constructed six-lncRNA model stratified patients by survival prognosis, showing robust predictive performance across cohorts. Among the six identified lncRNAs, AL031775.1 is notably downregulated in osteosarcoma patients and significantly promotes osteosarcoma cell proliferation, migration, and invasion while contributing to T-cell exhaustion. In T cells, downregulation of AL031775.1 impairs antitumor immunity, upregulates immune checkpoint molecules LAG3, PD1, and CTLA4, and diminishes T-cell cytotoxic activity against tumor cells. Conclusion This study identifies a novel six-lncRNA prognostic model and highlights the therapeutic potential of AL031775.1 in managing osteosarcoma by enhancing T-cell immunity and counteracting tumor progression. Targeting AL031775.1 represents a promising approach to improve immunotherapy efficacy in osteosarcoma. These findings provide critical insights into the molecular regulation of T-cell exhaustion and suggest a new avenue for therapeutic intervention.
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Affiliation(s)
- Yameng Wang
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, Jiangxi, China
- Department of Orthopedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jinghong Yuan
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, Jiangxi, China
| | - Keying Guo
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, Jiangxi, China
| | - Zhuoer Zhang
- Department of Bone and Soft Tissue Tumors, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China
| | - Junchao Zhu
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, Jiangxi, China
| | - Shahrzad Arya
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Guowen Huang
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, Jiangxi, China
| | - Shengqin Li
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, Jiangxi, China
| | - Qi Chen
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xijuan Liu
- Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jingyu Jia
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- The Second Affiliated Hospital of Nanchang University, Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, Jiangxi, China
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7
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McDonald JF. Adaptive Significance of Non-coding RNAs: Insights from Cancer Biology. Mol Biol Evol 2025; 42:msae269. [PMID: 39761690 PMCID: PMC11725524 DOI: 10.1093/molbev/msae269] [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: 09/20/2024] [Revised: 11/20/2024] [Accepted: 12/18/2024] [Indexed: 01/15/2025] Open
Abstract
The molecular basis of adaptive evolution and cancer progression are both complex processes that share many striking similarities. The potential adaptive significance of environmentally-induced epigenetic changes is currently an area of great interest in both evolutionary and cancer biology. In the field of cancer biology intense effort has been focused on the contribution of stress-induced non-coding RNAs (ncRNAs) in the activation of epigenetic changes associated with elevated mutation rates and the acquisition of environmentally adaptive traits. Examples of this process are presented and combined with more recent findings demonstrating that stress-induced ncRNAs are transferable from somatic to germline cells leading to cross-generational inheritance of acquired adaptive traits. The fact that ncRNAs have been implicated in the transient adaptive response of various plants and animals to environmental stress is consistent with findings in cancer biology. Based on these collective observations, a general model as well as specific and testable hypotheses are proposed on how transient ncRNA-mediated adaptive responses may facilitate the transition to long-term biological adaptation in both cancer and evolution.
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Affiliation(s)
- John F McDonald
- Professor Emeritus, School of Biological Sciences, Integrated Cancer Research Center, Georgia Institute of Technology, Atlanta, GA, USA
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Mirzaei S, Ahangari F, Faramarzi F, Khoshnazar SM, Khormizi FZ, Aghagolzadeh M, Rostami M, Asghariazar V, Alimohammadi M, Rahimzadeh P, Farahani N. MicroRNA-146 family: Molecular insights into their role in regulation of signaling pathways in glioma progression. Pathol Res Pract 2024; 264:155707. [PMID: 39536541 DOI: 10.1016/j.prp.2024.155707] [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: 08/22/2024] [Revised: 11/05/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
Glioma is a highly lethal brain cancer in humans. Despite advancements in treatment, the prognosis for patients remains unfavorable. Epigenetic factors, along with their interactions and non-coding RNAs (ncRNAs), are crucial in glioma cells' development and aggressive characteristics. MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) that modulate the expression of various genes by binding to target mRNA molecules. They play a critical role in regulating essential biological mechanisms such as cell proliferation and differentiation, cell cycle, and apoptosis. MiR-146a/miR-146b is a significant and prevalent miRNA whose expression alterations are linked to various pathological changes in cancer cells, as well as the modulation of several cellular signaling pathways, including NF-κB, TGF-β, PI3K/Akt, and Notch-1. Scientists may identify novel targets in clinical settings by studying the complicated link between Mir-146a/mir-146b, drug resistance, molecular pathways, and pharmacological intervention in gliomas. Additionally, its interactions with other ncRNAs, such as circular RNA and long non-coding RNA, contribute to the pathogenesis of glioma. As well as miR-146 holds potential as both a diagnostic and therapeutic biomarker for patients with this condition. In the current review, we investigate the significance of miRNAs in the context of glioma, with a particular focus on the critical role of Mir-146a/mir-146b in glioma tumors. Additionally, we examined the clinical relevance of this miRNA, highlighting its potential implications for diagnosis and treatment.
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Affiliation(s)
- Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Fatemeh Ahangari
- Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
| | - Fatemeh Faramarzi
- Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Seyedeh Mahdieh Khoshnazar
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Mahboobeh Aghagolzadeh
- Department of Biology, Faculty of Basic Sciences, University of Shahid Chamran of Ahvaz, Ahvaz, Iran
| | - Mohammadreza Rostami
- Division of Food Safety and Hygiene, Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Food Science and Nutrition Group (FSAN), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Vahid Asghariazar
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Payman Rahimzadeh
- Surgical Research Society (SRS), Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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Arshi A, Mahmoudi E, Raeisi F, Dehghan Tezerjani M, Bahramian E, Ahmed Y, Peng C. Exploring potential roles of long non-coding RNAs in cancer immunotherapy: a comprehensive review. Front Immunol 2024; 15:1446937. [PMID: 39257589 PMCID: PMC11384988 DOI: 10.3389/fimmu.2024.1446937] [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: 06/10/2024] [Accepted: 08/05/2024] [Indexed: 09/12/2024] Open
Abstract
Cancer treatment has long been fraught with challenges, including drug resistance, metastasis, and recurrence, making it one of the most difficult diseases to treat effectively. Traditional therapeutic approaches often fall short due to their inability to target cancer stem cells and the complex genetic and epigenetic landscape of tumors. In recent years, cancer immunotherapy has revolutionized the field, offering new hope and viable alternatives to conventional treatments. A particularly promising area of research focuses on non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), and their role in cancer resistance and the modulation of signaling pathways. To address these challenges, we performed a comprehensive review of recent studies on lncRNAs and their impact on cancer immunotherapy. Our review highlights the crucial roles that lncRNAs play in affecting both innate and adaptive immunity, thereby influencing the outcomes of cancer treatments. Key observations from our review indicate that lncRNAs can modify the tumor immune microenvironment, enhance immune cell infiltration, and regulate cytokine production, all of which contribute to tumor growth and resistance to therapies. These insights suggest that lncRNAs could serve as potential targets for precision medicine, opening up new avenues for developing more effective cancer immunotherapies. By compiling recent research on lncRNAs across various cancers, this review aims to shed light on their mechanisms within the tumor immune microenvironment.
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Affiliation(s)
- Asghar Arshi
- Department of Biology, York University, Toronto, ON, Canada
| | - Esmaeil Mahmoudi
- Young Researchers and Elite Club, Islamic Azad University, Shahrekord, Iran
| | | | - Masoud Dehghan Tezerjani
- Department of bioinformatics, School of Advanced Medical Technologies, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elham Bahramian
- Department of Biological Sciences, University of Arkansas, Fayetteville, AR, United States
| | - Yeasin Ahmed
- Department of Biological Sciences, University of Arkansas, Fayetteville, AR, United States
| | - Chun Peng
- Department of Biology, York University, Toronto, ON, Canada
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10
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Zhang Y, Zhan L, Jiang X, Tang X. Comprehensive review for non-coding RNAs: From mechanisms to therapeutic applications. Biochem Pharmacol 2024; 224:116218. [PMID: 38643906 DOI: 10.1016/j.bcp.2024.116218] [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: 02/01/2024] [Revised: 04/14/2024] [Accepted: 04/16/2024] [Indexed: 04/23/2024]
Abstract
Non-coding RNAs (ncRNAs) are an assorted collection of transcripts that are not translated into proteins. Since their discovery, ncRNAs have gained prominence as crucial regulators of various biological functions across diverse cell types and tissues, and their abnormal functioning has been implicated in disease. Notably, extensive research has focused on the relationship between microRNAs (miRNAs) and human cancers, although other types of ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as significant contributors to human disease. In this review, we provide a comprehensive summary of our current knowledge regarding the roles of miRNAs, lncRNAs, and circRNAs in cancer and other major human diseases, particularly cancer, cardiovascular, neurological, and infectious diseases. Moreover, we discuss the potential utilization of ncRNAs as disease biomarkers and as targets for therapeutic interventions.
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Affiliation(s)
- YanJun Zhang
- College of Pharmacy and Traditional Chinese Medicine, Jiangsu College of Nursing, Huaian, Jiangsu, 223005, China
| | - Lijuan Zhan
- College of Pharmacy and Traditional Chinese Medicine, Jiangsu College of Nursing, Huaian, Jiangsu, 223005, China
| | - Xue Jiang
- College of Pharmacy and Traditional Chinese Medicine, Jiangsu College of Nursing, Huaian, Jiangsu, 223005, China.
| | - Xiaozhu Tang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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11
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Li X, Meng Y, Gu B. A novel immune‑related lncRNA as a prognostic biomarker in HER2 + breast cancer. Oncol Lett 2024; 27:269. [PMID: 38686356 PMCID: PMC11057035 DOI: 10.3892/ol.2024.14402] [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: 12/04/2023] [Accepted: 03/15/2024] [Indexed: 05/02/2024] Open
Abstract
Human epidermal growth factor receptor 2 (HER2)+ breast cancer is characterized by high malignancy and poor prognosis. Long non-coding (lnc)RNAs are crucial in breast cancer progression and prognosis, especially in tumor-associated immune processes. The present study aimed to elucidate novel lncRNAs related to immune function that could serve as biomarkers for both diagnosis and prognosis of this cancer subtype. Using data from The Cancer Genome Atlas and The Immunology Database and Analysis Portal, correlation analysis was performed to identify differentially expressed lncRNAs and immune-related genes. Through receiver operating characteristic analysis, the diagnostic value of specific lncRNAs was identified and evaluated, with a focus on their capacity to distinguish between cancerous and non-cancerous states. The present research revealed 22 differentially expressed lncRNAs and 23 differentially expressed immune-related genes, with 19 immune-related lncRNAs. A total of 13 of these lncRNAs demonstrated diagnostic relevance. In particular, it was demonstrated that the expression of lncRNA CTC-537E7.2 was significantly correlated with patient survival, suggesting its potential as a prognostic marker. Additionally, the expression of lncRNA CTC-537E7.2 was significantly correlated with clinical parameters, such as hormone receptor status and patient demographics. Moreover, it exhibited associations with four distinct immune cell types and demonstrated involvement in the Janus kinase-signal transducer and activator of transcription pathway. Further assessment by in situ hybridization confirmed the increased expression of lncRNA CTC-537E7.2 in samples from HER2+ patients, reinforcing its significance. In summary, the present study uncovered a novel prognostic biomarker for HER2+ breast cancer, thereby laying the groundwork for investigating the underlying molecular mechanisms driving the development of this subtype of breast cancer.
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Affiliation(s)
- Xinwei Li
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China
- Department of Clinical Laboratory, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China
| | - Yue Meng
- Department of Clinical Laboratory, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China
| | - Bing Gu
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China
- Department of Clinical Laboratory, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China
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12
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Guo Y, Jia X, Du P, Wang J, Du Y, Li B, Xue Y, Jiang J, Cai Y, Yang Q. Mechanistic insights into the ameliorative effects of Xianglianhuazhuo formula on chronic atrophic gastritis through ferroptosis mediated by YY1/miR-320a/TFRC signal pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 323:117608. [PMID: 38158098 DOI: 10.1016/j.jep.2023.117608] [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: 10/10/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Xianglianhuazhuo formula (XLHZ) has a potential therapeutic effect on chronic atrophic gastritis (CAG). However, the specific molecular mechanism remains unclear. AIM OF THE STUDY To evaluate the effect of XLHZ on CAG in vitro and in vivo and its potential mechanisms. METHODS A rat model of CAG was established using a composite modeling method, and the pathological changes and ultrastructure of gastric mucosa were observed. YY1/miR-320a/TFRC and ferroptosis-related molecules were detected. An MNNG-induced gastric epithelial cell model was established in vitro to evaluate the inhibitory effect of XLHZ on cell ferroptosis by observing cell proliferation, migration, invasion, apoptosis, and molecules related to ferroptosis. The specific mechanism of action of XLHZ in treating CAG was elucidated by silencing or overexpression of targets. RESULTS In vivo experiments showed that XLHZ could improve the pathological status and ultrastructure of gastric mucosa and inhibit ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway. The results in vitro demonstrated that transfection of miR-320a mimics inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. MiR-320a targeted TFRC and inhibited ferroptosis. Overexpression of TFRC reversed the inhibitory effect of miR-320a overexpression on cell proliferation. The effect of XLHZ was consistent with that of miR-320a. YY1 targeted miR-320a, and its overexpression promoted ferroptosis. CONCLUSION XLHZ inhibited ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway, ultimately impeding the progression of CAG.
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Affiliation(s)
- Yuxi Guo
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Xuemei Jia
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Pengli Du
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Jie Wang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Yao Du
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Bolin Li
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Yucong Xue
- College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050200, China
| | - Jianming Jiang
- College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050200, China
| | - Yanru Cai
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China.
| | - Qian Yang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China.
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Dong C, Hui P, Wu Z, Li J, Man X. CircRNA LOC729852 promotes bladder cancer progression by regulating macrophage polarization and recruitment via the miR-769-5p/IL-10 axis. J Cell Mol Med 2024; 28:e18225. [PMID: 38506082 PMCID: PMC10951884 DOI: 10.1111/jcmm.18225] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 02/19/2024] [Accepted: 02/23/2024] [Indexed: 03/21/2024] Open
Abstract
Circular RNAs (circRNAs) function as tumour promoters or suppressors in bladder cancer (BLCA) by regulating genes involved in macrophage recruitment and polarization. However, the underlying mechanisms are largely unknown. The aim of this study was to determine the biological role of circLOC729852 in BLCA. CircLOC729852 was upregulated in BLCA tissues and correlated with increased proliferation, migration and epithelial mesenchymal transition (EMT) of BCLA cells. MiR-769-5p was identified as a target for circLOC729852, which can upregulate IL-10 expression by directly binding to and suppressing miR-769-5p. Furthermore, our results indicated that the circLOC729852/miR-769-5p/IL-10 axis modulates autophagy signalling in BLCA cells and promotes the recruitment and M2 polarization of TAMs by activating the JAK2/STAT3 signalling pathway. In addition, circLOC729852 also promoted the growth of BLCA xenografts and M2 macrophage infiltration in vivo. Thus, circLOC729852 functions as an oncogene in BLCA by inducing secretion of IL-10 by the M2 TAMs, which then facilitates tumour cell growth and migration. Taken together, circLOC729852 is a potential diagnostic biomarker and therapeutic target for BLCA.
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Affiliation(s)
- Changming Dong
- Department of Urology, China Medical UniversityThe First Hospital of China Medical UniversityShenyangLiaoningChina
- Department of UrologyThe First Hospital of China Medical UniversityShenyangLiaoningPR China
| | - Pengyu Hui
- Department of UrologyThe Second Affiliated Hospital of Xi'an Medical UniversityXi'anShaanxiChina
| | - Zhengqi Wu
- Department of Urology, China Medical UniversityThe First Hospital of China Medical UniversityShenyangLiaoningChina
| | - Jianfeng Li
- Department of Urology, China Medical UniversityThe First Hospital of China Medical UniversityShenyangLiaoningChina
| | - Xiaojun Man
- Department of Urology, China Medical UniversityThe First Hospital of China Medical UniversityShenyangLiaoningChina
- Department of UrologyThe First Hospital of China Medical UniversityShenyangLiaoningPR China
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14
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Hussain MS, Shaikh NK, Agrawal M, Tufail M, Bisht AS, Khurana N, Kumar R. Osteomyelitis and non-coding RNAS: A new dimension in disease understanding. Pathol Res Pract 2024; 255:155186. [PMID: 38350169 DOI: 10.1016/j.prp.2024.155186] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/27/2024] [Accepted: 01/31/2024] [Indexed: 02/15/2024]
Abstract
Osteomyelitis, a debilitating bone infection, presents considerable clinical challenges due to its intricate etiology and limited treatment options. Despite strides in surgical and chemotherapeutic interventions, the treatment landscape for osteomyelitis remains unsatisfactory. Recent attention has focused on the role of non-coding RNAs (ncRNAs) in the pathogenesis and progression of osteomyelitis. This review consolidates current knowledge on the involvement of distinct classes of ncRNAs, including microRNAs, long ncRNAs, and circular RNAs, in the context of osteomyelitis. Emerging evidence from various studies underscores the potential of ncRNAs in orchestrating gene expression and influencing the differentiation of osteoblasts and osteoclasts, pivotal processes in bone formation. The review initiates by elucidating the regulatory functions of ncRNAs in fundamental cellular processes such as inflammation, immune response, and bone remodeling, pivotal in osteomyelitis pathology. It delves into the intricate network of interactions between ncRNAs and their target genes, illuminating how dysregulation contributes to the establishment and persistence of osteomyelitic infections. Understanding their regulatory roles may pave the way for targeted diagnostic tools and innovative therapeutic interventions, promising a paradigm shift in the clinical approach to this challenging condition. Additionally, we delve into the promising therapeutic applications of these molecules, envisioning novel diagnostic and treatment approaches to enhance the management of this challenging bone infection.
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Affiliation(s)
- Md Sadique Hussain
- Department of Pharmacology, School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan 302017, India
| | - Nusrat K Shaikh
- Department of Quality Assurance, Smt. N. M. Padalia Pharmacy College, Ahmedabad, 382210 Gujarat, India
| | - Mohit Agrawal
- Department of Pharmacology, School of Medical & Allied Sciences, K.R. Mangalam University, Gurugram 122103, India
| | - Muhammad Tufail
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China.
| | - Ajay Singh Bisht
- School of Pharmaceutical Sciences, Shri Guru Ram Rai University, Patel Nagar, Dehradun, Uttarakhand 248001, India
| | - Navneet Khurana
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Rajesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
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15
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Alharbi KS. The ncRNA-TGF-β axis: Unveiling new frontiers in colorectal cancer research. Pathol Res Pract 2024; 254:155138. [PMID: 38266458 DOI: 10.1016/j.prp.2024.155138] [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: 11/05/2023] [Revised: 01/07/2024] [Accepted: 01/11/2024] [Indexed: 01/26/2024]
Abstract
Colorectal cancer (CRC) poses a substantial global challenge, necessitating a deeper understanding of the molecular underpinnings governing its onset and progression. The transforming growth factor beta (TGF-β) network has been a well-recognized cornerstone in advancing CRC. Nevertheless, a recent study has highlighted the growing importance of non-coding RNAs (ncRNAs) in this context. This comprehensive review aims to present an extensive examination of the interaction between ncRNAs and TGF-signaling. Noncoding RNAs (ncRNAs), encompassing circular RNAs (circRNAs), long-ncRNAs (lncRNAs), and microRNAs (miRNAs), have surfaced as pivotal modulators governing various aspects of TGF-β signaling. MiRNAs have been discovered to target elements within the TGF-β signaling, either enhancing or inhibiting signaling, depending on the context. LncRNAs have been associated with CRC progression, functioning as miRNA sponges or directly influencing TGF-β pathway elements. Even circRNAs, a relatively recent addition to the ncRNA family, have impacted CRC, affecting TGF-β signaling through diverse mechanisms. This review encompasses recent progress in comprehending specific ncRNAs involved in TGF-β signaling, their functional roles, and their clinical relevance in CRC. We investigate the possibility of ncRNAs as targets for detection, prognosis, and therapy. Additionally, we explore the interaction of TGF-β and other pathways in CRC and the role of ncRNAs within this intricate network. As we unveil the intricate regulatory function of ncRNAs in the TGF-β signaling in CRC, we gain valuable insights into the disease's pathogenesis. Incorporating these discoveries into clinical settings holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of CRC patients. This comprehensive review underscores the ever-evolving landscape of ncRNA research in CRC and the potential for novel interventions in the battle against this formidable disease.
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Affiliation(s)
- Khalid Saad Alharbi
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia.
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16
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Xu C, Xu P, Zhang J, He S, Hua T, Huang A. Research progress and perspectives of noncoding RNAs in adrenocortical carcinoma: A review. Medicine (Baltimore) 2024; 103:e36908. [PMID: 38277554 PMCID: PMC10817030 DOI: 10.1097/md.0000000000036908] [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: 10/04/2023] [Accepted: 12/18/2023] [Indexed: 01/28/2024] Open
Abstract
Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy. Although surgery can cure localized disease, but the majority of patients experience recurrence of ACC. The 5-year survival rate of patients with metastatic ACC is <15%, and the prognosis is poor. Therefore, it is urgent to explore the potential diagnostic markers and therapeutic targets for ACC. Recently, it has been proved that non-coding RNA (ncRNAs) is widely involved in pathological and physiological processes, including tumorigenesis and development. Aberrantly expressed ncRNAs have been found to be involved in the pathogenesis of ACC. Here, we summarized the expression patterns and the molecular mechanism of the involvement of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in ACC development. To explore the clinical value of ncRNAs as noninvasive biomarkers of ACC, we also displayed the relationship between the expression level of ncRNAs and the diagnosis and prognosis of patients with ACC.
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Affiliation(s)
- Changfen Xu
- Department of Gynecology and Obstetrics, Hangzhou Lin’an TCM Hospital, Lin’an District, Hangzhou, China
| | - Peiyao Xu
- Department of Gynecology and Obstetrics, Hangzhou Lin’an TCM Hospital, Lin’an District, Hangzhou, China
| | - Jiaqi Zhang
- Department of Gynecology and Obstetrics, Hangzhou Lin’an TCM Hospital, Lin’an District, Hangzhou, China
| | - Sheng He
- Department of Gynecology and Obstetrics, Hangzhou Lin’an TCM Hospital, Lin’an District, Hangzhou, China
| | - Tingting Hua
- Department of Gynecology and Obstetrics, Hangzhou Lin’an TCM Hospital, Lin’an District, Hangzhou, China
| | - Aiwu Huang
- Department of Gynecology and Obstetrics, Hangzhou Lin’an TCM Hospital, Lin’an District, Hangzhou, China
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17
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Suleiman AA, Al-Chalabi R, Shaban SA. Integrative role of small non-coding RNAs in viral immune response: a systematic review. Mol Biol Rep 2024; 51:107. [PMID: 38227137 DOI: 10.1007/s11033-023-09141-6] [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: 07/06/2023] [Accepted: 12/11/2023] [Indexed: 01/17/2024]
Abstract
Various viruses cause viral infection, and these viruses have different microscopic sizes, genetic material, and morphological forms. Due to a viral infection, the host body induces defense mechanisms that activate the innate and adaptive immune system. sncRNAs are involved in various biological processes and play an essential role in antiviral response in viruses including ZIKV, HCV, DENV, SARS-CoV, and West Nile virus, and regulate the complex interactions between the viruses and host cells. This review discusses the role of miRNAs, siRNAs, piRNAs, and tiRNAs in antiviral response. Cellular miRNAs bind with virus mRNA and perform their antiviral response in multiple viruses. However, the chemical modifications of miRNA necessary to avoid nuclease attack, which is then involved with intracellular processing, have proven challenging for therapeutic replacement of miRNAs. siRNAs have significant antiviral responses by targeting any gene of interest along the correct nucleotide of targeting mRNA. Due to this ability, siRNAs have valuable characteristics in antiviral response for therapeutic purposes. Additionally, the researchers noted the involvement of piRNAs and tiRNAs in the antiviral response, yet their findings were deemed insignificant.
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Affiliation(s)
| | | | - Semaa A Shaban
- Biology Department, College of Sciences, Tikrit University, Tikrit, Iraq
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18
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Jiang W, Zhu X, Bo J, Ma J. Screening of Immune-related lncRNAs in Lung Adenocarcinoma and Establishing a Survival Prognostic Risk Prediction Model. Comb Chem High Throughput Screen 2024; 27:1175-1190. [PMID: 37711103 DOI: 10.2174/1386207326666230913120523] [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: 03/27/2023] [Revised: 06/12/2023] [Accepted: 07/26/2023] [Indexed: 09/16/2023]
Abstract
OBJECTIVE This study aimed to improve lung adenocarcinoma (LUAD) prognosis prediction based on a signature of immune-related long non-coding RNAs (lncRNAs). METHODS LUAD samples from the TCGA database were divided into the immunity_H group and the immunity_L group. Differentially expressed RNAs (DERs) between the two groups were identified. Optimized immune-related lncRNAs combination was obtained using LASSO Cox regression. A prognostic risk prediction (RS) model was built and further validated in the training and validation datasets. A network among lncRNAs in the RS model, their co-expressed DERs, and the related KEGG pathways were established. Critical lncRNAs were validated in LUAD tissue samples. RESULTS In total, 255 DERs were obtained, and 11 immune-related lncRNAs were significantly related to prognosis. Six lncRNAs were demonstrated as an optimal combination for building the RS model, including LINC00944, LINC00930, LINC00607, LINC00582, LINC00543, and LINC00319. The KM curve and ROC curve revealed the RS model to be a reliable indicator for LUAD prognosis. LINC00944 and LINC00582 showed a co-expression relationship with the MS4A1. LINC00944, LINC00582, and MS4A1 were successfully validated in LUAD samples. CONCLUSION We have established a promising LUAD patient survival prediction model based on six immune-related lncRNAs. For LUAD patients, this prognostic model could guide personalized treatment.
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Affiliation(s)
- Wenxia Jiang
- School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Xuyou Zhu
- Department of Pathology, Tongji Hospital of Tongji University, Shanghai, 20065, China
| | - Jiaqi Bo
- Department of Pathology, Tongji Hospital of Tongji University, Shanghai, 20065, China
| | - Jun Ma
- Department of Nephrology, Jing'an District Center Hospital of Shanghai, Fudan University, Shanghai, 200040, China
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Wang C, Liu Y, Cui D, Jiang Y, Li L. The critical roles of lnc-GLYATL2-2/PD-L1 axis in immune microenvironment and the clinical value of intracranial chordomas. Am J Cancer Res 2023; 13:6313-6332. [PMID: 38187065 PMCID: PMC10767344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 12/15/2023] [Indexed: 01/09/2024] Open
Abstract
Intracranial chordomas (ICs) are associated with a poor prognosis due to low total resection rates and high recurrence rates. However, the role of immunotherapy in ICs remains unknown. RNA sequencing and immunohistochemical staining were performed on IC tissues and normal tissues, and the long noncoding RNA (lncRNA) lnc-GLYATL2-2 was identified. The results indicated that high expression of lnc-GLYATL2-2 was positively correlated with the tumor-infiltrating lymphocyte (TIL) markers CD4 and Foxp3, negatively correlated with CD8, and positively correlated with the expression of the immune checkpoint molecules programmed death receptor-1 (PD-1) and programmed death ligand 1 (PD-L1). Additionally, Kaplan-Meier and univariate or multivariate Cox regression analyses revealed the predictive value of lnc-GLYATL2-2 for survival based on clinical data from patients with ICs. A high expression level of lnc-GLYATL2-2 is potentially correlated with a suppressive tumor immune microenvironment and adverse clinical outcomes in IC patients. Mechanistically, the upregulation of lnc-GLYATL2-2 can result in increased cytoplasmic levels of ELAVL1, leading to enhanced binding to the 3'-UTR of PD-L1 mRNA and maintenance of its stability. In contrast, lnc-GLYATL2-2 can directly interact with the PD-L1 protein to prevent degradation, thereby promoting high levels of PD-L1 expression simultaneously at the transcriptional and translational levels in chordoma cells. These results provide a new perspective on the diagnosis and prognosis of ICs and provide theoretical evidence for immunotherapy in patients with ICs.
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Affiliation(s)
- Chengbin Wang
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai 200072, China
| | - Yingliang Liu
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai 200072, China
| | - Daming Cui
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai 200072, China
| | - Yang Jiang
- Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai 200072, China
| | - Li Li
- Hospital for Chronic Neurological Diseases, Xi’an International Meidical Center Hospital Affiliated to Northwest UniversityXi’an 710000, Shaanxi, China
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Ren H, Zheng J, Zhu Y, Wang L, Liu J, Xu H, Dong J, Zhang S. Comprehensive analysis of cuproptosis-related long non-coding RNAs in prognosis, immune microenvironment infiltration and chemotherapy response of hepatocellular carcinoma. Medicine (Baltimore) 2023; 102:e36611. [PMID: 38115286 PMCID: PMC10727658 DOI: 10.1097/md.0000000000036611] [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: 07/15/2023] [Revised: 11/17/2023] [Accepted: 11/21/2023] [Indexed: 12/21/2023] Open
Abstract
The objective of this study is to explore the relationship between cuproptosis-related long noncoding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). RNA-seq data, including lncRNAs and related clinical information of HCC patients, were downloaded from The Cancer Genome Atlas database. A signature composed 3 cuproptosis-related lncRNAs was constructed by LASSO analysis, and HCC patients were classified into high- and low-risk groups. Patients in the high-risk group had a poorer prognosis compared with the low-risk group. Univariate Cox and multivariate Cox regression analyses confirmed that the signature model was an independent risk factor compared to other clinical biomarkers. Furthermore, gene set enrichment analysis indicated that metabolism-related pathways were enriched in low-risk group, including drug metabolism, and fatty acid metabolism. Further research demonstrated that there were markedly differences in drug response between the high- and low-risk group. Immune related analysis showed that the most type of immune cells and immunological function in the high-risk group were different with the risk-group. Finally, TP53 mutation rate and the tumor mutational burden in the high-risk group were higher compared with the low-risk group. In conclusion, we constructed a prognostic signature based on the expression of cuproptosis-related lncRNAs to predict HCC patients' prognosis, drug response and immune microenvironment, and further research will be conducted to uncover the mechanisms.
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Affiliation(s)
- Huili Ren
- Department of Pharmacy, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianglin Zheng
- Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Zhu
- Department of Pharmacy, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Leiyun Wang
- Department of Pharmacy, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianmin Liu
- Department of Pharmacy, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongfeng Xu
- Department of Pharmacy, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Junli Dong
- Department of Pharmacy, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shaohui Zhang
- Department of Pharmacy, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Abaza T, El-Aziz MKA, Daniel KA, Karousi P, Papatsirou M, Fahmy SA, Hamdy NM, Kontos CK, Youness RA. Emerging Role of Circular RNAs in Hepatocellular Carcinoma Immunotherapy. Int J Mol Sci 2023; 24:16484. [PMID: 38003674 PMCID: PMC10671287 DOI: 10.3390/ijms242216484] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/13/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly fatal malignancy with limited therapeutic options and high recurrence rates. Recently, immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) have emerged as a new paradigm shift in oncology. ICIs, such as programmed cell death protein 1 (PD-1) inhibitors, have provided a new source of hope for patients with advanced HCC. Yet, the eligibility criteria of HCC patients for ICIs are still a missing piece in the puzzle. Circular RNAs (circRNAs) have recently emerged as a new class of non-coding RNAs that play a fundamental role in cancer pathogenesis. Structurally, circRNAs are resistant to exonucleolytic degradation and have a longer half-life than their linear counterparts. Functionally, circRNAs possess the capability to influence various facets of the tumor microenvironment, especially at the HCC tumor-immune synapse. Notably, circRNAs have been observed to control the expression of immune checkpoint molecules within tumor cells, potentially impeding the therapeutic effectiveness of ICIs. Therefore, this renders them potential cancer-immune biomarkers for diagnosis, prognosis, and therapeutic regimen determinants. In this review, the authors shed light on the structure and functional roles of circRNAs and, most importantly, highlight the promising roles of circRNAs in HCC immunomodulation and their potential as promising biomarkers and immunotherapeutic regimen determinants.
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Affiliation(s)
- Tasneem Abaza
- Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt; (T.A.); (M.K.A.E.-A.); (K.A.D.)
- Biotechnology and Biomolecular Chemistry Program, Faculty of Science, Cairo University, Giza 12613, Egypt
| | - Mostafa K. Abd El-Aziz
- Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt; (T.A.); (M.K.A.E.-A.); (K.A.D.)
- Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71631, Egypt
| | - Kerolos Ashraf Daniel
- Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt; (T.A.); (M.K.A.E.-A.); (K.A.D.)
- Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo 11835, Egypt
| | - Paraskevi Karousi
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece; (P.K.); (M.P.)
| | - Maria Papatsirou
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece; (P.K.); (M.P.)
| | - Sherif Ashraf Fahmy
- Department of Chemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Capital, Cairo 11835, Egypt;
| | - Nadia M. Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt;
| | - Christos K. Kontos
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece; (P.K.); (M.P.)
| | - Rana A. Youness
- Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt; (T.A.); (M.K.A.E.-A.); (K.A.D.)
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22
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Guo Q, Qiu P, Pan K, Chen J, Wang B, Lin J. Construction and validation of a transient receptor potential-related long noncoding RNA signature for prognosis prediction in breast cancer patients. Medicine (Baltimore) 2023; 102:e35978. [PMID: 37986367 PMCID: PMC10659707 DOI: 10.1097/md.0000000000035978] [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: 06/06/2023] [Revised: 09/05/2023] [Accepted: 10/16/2023] [Indexed: 11/22/2023] Open
Abstract
Breast cancer (BC) is the most commonly diagnosed malignancy in women around the world. Accumulating evidence suggests that transient receptor potential (TRP) channels play a significant role in tumor progression and immune cell infiltration. Hence, we conducted the study to investigate the correlation between TRP-associated lncRNAs and the prognosis of breast carcinoma. In the current study, 33 TRP-associated genes were selected from a review published by Amrita Samanta et al, and the TRP-related lncRNAs were identified by Pearson analysis. Based on the sum of the expression levels of 12 lncRNAs provided by the Cancer Genome Atlas (TCGA), a TRP-associated lncRNA signature was established by using Cox regression analysis. According to the median value of the risk score in the training set, BC patients were separated into high- and low-risk groups. Subsequently, functional enrichment analysis was conducted on the differential expression genes (DEGs) between different risk groups. The Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression (ESTIMATE) Score was calculated by ESTIMATE, and the immune cell infiltration was evaluated by ssGSEA. Finally, the immune checkpoint gene expression levels, microsatellite instability (MSI), and immunophenoscore (IPS) were further assessed. The high-risk groups exhibited lower survival rates, while the low-risk groups showed higher survival rates. As a result, the DEGs between different risk groups were highly enriched in immune cell activation and immunoregulation. Besides, the ESTIMATE scores of patients in low-risk groups were higher than those in high-risk groups. The infiltration levels of several immune cells were remarkably elevated in low-risk groups, and various immune signatures were activated with a decreased risk score. Eventually, the TRP-associated lncRNA signature was confirmed with a highly potential ability to evaluate the immunotherapy response in breast carcinoma patients. The outcomes of the current study indicated that the 12-TRP-associated-lncRNA risk model was an independent prognostic risk factor for BC patients. This risk model could be closely related to the tumor immune microenvironment in BC. Our findings will provide new insights for future immunotherapy for BC treatment.
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Affiliation(s)
- Qiaonan Guo
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Pengjun Qiu
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Kelun Pan
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jianpeng Chen
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Baiwei Wang
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Jianqing Lin
- Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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23
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Zhang L, Xu J, Li M, Chen X. The role of long noncoding RNAs in liquid-liquid phase separation. Cell Signal 2023; 111:110848. [PMID: 37557974 DOI: 10.1016/j.cellsig.2023.110848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/03/2023] [Accepted: 08/06/2023] [Indexed: 08/11/2023]
Abstract
Long noncoding RNAs (lncRNAs), which are among the most well-characterized noncoding RNAs, have attracted much attention due to their regulatory functions and potential therapeutic options in many types of disease. Liquid-liquid phase separation (LLPS), the formation of droplet condensates, is involved in various cellular processes, but the molecular interactions of lncRNAs in LLPS are unclear. In this review, we describe the research development on LLPS, including descriptions of various methods established to identify LLPS, summarize the physiological and pathological functions of LLPS, identify the molecular interactions of lncRNAs in LLPS, and present the potential applications of leveraging LLPS in the clinic. The aim of this review is to update the knowledge on the association between LLPS and lncRNAs, which might provide a new direction for the treatment of LLPS-mediated disease.
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Affiliation(s)
- Le Zhang
- Center for Reproductive Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia, China
| | - Jinjin Xu
- Department of Imaging Medicine, The People's Hospital of the Inner Mongolia Autonomous Region, Hohhot 010017, Inner Mongolia, China
| | - Muxuan Li
- The First Clinical Medical College of Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia, China
| | - Xiujuan Chen
- Center for Reproductive Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia, China.
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24
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Lv X, Jia Y, Li J, Deng S, Yuan E. The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress. Front Pharmacol 2023; 14:1234181. [PMID: 37808187 PMCID: PMC10551162 DOI: 10.3389/fphar.2023.1234181] [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: 06/03/2023] [Accepted: 09/12/2023] [Indexed: 10/10/2023] Open
Abstract
Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail. Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated. Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways. Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy.
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Affiliation(s)
- Xuefeng Lv
- Department of Laboratory Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yanyan Jia
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jinpeng Li
- Department of Laboratory Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Shu Deng
- Department of Laboratory Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Enwu Yuan
- Department of Laboratory Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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25
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Afra F, Mahboobipour AA, Salehi Farid A, Ala M. Recent progress in the immunotherapy of hepatocellular carcinoma: Non-coding RNA-based immunotherapy may improve the outcome. Biomed Pharmacother 2023; 165:115104. [PMID: 37393866 DOI: 10.1016/j.biopha.2023.115104] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/27/2023] [Accepted: 06/28/2023] [Indexed: 07/04/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second most lethal cancer and a leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) significantly improved the prognosis of HCC; however, the therapeutic response remains unsatisfactory in a substantial proportion of patients or needs to be further improved in responders. Herein, other methods of immunotherapy, including vaccine-based immunotherapy, adoptive cell therapy, cytokine delivery, kynurenine pathway inhibition, and gene delivery, have been adopted in clinical trials. Although the results were not encouraging enough to expedite their marketing. A major proportion of human genome is transcribed into non-coding RNAs (ncRNAs). Preclinical studies have extensively investigated the roles of ncRNAs in different aspects of HCC biology. HCC cells reprogram the expression pattern of numerous ncRNAs to decrease the immunogenicity of HCC, exhaust the cytotoxic and anti-cancer function of CD8 + T cells, natural killer (NK) cells, dendritic cells (DCs), and M1 macrophages, and promote the immunosuppressive function of T Reg cells, M2 macrophages, and myeloid-derived suppressor cells (MDSCs). Mechanistically, cancer cells recruit ncRNAs to interact with immune cells, thereby regulating the expression of immune checkpoints, functional receptors of immune cells, cytotoxic enzymes, and inflammatory and anti-inflammatory cytokines. Interestingly, prediction models based on the tissue expression or even serum levels of ncRNAs could predict response to immunotherapy in HCC. Moreover, ncRNAs markedly potentiated the efficacy of ICIs in murine models of HCC. This review article first discusses recent advances in the immunotherapy of HCC, then dissects the involvement and potential application of ncRNAs in the immunotherapy of HCC.
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Affiliation(s)
- Fatemeh Afra
- Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Ali Mahboobipour
- Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Salehi Farid
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moein Ala
- Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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26
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Abbaszadeh M, Karimi M, Rajaei S. The landscape of non-coding RNAs in the immunopathogenesis of Endometriosis. Front Immunol 2023; 14:1223828. [PMID: 37675122 PMCID: PMC10477370 DOI: 10.3389/fimmu.2023.1223828] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/02/2023] [Indexed: 09/08/2023] Open
Abstract
Endometriosis is a complex disorder that is characterized by the abnormal growth of endometrial-like tissue outside the uterus. It is associated with chronic inflammation, severe pelvic pain, infertility, and significantly reduced quality of life. Although the exact mechanism of endometriosis remains unknown, inflammation and altered immunity are considered key factors in the immunopathogenesis of the disorder. Disturbances of immune responses result in reduced clearance of regurgitated endometrial cells, which elicits oxidative stress and progression of inflammation. Proinflammatory mediators could affect immune cells' recruitment, fate, and function. Reciprocally, the activation of immune cells can promote inflammation. Aberrant expression of non-coding RNA (ncRNA) in patient and animal lesions could be suggestive of their role in endometriosis establishment. The engagement of these RNAs in regulating diverse biological processes, including inflammatory responses and activation of inflammasomes, altered immunity, cell proliferation, migration, invasion, and angiogenesis are widespread and far-reaching. Therefore, ncRNAs can be identified as a determining candidate regulating the inflammatory responses and immune system. This review aims in addition to predict the role of ncRNAs in the immunopathogenesis of endometriosis through regulating inflammation and altered immunity based on previous studies, it presents a comprehensive view of inflammation role in the pathogenesis of endometriosis.
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Affiliation(s)
| | | | - Samira Rajaei
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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27
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Fonseca-Montaño MA, Vázquez-Santillán KI, Hidalgo-Miranda A. The current advances of lncRNAs in breast cancer immunobiology research. Front Immunol 2023; 14:1194300. [PMID: 37342324 PMCID: PMC10277570 DOI: 10.3389/fimmu.2023.1194300] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 05/24/2023] [Indexed: 06/22/2023] Open
Abstract
Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related death in women worldwide. Breast cancer development and progression are mainly associated with tumor-intrinsic alterations in diverse genes and signaling pathways and with tumor-extrinsic dysregulations linked to the tumor immune microenvironment. Significantly, abnormal expression of lncRNAs affects the tumor immune microenvironment characteristics and modulates the behavior of different cancer types, including breast cancer. In this review, we provide the current advances about the role of lncRNAs as tumor-intrinsic and tumor-extrinsic modulators of the antitumoral immune response and the immune microenvironment in breast cancer, as well as lncRNAs which are potential biomarkers of tumor immune microenvironment and clinicopathological characteristics in patients, suggesting that lncRNAs are potential targets for immunotherapy in breast cancer.
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Affiliation(s)
- Marco Antonio Fonseca-Montaño
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
- Programa de Doctorado, Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | | | - Alfredo Hidalgo-Miranda
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
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28
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Sanya DRA, Onésime D. Roles of non-coding RNAs in the metabolism and pathogenesis of bladder cancer. Hum Cell 2023:10.1007/s13577-023-00915-5. [PMID: 37209205 DOI: 10.1007/s13577-023-00915-5] [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: 01/29/2023] [Accepted: 05/07/2023] [Indexed: 05/22/2023]
Abstract
Bladder cancer (BC) is featured as the second most common malignancy of the urinary tract worldwide with few treatments leading to high incidence and mortality. It stayed a virtually intractable disease, and efforts to identify innovative and effective therapies are urgently needed. At present, more and more evidence shows the importance of non-coding RNA (ncRNA) for disease-related study, diagnosis, and treatment of diverse types of malignancies. Recent evidence suggests that dysregulated functions of ncRNAs are closely associated with the pathogenesis of numerous cancers including BC. The detailed mechanisms underlying the dysregulated role of ncRNAs in cancer progression are still not fully understood. This review mainly summarizes recent findings on regulatory mechanisms of the ncRNAs, long non-coding RNAs, microRNAs, and circular RNAs, in cancer progression or suppression and focuses on the predictive values of ncRNAs-related signatures in BC clinical outcomes. A deeper understanding of the ncRNA interactive network could be compelling framework for developing biomarker-guided clinical trials.
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Affiliation(s)
- Daniel Ruben Akiola Sanya
- Micalis Institute, Diversité génomique et fonctionnelle des levures, domaine de Vilvert, Université Paris-Saclay, INRAE, AgroParisTech, 78350, Jouy-en-Josas, France.
| | - Djamila Onésime
- Micalis Institute, Diversité génomique et fonctionnelle des levures, domaine de Vilvert, Université Paris-Saclay, INRAE, AgroParisTech, 78350, Jouy-en-Josas, France
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29
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Fonseca-Montaño MA, Cisneros-Villanueva M, Coales I, Hidalgo-Miranda A. LINC00426 is a potential immune phenotype-related biomarker and an overall survival predictor in PAM50 luminal B breast cancer. Front Genet 2023; 14:1034569. [PMID: 37260772 PMCID: PMC10228735 DOI: 10.3389/fgene.2023.1034569] [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: 09/01/2022] [Accepted: 05/03/2023] [Indexed: 06/02/2023] Open
Abstract
Background: Breast cancer (BRCA) represents the most frequent diagnosed malignancy in women worldwide. Despite treatment advances, BRCAs eventually develop resistance to targeted therapies, resulting in poor prognosis. The identification of new biomarkers, like immune-related long non-coding RNAs (lncRNAs), could contribute to the clinical management of BRCA patients. In this report, we evaluated the LINC00426 expression in PAM50 BRCA subtypes from two clinical independent cohorts (BRCA-TCGA and GEO-GSE96058 datasets). Methods and results: Using Cox regression models and Kaplan-Meier survival analyses, we identified that LINC00426 expression was a consistent overall survival (OS) predictor in luminal B (LB) BRCA patients. Subsequently, differential gene expression and gene set enrichment analyses identified that LINC00426 expression was associated with different immune-related and cancer-related pathways and processes in LB BRCA. Additionally, the LINC00426 expression was correlated with the infiltration level of diverse immune cell populations, alongside immune checkpoint and cytolytic activity-related gene expression. Conclusion: This evidence suggests that LINC00426 is a potential biomarker of immune phenotype and an OS predictor in PAM50 LB BRCA.
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Affiliation(s)
- Marco Antonio Fonseca-Montaño
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
- Programa de Doctorado, Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | - Mireya Cisneros-Villanueva
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
| | - Isabelle Coales
- Centre for Host Microbiome Interactions, King’s College London, London, United Kingdom
| | - Alfredo Hidalgo-Miranda
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
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30
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Xie Y, Song X, Du D, Ni Z, Huang H. Identification of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in alimentary tract malignancies. BMC Bioinformatics 2023; 24:184. [PMID: 37142949 PMCID: PMC10161432 DOI: 10.1186/s12859-023-05314-z] [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: 02/22/2023] [Accepted: 04/28/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Alimentary tract malignancies (ATM) caused nearly one-third of all tumor-related death. Cuproptosis is a newly identified cell death pattern. The role of cuproptosis-associated lncRNAs in ATM is unknown. METHOD Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to identify prognostic lncRNAs by Cox regression and LASSO. Then a predictive nomogram was constructed based on seven prognostic lncRNAs. In addition, the prognostic potential of the seven-lncRNA signature was verified via survival analysis, the receiver operating characteristic (ROC) curve, calibration curve, and clinicopathologic characteristics correlation analysis. Furthermore, we explored the associations between the signature risk score and immune landscape, and somatic gene mutation. RESULTS We identified 1211 cuproptosis-related lncRNAs and seven survival-related lncRNAs. Patients were categorized into high-risk and low-risk groups with significantly different prognoses. ROC and calibration curve confirmed the good prediction capability of the risk model and nomogram. Somatic mutations between the two groups were compared. We also found that patients in the two groups responded differently to immune checkpoint inhibitors and immunotherapy. CONCLUSION The proposed novel seven lncRNAs nomogram could predict prognosis and guide treatment of ATM. Further research was required to validate the nomogram.
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Affiliation(s)
- Yangyang Xie
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, #453, Tiyuchang Road, Xihu District, Hangzhou, 310000, Zhejiang Province, China
| | - Xue Song
- Department of Pneumology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang Province, China
| | - Danwei Du
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, #453, Tiyuchang Road, Xihu District, Hangzhou, 310000, Zhejiang Province, China
| | - Zhongkai Ni
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, #453, Tiyuchang Road, Xihu District, Hangzhou, 310000, Zhejiang Province, China
| | - Hai Huang
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, #453, Tiyuchang Road, Xihu District, Hangzhou, 310000, Zhejiang Province, China.
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31
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Liu L, Zheng J, Xia H, Wu Q, Cai X, Ji L, Sun Y. Construction and comprehensive analysis of a curoptosis-related lncRNA signature for predicting prognosis and immune response in cervical cancer. Front Genet 2023; 14:1023613. [PMID: 36777734 PMCID: PMC9911828 DOI: 10.3389/fgene.2023.1023613] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 01/17/2023] [Indexed: 01/28/2023] Open
Abstract
Cuproptosis (copper-ion-dependent cell death) is an unprogrammed cell death, and intracellular copper accumulation, causing copper homeostasis imbalance and then leading to increased intracellular toxicity, which can affect the rate of cancer cell growth and proliferation. This study aimed to create a newly cuproptosis-related lncRNA signature that can be used to predict survival and immunotherapy in patients with cervical cancer, but also to predict prognosis in patients treated with radiotherapy and may play a role in predicting radiosensitivity. First of all, we found lncRNAs associated with cuproptosis between cervical cancer tumor tissues and normal tissues. By LASSO-Cox analysis, overlapping lncRNAs were then used to construct lncRNA signatures associated with cuproptosis, which can be used to predict the prognosis of patients, especially the prognosis of radiotherapy patients, ROC curves and PCA analysis based on cuprotosis-related lncRNA signature and clinical signatures were developed and demonstrated to have good predictive potential. In addition, differences in immune cell subset infiltration and differences in immune checkpoint expression between high-risk and low-risk score groups were analyzed, and we investigated the relationship between this signature and tumor mutation burden. In summary, we constructed a lncRNA prediction signature associated with cuproptosis. This has important clinical implications, including improving the predictive value of cervical cancer patients and providing a biomarker for cervical cancer.
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Affiliation(s)
- Li Liu
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Jianfeng Zheng
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Hongmei Xia
- Department of Gynecology, Fujian Cancer Hospital, Fuzhou, China
| | - Qiaoling Wu
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Xintong Cai
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Liyan Ji
- Geneplus-Beijing Institute, Beijing, China
| | - Yang Sun
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China,*Correspondence: Yang Sun,
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32
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Qiu P, Guo Q, Lin J, Pan K, Chen J, Ding M. An exosome-related long non-coding RNAs risk model could predict survival outcomes in patients with breast cancer. Sci Rep 2022; 12:22322. [PMID: 36566321 PMCID: PMC9789946 DOI: 10.1038/s41598-022-26894-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 12/21/2022] [Indexed: 12/25/2022] Open
Abstract
Breast cancer (BC) is one of the most frequent malignancies among women worldwide. Accumulating evidence indicates that long non-coding RNA (lncRNA) may affect BC progression. Exosomes, a class of small membrane vesicles, have been reported to promote tumor progression through transporting proteins, mRNAs, lncRNAs and some other small molecules. However, the interaction between exosome-related lncRNAs and the microenvironment of malignancies is unclear. Hence, we proceeded to investigate the relationship between exosome-related lncRNAs and BC microenvironment. 121 exosome-associated genes were extracted from ExoBCD database. Then, the Pearson analysis was used to screened out the exosome-related lncRNAs. After that, 15 exosome-related differentially expressed lncRNAs were identified by the correlation with BC prognosis. According to the sum of the expression of these 15 lncRNAs, extracted from The Cancer Genome Atlas, and the regression coefficients, an exosome-related lncRNAs signature was developed by using Cox regression analysis. With the median risk score of the training set, the patients in training and validation sets were separated to low-risk group and high-risk group. Subsequently, the lncRNA-mRNA co-expression network was constructed. The distinct enrichment pathways were compared among the different risk groups by using the R package clusterProfiler. The ESTIMATE method and ssGESA database were adopted to study the ESTIMATE Score and immune cell infiltration. Eventually, the expression of immune checkpoint associated genes, microsatellite instable and the immunophenoscore were further analyzed between different risk groups. Different risk groups exhibited different prognosis, with lower survival rate in the high-risk group. The differentially expressed genes between the different risk groups were enriched in biological processes pathways as well as immune responses. BC patients in high-risk group were identified with lower scores of ESTIMATE scores. Subsequently, we noticed that the infiltrating levels of aDCs, B cells, CD8+ T cells, iDCs, DCs, Neutrophils, macrophages, NK cells, pDCs, Tfh, T helper cells, TIL and Tregs were obvious elevated with the decreased risk score in training and validation cohorts. And some immune signatures were significantly activated with the decreased risk score in both cohorts. Eventually, the exosome-associated lncRNAs risk model was demonstrated to accurately predict immunotherapy response in patients with BC. The results of our study suggest that exosome-related lncRNAs risk model has close relationship with prognosis and immune cells infiltration in BC patients. These findings could make a great contribution to improving BC immunotherapy.
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Affiliation(s)
- Pengjun Qiu
- grid.488542.70000 0004 1758 0435Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Street, Quanzhou, China
| | - Qiaonan Guo
- grid.488542.70000 0004 1758 0435Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Street, Quanzhou, China
| | - Jianqing Lin
- grid.488542.70000 0004 1758 0435Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Street, Quanzhou, China
| | - Kelun Pan
- grid.488542.70000 0004 1758 0435Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Street, Quanzhou, China
| | - Jianpeng Chen
- grid.488542.70000 0004 1758 0435Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Street, Quanzhou, China
| | - Mingji Ding
- grid.488542.70000 0004 1758 0435Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Street, Quanzhou, China
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Guo Q, Qiu P, Pan K, Lin J. Comprehensive analysis of cuproptosis-related long non-coding RNA signature and personalized therapeutic strategy of breast cancer patients. Front Oncol 2022; 12:1081089. [PMID: 36620596 PMCID: PMC9815178 DOI: 10.3389/fonc.2022.1081089] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
Abstract
Background Breast cancer (BC) is considered to be one of the primary causes of cancer deaths in women. Cuproptosis was suggested to play an important role in tumor proliferation and tumor immune microenvironment. Therefore, an investigation was conducted to identify the relationship between cuproptosis-related long non-coding RNAs (lncRNAs) and BC prognosis. Method Based on The Cancer Genome Atlas (TCGA), nine cuproptosis-related lncRNAs were identified by Pearson's analysis and Cox regression analysis to create a cuproptosis-related lncRNA signature. Subsequently, patients with BC were divided into high-risk and low-risk groups. The Kaplan-Meier curves and a time-dependent receiver operating characteristic (ROC) analysis were employed to elucidate the predictive capability of the signature. After that, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted by Gene Set Enrichment Analysis (GSEA), and the lncRNA-mRNA co-expression network was established by Cytoscape software. Furthermore, the ESTIMATE score was calculated, and the immune cell type component analysis was conducted. Eventually, immunotherapy response analysis was applied to identify the predictive power of cuproptosis-related lncRNAs to tumor immunotherapy response, including immune checkpoint gene expression levels, tumor mutational burden (TMB), and microsatellite instability (MSI). Results Patients with BC in the low-risk groups showed better clinical outcomes. The KEGG pathways in the high-risk groups were mainly enriched in immune response and immune cell activation. Furthermore, the ESTIMATE scores were higher in the low-risk groups, and their immune cell infiltrations were dramatically different from those of the high-risk groups. The low-risk groups were shown to have higher infiltration levels of CD8+ T cells and TMB-high status, resulting in better response to immunotherapies. Conclusion The findings of this study revealed that the nine-cuproptosis-related lncRNA risk score was an independent prognostic factor for BC. This signature was a potential predictor for BC immunotherapy response. What we found will provide novel insight into immunotherapeutic treatment strategies in BC.
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A 5-Pathway Signature Predicts Prognosis Based on Immune-Derived lncRNAs in Patients with Breast Cancer. JOURNAL OF ONCOLOGY 2022; 2022:2906049. [PMID: 36545126 PMCID: PMC9763012 DOI: 10.1155/2022/2906049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 11/21/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022]
Abstract
Background Currently, predictive models were not developed based on the signaling pathway signatures of immune-related lncRNAs in breast cancer (BRCA) patients. Methods We selected unsupervised hierarchical clustering algorithm to classify patients with BRCA based on the significant immune-derived lncRNAs from the TCGA dataset. And different methods including ESTIMATE, ImmuneCellAI, and CIBERSORT were performed to evaluate the immune infiltration of tumor microenvironment. Using Lasso regression algorithm, we filtered the significant signaling pathways enriched by GSEA, GSVA, or PPI analysis to develop a prognostic model. And a nomogram integrated with clinical factors and significant pathways was constructed to predict the precise probability of overall survival (OS) of BRCA patients in the TCGA dataset (n = 1,098) and another two testing sets (n = 415). Results BRCA patients were stratified into the PC (n = 571) and GC (n = 527) subgroup with significantly different prognosis with 550 immune-related lncRNAs in the TCGA dataset. Integrated analysis revealed different immune response, oncogenic signaling, and metabolic reprograming pathways between these two subgroups. And a 5-pathway signature could predict the prognosis of BRCA patients between these two subgroups independently in the TCGA dataset, which was confirmed in another two cohorts from the GEO dataset. In the TCGA dataset, 5-year OS rate was 78% (95% CI: 73-84) vs. 82% (95% CI: 77-87) for the PC and GC group (HR = 1.63 (95% CI: 1.17-2.28), p = 0.004). The predictive power was similar in another two testing sets (HR > 1.20, p < 0.01). Finally, a nomogram is developed for clinical application, which integrated this signature and age to accurately predict the survival probability in BRCA patients. Conclusion This 5-pathway signature correlated with immune-derived lncRNAs was able to precisely predict the prognosis for patients with BRCA and provided a rich source characterizing immune-related lncRNAs and further informed strategies to target BRCA vulnerabilities.
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Hong Y, Zhang Y, Zhao H, Chen H, Yu QQ, Cui H. The roles of lncRNA functions and regulatory mechanisms in the diagnosis and treatment of hepatocellular carcinoma. Front Cell Dev Biol 2022; 10:1051306. [PMID: 36467404 PMCID: PMC9716033 DOI: 10.3389/fcell.2022.1051306] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/07/2022] [Indexed: 10/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent and deadly type of liver cancer. While the underlying molecular mechanisms are poorly understood, it is documented that lncRNAs may play key roles. Many HCC-associated lncRNAs have been linked to HBV and HCV infection, mediating gene expression, cell growth, development, and death. Studying the regulatory mechanisms and biological functions of HCC-related lncRNAs will assist our understanding of HCC pathogenesis as well as its diagnosis and management. Here, we address the potential of dysregulated lncRNAs in HCC as diagnostic and therapeutic biomarkers, and we evaluate the oncogenic or tumor-suppressive properties of these lncRNAs.
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Affiliation(s)
- Yuling Hong
- School of Clinical Medicine, Jining Medical University, Jining, China
| | - Yunxing Zhang
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Haibo Zhao
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Hailing Chen
- School of Clinical Medicine, Jining Medical University, Jining, China
| | - Qing-Qing Yu
- Jining First People’s Hospital, Jining Medical College, Jining, China
| | - Hongxia Cui
- Jining First People’s Hospital, Jining Medical College, Jining, China
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Xu QS, Shen ZZ, Yuan LQ. Identification and validation of a novel cuproptosis-related lncRNA signature for prognosis and immunotherapy of head and neck squamous cell carcinoma. Front Cell Dev Biol 2022; 10:968590. [PMID: 36467424 PMCID: PMC9712781 DOI: 10.3389/fcell.2022.968590] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 10/28/2022] [Indexed: 10/08/2024] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent and heterogeneous malignancy with a dismal overall survival rate. Nevertheless, the effective biomarkers remain ambiguous and merit further investigation. Cuproptosis is a novel defined pathway of programmed cell death that contributes to the progression of cancers. Meanwhile, long non-coding RNAs (lncRNAs) play a crucial role in the biological process of tumors. Nevertheless, the prognostic value of cuproptosis-related lncRNAs in HNSCC is still obscure. This study aimed to develop a new cuproptosis-related lncRNAs (CRLs) signature to estimate survival and tumor immunity in patients with HNSCC. Herein, 620 cuproptosis-related lncRNAs were identified from The Cancer Genome Atlas database through the co-expression method. To construct a risk model and validate the accuracy of the results, the samples were divided into two cohorts randomly and equally. Subsequently, a prognostic model based on five CRLs was constructed by the Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm. In addition, the prognostic potential of the five-CRL signature was verified via Cox regression, survival analysis, the receiver operating characteristic (ROC) curve, nomogram, and clinicopathologic characteristics correlation analysis. Furthermore, we explored the associations between the signature risk score (RS) and immune landscape, somatic gene mutation, and drug sensitivity. Finally, we gathered six clinical samples and different HNSCC cell lines to validate our bioinformatics results. Overall, the proposed novel five-CRL signature can predict prognosis and assess the efficacy of immunotherapy and targeted therapies to prolong the survival of patients with HNSCC.
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Affiliation(s)
- Qiu-Shuang Xu
- National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zheng-Zhong Shen
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Ling-Qing Yuan
- National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
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Guo P, Wang P, Liu L, Wang P, Qu Z, Yu Z, Liu N. A novel
N7
‐methylguanosine‐related long noncoding
RNAs
signature for predicting prognosis and immune microenvironment in gastric cancer patients. PRECISION MEDICAL SCIENCES 2022. [DOI: 10.1002/prm2.12087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Affiliation(s)
- Peisen Guo
- College of Public Health Zhengzhou University Zhengzhou People's Republic of China
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Jinming Avenue North Section Henan University Kaifeng People's Republic of China
| | - Panpan Wang
- College of Public Health Zhengzhou University Zhengzhou People's Republic of China
| | - Limin Liu
- College of Public Health Zhengzhou University Zhengzhou People's Republic of China
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Jinming Avenue North Section Henan University Kaifeng People's Republic of China
| | - Peixi Wang
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Jinming Avenue North Section Henan University Kaifeng People's Republic of China
| | - Zhi Qu
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Jinming Avenue North Section Henan University Kaifeng People's Republic of China
| | - Zengli Yu
- College of Public Health Zhengzhou University Zhengzhou People's Republic of China
| | - Nan Liu
- College of Public Health Zhengzhou University Zhengzhou People's Republic of China
- Institute of Chronic Disease Risks Assessment, School of Nursing and Health, Jinming Avenue North Section Henan University Kaifeng People's Republic of China
- Institute of Environment and Health, South China Hospital, Health Science Center Shenzhen University Shenzhen People's Republic of China
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Alptekin A, Parvin M, Chowdhury HI, Rashid MH, Arbab AS. Engineered exosomes for studies in tumor immunology. Immunol Rev 2022; 312:76-102. [PMID: 35808839 DOI: 10.1111/imr.13107] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 05/27/2022] [Indexed: 12/14/2022]
Abstract
Exosomes are a type of extracellular vesicle (EV) with diameters of 30-150 nm secreted by most of the cells into the extracellular spaces and can alter the microenvironment through cell-to-cell interactions by fusion with the plasma membrane and subsequent endocytosis and release of the cargo. Because of their biocompatibility, low toxicity and immunogenicity, permeability (even through the blood-brain barrier (BBB)), stability in biological fluids, and ability to accumulate in the lesions with higher specificity, investigators have started making designer's exosomes or engineered exosomes to carry biologically active protein on the surface or inside the exosomes as well as using exosomes to carry drugs, micro RNA, and other products to the site of interest. In this review, we have discussed biogenesis, markers, and contents of various exosomes including exosomes of immune cells. We have also discussed the current methods of making engineered and designer's exosomes as well as the use of engineered exosomes targeting different immune cells in the tumors, stroke, as well as at peripheral blood. Genetic engineering and customizing exosomes create an unlimited opportunity to use in diagnosis and treatment. Very little use has been discovered, and we are far away to reach its limits.
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Affiliation(s)
- Ahmet Alptekin
- Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
| | - Mahrima Parvin
- Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
| | | | | | - Ali S Arbab
- Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
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Makler A, Narayanan R, Asghar W. An Exosomal miRNA Biomarker for the Detection of Pancreatic Ductal Adenocarcinoma. BIOSENSORS 2022; 12:831. [PMID: 36290970 PMCID: PMC9599289 DOI: 10.3390/bios12100831] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/25/2022] [Accepted: 09/29/2022] [Indexed: 06/16/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a difficult tumor to diagnose and treat. To date, PDAC lacks routine screening with no markers available for early detection. Exosomes are 40-150 nm-sized extracellular vesicles that contain DNA, RNA, and proteins. These exosomes are released by all cell types into circulation and thus can be harvested from patient body fluids, thereby facilitating a non-invasive method for PDAC detection. A bioinformatics analysis was conducted utilizing publicly available miRNA pancreatic cancer expression and genome databases. Through this analysis, we identified 18 miRNA with strong potential for PDAC detection. From this analysis, 10 (MIR31, MIR93, MIR133A1, MIR210, MIR330, MIR339, MIR425, MIR429, MIR1208, and MIR3620) were chosen due to high copy number variation as well as their potential to differentiate patients with chronic pancreatitis, neoplasms, and PDAC. These 10 were examined for their mature miRNA expression patterns, giving rise to 18 mature miRs for further analysis. Exosomal RNA from cell culture media was analyzed via RTqPCR and seven mature miRs exhibited statistical significance (miR-31-5p, miR-31-3p, miR-210-3p, miR-339-5p, miR-425-5p, miR-425-3p, and miR-429). These identified biomarkers can potentially be used for early detection of PDAC.
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Affiliation(s)
- Amy Makler
- Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA
- Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Ramaswamy Narayanan
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA
- Department of Biology, University of North Florida, Jacksonville, FL 32224, USA
| | - Waseem Asghar
- Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA
- Department of Computer & Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA
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Wang O, Shi D, Li Y, Zhou X, Yan H, Yao Q. lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels. Front Oncol 2022; 12:912882. [PMID: 36059706 PMCID: PMC9428707 DOI: 10.3389/fonc.2022.912882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 07/18/2022] [Indexed: 12/09/2022] Open
Abstract
Background Early diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progression of colorectal cancer. It is of great value and clinical significance to explore lncRNAs as candidate diagnostic biomarkers in colorectal cancer. Methods Based on the within-sample relative expression levels of lncRNA pairs, we identified a group of candidate diagnostic biomarkers for colorectal cancer. In addition, we validated it in independent datasets produced by different laboratories and different platforms. We also tested it in colorectal cancer tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). Results A biomarker consisting of six lncRNA pairs including nine lncRNAs was identified for the diagnosis of colorectal cancer. For a total of 950 cancer samples and 247 non-cancer samples, both of the sensitivity and specificity could achieve approximately 90%. For adenoma samples, the accuracy could achieve 73%. For normal tissues from inflammatory bowel disease patients, 93% (14/15) were correctly classified as non-cancer. Furthermore, the lncRNA pair biomarker showed excellent performance in all clinical stages; even in the early stage, the accuracy could achieve 87% and 82% in stage I and II. Meanwhile, the biomarker was also robust to the microsatellite instability status. More importantly, we measured the biomarker in 35 colorectal cancer and 30 cancer-adjacent tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). The accuracy could achieve 93.3% (70/75). Specially, even in early-stage tumors (I and II), the accuracy could also achieve 90.9% (30/33). The enrichment analysis revealed that these lncRNAs were involved in highly associated cancer pathways and immune-related pathways. Immune analysis showed that these marker lncRNAs were associated with multiple immune cells, implying that they might be involved in the regulation of immune cell functions in colorectal cancer. Most of the biomarker lncRNAs were also differentially expressed between the mutant group and wild-type group of colorectal cancer driver genes. Conclusion We identified and validated six lncRNA pairs including nine lncRNAs as a biomarker for assisting in the diagnosis of colorectal cancer.
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Affiliation(s)
- Ouxi Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
| | - Di Shi
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Yaqi Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiaoyan Zhou
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
- *Correspondence: Xiaoyan Zhou, ; Haidan Yan, ; Qianlan Yao,
| | - Haidan Yan
- Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China
- *Correspondence: Xiaoyan Zhou, ; Haidan Yan, ; Qianlan Yao,
| | - Qianlan Yao
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
- *Correspondence: Xiaoyan Zhou, ; Haidan Yan, ; Qianlan Yao,
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Sousa DP, Conde J. Gold Nanoconjugates for miRNA Modulation in Cancer Therapy: From miRNA Silencing to miRNA Mimics. ACS MATERIALS AU 2022; 2:626-640. [PMID: 36397876 PMCID: PMC9650716 DOI: 10.1021/acsmaterialsau.2c00042] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/20/2022] [Accepted: 07/25/2022] [Indexed: 12/03/2022]
Abstract
![]()
Cancer is a major healthcare burden and cause of death
worldwide,
with an estimated 19.3 million new cancer cases and 10 million cancer
deaths globally only in 2020. While several anticancer therapeutics
are available to date, many of these still show low treatment efficacy
and high off-target effects and adverse reactions. This prompts a
serious need to develop novel therapies that can decrease the side
effects and increase treatment efficacy. MicroRNAs (miRNAs) can have
a role in tumor development and progression, making them important
targets for the improvement of anticancer therapies. In this context,
gold nanoparticles have been widely studied for different clinical
applications due to their biocompatibility and possibility of customization,
and gold nanoconjugates targeting miRNAs are being developed for cancer
diagnosis and treatment. Here we summarize the research developed
so far and how it can contribute to cancer treatment, discuss how
it can be improved, and present the current challenges and future
perspectives on their design and application.
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Affiliation(s)
- Diana P. Sousa
- NOVA Medical School
- Faculdade de Ciências Médicas, NMS
- FCM, Universidade Nova de Lisboa, Lisboa 1169-056, Portugal
- ToxOmics, NOVA Medical School
- Faculdade de Ciências Médicas, NMS
- FCM, Universidade Nova de Lisboa, Lisboa 1169-056, Portugal
| | - João Conde
- NOVA Medical School
- Faculdade de Ciências Médicas, NMS
- FCM, Universidade Nova de Lisboa, Lisboa 1169-056, Portugal
- ToxOmics, NOVA Medical School
- Faculdade de Ciências Médicas, NMS
- FCM, Universidade Nova de Lisboa, Lisboa 1169-056, Portugal
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Parashar D, Singh A, Gupta S, Sharma A, Sharma MK, Roy KK, Chauhan SC, Kashyap VK. Emerging Roles and Potential Applications of Non-Coding RNAs in Cervical Cancer. Genes (Basel) 2022; 13:genes13071254. [PMID: 35886037 PMCID: PMC9317009 DOI: 10.3390/genes13071254] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 12/06/2022] Open
Abstract
Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome's composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR-Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC.
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Affiliation(s)
- Deepak Parashar
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, MI 53226, USA
- Correspondence: (D.P.); (V.K.K.); Tel.: +1-414-439-8089 (D.P.); +1-956-296-1738 (V.K.K.)
| | - Anupam Singh
- Department of Biotechnology, GLA University, Mathura 281406, Uttar Pradesh, India; (A.S.); (S.G.)
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura 281406, Uttar Pradesh, India; (A.S.); (S.G.)
| | - Aishwarya Sharma
- Sri Siddhartha Medical College and Research Center, Tumkur 572107, Karnataka, India;
| | - Manish K. Sharma
- Department of Biotechnology, IP College, Bulandshahr 203001, Uttar Pradesh, India;
| | - Kuldeep K. Roy
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun 248007, Uttarakhand, India;
| | - Subhash C. Chauhan
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Vivek K. Kashyap
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Correspondence: (D.P.); (V.K.K.); Tel.: +1-414-439-8089 (D.P.); +1-956-296-1738 (V.K.K.)
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Zhong X, He X, Wang Y, Hu Z, Huang H, Zhao S, Zhang H, Wei P, Li D. Construction of a prognostic glycolysis-related lncRNA signature for patients with colorectal cancer. Cancer Med 2022; 12:930-948. [PMID: 35616307 PMCID: PMC9844662 DOI: 10.1002/cam4.4851] [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: 02/25/2022] [Revised: 04/27/2022] [Accepted: 05/04/2022] [Indexed: 01/26/2023] Open
Abstract
Aerobic glycolysis is a common metabolic phenotype in tumors that helps cancer cells adjust to severe living conditions and can aid metastasis in several types of carcinomas, including colorectal cancer (CRC). Long non-coding RNAs (lncRNAs) can influence tumor biology and have been previously used to assess patients' outcomes and to identify potential therapeutic targets. However, despite the importance of glycolysis-related lncRNAs (GRLs) in the development of CRC, studies on their use as prognostic markers are still limited. Herein, we applied a series of bioinformatic analyses to screen potential prognostic lncRNAs for colorectal cancer. Out of all lncRNAs screened, nine GRLs were selected to constitute a prognostic signature. Based on the signature, two molecular subtypes were classified with distinct prognostic outcomes and excellent diagnostic accuracy (The 1-, 3- and 5-year AUC are 0.756, 0.716, and 0.721, respectively). The prognostic value of this signature was further validated using another cohort. The enriched molecular pathways, immune infiltration, and mutation landscape were also significantly different between the two groups. The different drug sensitivity results between the two groups suggest a potential strategy for precise treatment. Furthermore, we confirmed that AFAP1-AS1 could regulate aerobic glycolysis and metastasis of CRC cells. Overall, we developed a glycolysis-related lncRNA (GRL) signature and suggested that this signature could offer a predictive value and identify potential therapeutic targets for cancer therapy.
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Affiliation(s)
- Xinyang Zhong
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina,Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina
| | - Xuefeng He
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina,Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina
| | - Yaxian Wang
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina,Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina
| | - Zijuan Hu
- Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina,Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina,Cancer Institute, Fudan University Shanghai Cancer CenterShanghaiChina,Institute of PathologyFudan UniversityShanghaiChina
| | - Huixia Huang
- Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina,Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina,Cancer Institute, Fudan University Shanghai Cancer CenterShanghaiChina,Institute of PathologyFudan UniversityShanghaiChina
| | - Senlin Zhao
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina,Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina
| | - Hong Zhang
- Colorectal Tumor Surgery Ward, Department of General SurgeryShengjing Hospital of China Medical UniversityShenyangPeople's Republic of China
| | - Ping Wei
- Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina,Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina,Cancer Institute, Fudan University Shanghai Cancer CenterShanghaiChina,Institute of PathologyFudan UniversityShanghaiChina
| | - Dawei Li
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina,Department of OncologyShanghai Medical College Fudan UniversityShanghaiChina
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Xie J, Tian W, Tang Y, Zou Y, Zheng S, Wu L, Zeng Y, Wu S, Xie X, Xie X. Establishment of a Cell Necroptosis Index to Predict Prognosis and Drug Sensitivity for Patients With Triple-Negative Breast Cancer. Front Mol Biosci 2022; 9:834593. [PMID: 35601830 PMCID: PMC9117653 DOI: 10.3389/fmolb.2022.834593] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 04/04/2022] [Indexed: 12/25/2022] Open
Abstract
Background: Necroptosis has been an alternatively identified mechanism of programmed cancer cell death, which plays a significant role in cancer. However, research about necroptosis-related long noncoding RNAs (lncRNAs) in cancer are still few. Moreover, the potentially prognostic value of necroptosis-related lncRNAs and their correlation with the immune microenvironment remains unclear. The present study aimed to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship to immune microenvironment in triple-negative breast cancer (TNBC). Methods: The RNA expression matrix of patients with TNBC was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Finally, 107 patients of GSE58812, 159 patients of TCGA, and 143 patients of GSE96058 were included. Necroptosis-related lncRNAs were screened by Cox regression and Pearson correlation analysis with necroptosis-related genes. By LASSO regression analysis, nine necroptosis-related lncRNAs were employed, and a cell necroptosis index (CNI) was established; then, we evaluated its prognostic value, clinical significance, pathways, immune infiltration, and chemotherapeutics efficacy. Results: Based on the CNI value, the TNBC patients were divided into high- and low-CNI groups, and the patients with high CNI had worse prognosis, more lymph node metastasis, and larger tumor (p < 0.05). The receiver operating characteristic (ROC) analysis showed that the signature performed well. The result of the infiltration proportion of different immune cell infiltration further explained that TNBC patients with high CNI had low immunogenicity, leading to poor therapeutic outcomes. Moreover, we found significant differences of the IC50 values of various chemotherapeutic drugs in the two CNI groups, which might provide a reference to make a personalized chemotherapy for them. Conclusion: The novel prognostic marker CNI could not only precisely predict the survival probability of patients with TNBC but also demonstrate a potential role in antitumor immunity and drug sensitivity.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xinhua Xie
- *Correspondence: Xinhua Xie, ; Xiaoming Xie,
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LncRNA MNX1-AS1: A novel oncogenic propellant in cancers. Biomed Pharmacother 2022; 149:112801. [PMID: 35290890 DOI: 10.1016/j.biopha.2022.112801] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/03/2022] [Accepted: 03/07/2022] [Indexed: 11/23/2022] Open
Abstract
To date, recent studies have shown that long non-coding RNAs (lncRNAs) are key players in gene regulation processes involved in cancer pathogenesis. In general, Motor neuron and pancreas homeobox 1-antisense RNA1 (MNX1-AS1) is highly expressed in all cancers as reported so far and exerts oncogenic effects through different mechanisms. In this review, we comprehensively summarize the detailed mechanisms of potential functions of MNX1-AS1 in different cancer types as well as the latest knowledge highlighting the potential of MNX1-AS1 as a therapeutic target for cancer. Aberrant expression of MNX1-AS1 closely correlates with clinicopathological parameters. such as lymphatic metastasis, tumor size, tumor stage, OS and DFS. Thus, MNX1-AS1 can be used as a diagnostic and prognostic biomarker or even a therapeutic prognostic target. This article reviews its function, molecular mechanism and clinical prognosis in various malignancies.
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Shan DD, Zheng QX, Wang J, Chen Z. Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression. World J Gastroenterol 2022; 28:1641-1655. [PMID: 35581965 PMCID: PMC9048787 DOI: 10.3748/wjg.v28.i16.1641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/09/2022] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.
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Affiliation(s)
- Dan-Dan Shan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qiu-Xian Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Jing Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Gao Y, Zhang N, Zeng Z, Wu Q, Jiang X, Li S, Sun W, Zhang J, Li Y, Li J, He F, Huang Z, Zhang J, Gong Y, Xie C. LncRNA PCAT1 activates SOX2 and suppresses radioimmune responses via regulating cGAS/STING signalling in non-small cell lung cancer. Clin Transl Med 2022; 12:e792. [PMID: 35415876 PMCID: PMC9005924 DOI: 10.1002/ctm2.792] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 03/10/2022] [Accepted: 03/14/2022] [Indexed: 01/03/2023] Open
Abstract
Background The expression of long non‐coding RNA (lncRNA) prostate cancer‐associated ncRNA transcripts 1 (PCAT1) is increased in non‐small cell lung cancer (NSCLC). It stimulates tumour growth and metastasis, but its role in the radioimmune responses remain unknown. We aimed to explore the impacts of PCAT1 on tumorigenesis and radioimmune responses and the underlying molecular mechanisms in NSCLC. Methods Comprehensive bioinformatics analysis was performed to identify immunosuppressive lncRNAs involved with tumour invasion in NSCLC. The expression levels of PCAT1 were analysed by in situ hybridisation in 55 paired NSCLC tissues and adjacent normal tissues. Both loss‐ and gain‐of‐function assays were performed to examine the effects of PCAT1 and SOX2 on NSCLC cell behaviours in vivo and in vitro. Bioinformatic analyses, chromatin isolation by RNA purification (ChIRP) and dual‐luciferase reporter assays were applied to validate the regulatory effects of PCAT1 on SOX2 expression. Chromatin immunoprecipitation, luciferase and rescue assays were utilised to identify the relationship between SOX2 and the cGAS/stimulator of interferon genes (STING) signalling. Results PCAT1 was immunosuppressive and related with NSCLC invasion. Increased PCAT1 was negatively correlated with immune cell infiltration in NSCLC. PCAT1 knockdown restrained proliferation, increased apoptosis, and repressed cell metastasis in vivo and in vitro. PCAT1 activated SOX2 that accelerated tumorigenesis and immunosuppression. SOX2 promoted tumour growth through inhibiting cytotoxic T‐cell immunity. Moreover, SOX2 restrained cGAS transcription and hampered downstream type I interferon (IFN)‐induced immune responses. Inhibition of PCAT1/SOX2 in collaboration with radiation further inhibited tumour growth, and initiated the cGAS/STING signalling pathway, which enhanced the immune responses of radiotherapy in NSCLC. Conclusions PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signalling‐mediated T‐cell activation. Inhibition of PCAT1 and SOX2 synergised with radiotherapy to activate the immune response and could serve as potential therapeutic targets.
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Affiliation(s)
- Yanping Gao
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Nannan Zhang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zihang Zeng
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qiuji Wu
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xueping Jiang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shuying Li
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wenjie Sun
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jianguo Zhang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yangyi Li
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jiali Li
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Fajian He
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhengrong Huang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.,Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jinfang Zhang
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China
| | - Yan Gong
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.,Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Conghua Xie
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.,Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China
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48
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Huang S, Gong N, Li J, Hong M, Li L, Zhang L, Zhang H. The role of ncRNAs in neuroblastoma: mechanisms, biomarkers and therapeutic targets. Biomark Res 2022; 10:18. [PMID: 35392988 PMCID: PMC8991791 DOI: 10.1186/s40364-022-00368-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 03/22/2022] [Indexed: 12/30/2022] Open
Abstract
Neuroblastoma (NB) is a malignant tumor in young children that originates from the neural crest of the sympathetic nervous system. Generally, NB occurs in the adrenal glands, but it can also affect the nerve tissues of the neck, chest, abdomen, and pelvis. Understanding the pathophysiology of NB and developing novel therapeutic approaches are critical. Noncoding RNAs (ncRNAs) are associated with crucial aspects of pathology, metastasis and drug resistance in NB. Here, we summarized the pretranscriptional, transcriptional and posttranscriptional regulatory mechanisms of ncRNAs involved in NB, especially focusing on regulatory pathways. Furthermore, ncRNAs with the potential to serve as biomarkers for risk stratification, drug resistance and therapeutic targets are also discussed, highlighting the clinical application of ncRNAs in NB.
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Affiliation(s)
- Shaohui Huang
- Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Naying Gong
- Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Jiangbin Li
- Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Mingye Hong
- Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Li Li
- Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China
| | - Ling Zhang
- Health Science Center, University of Texas, Houston, 77030, USA.
| | - Hua Zhang
- Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China.
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Dhasmana A, Dhasmana S, Kotnala S, Anukriti A, Kashyap VK, Shaji PD, Laskar P, Khan S, Pellicano R, Fagoonee S, Haque S, Yallapu MM, Chauhan SC, Jaggi M. A topography of immunotherapies against gastrointestinal malignancies. Panminerva Med 2022; 64:56-71. [PMID: 34664484 DOI: 10.23736/s0031-0808.21.04541-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Gastrointestinal (GI) cancers are one of the leading causes of death worldwide. Although various approaches are implemented to improve the health condition of GI patients, none of the treatment protocols promise for eradicating cancer. However, a treatment mechanism against any kind of disease condition is already existing executing inside the human body. The 'immune system' is highly efficient to detect and destroy the unfavorable events of the body including tumor cells. The immune system can restrict the growth and proliferation of cancer. Cancer cells behave much smarter and adopt new mechanisms for hiding from the immune cells. Thus, cancer immunotherapy might play a decisive role to train the immune system against cancer. In this review, we have discussed the immunotherapy permitted for the treatment of GI cancers. We have discussed various methods and mechanisms, periodic development of cancer immunotherapies, approved biologicals, completed and ongoing clinical trials, role of various biopharmaceuticals, and epigenetic factors involved in GI cancer immunotherapies.
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Affiliation(s)
- Anupam Dhasmana
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
- Department of Biosciences and Cancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, India
| | - Swati Dhasmana
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Sudhir Kotnala
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - A Anukriti
- School of Liberal Arts and Sciences, Department of Biosciences, Mody University, Rajasthan, India
| | - Vivek K Kashyap
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Poornima D Shaji
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Partha Laskar
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Sheema Khan
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging (CNR), Molecular Biotechnology Center, Turin, Italy
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia
- Bursa Uludağ University Faculty of Medicine, Görükle Campus, Nilüfer, Bursa, Turkey
| | - Murali M Yallapu
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Subhash C Chauhan
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Meena Jaggi
- School of Medicine, Department of Immunology and Microbiology, The University of Texas Rio Grande Valley, McAllen, TX, USA - meena.jaggi @utrgv.edu
- School of Medicine, South Texas Center of Excellence in Cancer Research, University of Texas Rio Grande Valley, McAllen, TX, USA
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Pandey PR, Young KH, Kumar D, Jain N. RNA-mediated immunotherapy regulating tumor immune microenvironment: next wave of cancer therapeutics. Mol Cancer 2022; 21:58. [PMID: 35189921 PMCID: PMC8860277 DOI: 10.1186/s12943-022-01528-6] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 01/31/2022] [Indexed: 12/16/2022] Open
Abstract
AbstractAccumulating research suggests that the tumor immune microenvironment (TIME) plays an essential role in regulation of tumor growth and metastasis. The cellular and molecular nature of the TIME influences cancer progression and metastasis by altering the ratio of immune- suppressive versus cytotoxic responses in the vicinity of the tumor. Targeting or activating the TIME components show a promising therapeutic avenue to combat cancer. The success of immunotherapy is both astounding and unsatisfactory in the clinic. Advancements in RNA-based technology have improved understanding of the complexity and diversity of the TIME and its effects on therapy. TIME-related RNA or RNA regulators could be promising targets for anticancer immunotherapy. In this review, we discuss the available RNA-based cancer immunotherapies targeting the TIME. More importantly, we summarize the potential of various RNA-based therapeutics clinically available for cancer treatment. RNA-dependent targeting of the TIME, as monotherapy or combined with other evolving therapeutics, might be beneficial for cancer patients’ treatment in the near future.
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