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Shan C, Liang Y, Wang K, Li P. Noncoding RNAs in cancer ferroptosis: From biology to clinical opportunity. Biomed Pharmacother 2023; 165:115053. [PMID: 37379641 DOI: 10.1016/j.biopha.2023.115053] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/16/2023] [Accepted: 06/21/2023] [Indexed: 06/30/2023] Open
Abstract
Ferroptosis is a recently discovered pattern of programmed cell death that is nonapoptotic and irondependent. It is involved in lipid peroxidation dependent on reactive oxygen species. Ferroptosis has been verified to play a crucial regulatory role in a variety of pathological courses of disease, in particularly cancer. Emerging research has highlighted the potential of ferroptosis in tumorigenesis, cancer development and resistance to chemotherapy. However, the regulatory mechanism of ferroptosis remains unclear, which limits the application of ferroptosis in cancer treatment. Noncoding RNAs (ncRNAs) are noncoding transcripts that regulate gene expression in various ways to affect the malignant phenotypes of cancer cells. At present, the biological function and underlying regulatory mechanism of ncRNAs in cancer ferroptosis have been partially elucidated. Herein, we summarize the current knowledge of the central regulatory network of ferroptosis, with a focus on the regulatory functions of ncRNAs in cancer ferroptosis. The clinical application and prospects of ferroptosis-related ncRNAs in cancer diagnosis, prognosis and anticancer therapies are also discussed. Elucidating the function and mechanism of ncRNAs in ferroptosis, along with assessing the clinical significance of ferroptosis-related ncRNAs, provides new perspectives for understanding cancer biology and treatment approaches, which may benefit numerous cancer patients in the future.
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Affiliation(s)
- Chan Shan
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China.
| | - Yan Liang
- Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China
| | - Kun Wang
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Peifeng Li
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China.
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Landry J, Shows K, Jagdeesh A, Shah A, Pokhriyal M, Yakovlev V. Regulatory miRNAs in cancer cell recovery from therapy exposure and its implications as a novel therapeutic strategy for preventing disease recurrence. Enzymes 2023; 53:113-196. [PMID: 37748835 DOI: 10.1016/bs.enz.2023.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Abstract
The desired outcome of cancer therapies is the eradication of disease. This can be achieved when therapy exposure leads to therapy-induced cancer cell death as the dominant outcome. Theoretically, a permanent therapy-induced growth arrest could also contribute to a complete response, which has the potential to lead to remission. However, preclinical models have shown that therapy-induced growth arrest is not always durable, as recovering cancer cell populations can contribute to the recurrence of cancer. Significant research efforts have been expended to develop strategies focusing on the prevention of recurrence. Recovery of cells from therapy exposure can occur as a result of several cell stress adaptations. These include cytoprotective autophagy, cellular quiescence, a reversable form of senescence, and the suppression of apoptosis and necroptosis. It is well documented that microRNAs regulate the response of cancer cells to anti-cancer therapies, making targeting microRNAs therapeutically a viable strategy to sensitization and the prevention of recovery. We propose that the use of microRNA-targeting therapies in prolonged sequence, that is, a significant period after initial therapy exposure, could reduce toxicity from the standard combination strategy, and could exploit new epigenetic states essential for cancer cells to recover from therapy exposure. In a step toward supporting this strategy, we survey the available scientific literature to identify microRNAs which could be targeted in sequence to eliminate residual cancer cell populations that were arrested as a result of therapy exposure. It is our hope that by successfully identifying microRNAs which could be targeted in sequence we can prevent disease recurrence.
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Affiliation(s)
- Joseph Landry
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
| | - Kathryn Shows
- Department of Biology, Virginia State University, Petersburg, VA, United States
| | - Akash Jagdeesh
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States
| | - Aashka Shah
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States
| | - Mihir Pokhriyal
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States
| | - Vasily Yakovlev
- Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, United States.
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Ortuño-Sahagún D, Enterría-Rosales J, Izquierdo V, Griñán-Ferré C, Pallàs M, González-Castillo C. The Role of the miR-17-92 Cluster in Autophagy and Atherosclerosis Supports Its Link to Lysosomal Storage Diseases. Cells 2022; 11:cells11192991. [PMID: 36230953 PMCID: PMC9564236 DOI: 10.3390/cells11192991] [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: 08/15/2022] [Revised: 09/08/2022] [Accepted: 09/20/2022] [Indexed: 12/24/2022] Open
Abstract
Establishing the role of non-coding RNA (ncRNA), especially microRNAs (miRNAs), in the regulation of cell function constitutes a current research challenge. Two to six miRNAs can act in clusters; particularly, the miR-17-92 family, composed of miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a is well-characterized. This cluster functions during embryonic development in cell differentiation, growth, development, and morphogenesis and is an established oncogenic cluster. However, its role in the regulation of cellular metabolism, mainly in lipid metabolism and autophagy, has received less attention. Here, we argue that the miR-17-92 cluster is highly relevant for these two processes, and thus, could be involved in the study of pathologies derived from lysosomal deficiencies. Lysosomes are related to both processes, as they control cholesterol flux and regulate autophagy. Accordingly, we compiled, analyzed, and discussed current evidence that highlights the cluster's fundamental role in regulating cellular energetic metabolism (mainly lipid and cholesterol flux) and atherosclerosis, as well as its critical participation in autophagy regulation. Because these processes are closely related to lysosomes, we also provide experimental data from the literature to support our proposal that the miR-17-92 cluster could be involved in the pathogenesis and effects of lysosomal storage diseases (LSD).
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Affiliation(s)
- Daniel Ortuño-Sahagún
- Laboratorio de Neuroinmunobiología Molecular, Instituto de Investigación en Ciencias Biomédicas (IICB) CUCS, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
- Correspondence: (D.O.-S.); (C.G.-C.)
| | - Julia Enterría-Rosales
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico
| | - Vanesa Izquierdo
- Pharmacology and Toxicology Section and Institute of Neuroscience, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08007 Barcelona, Spain
| | - Christian Griñán-Ferré
- Pharmacology and Toxicology Section and Institute of Neuroscience, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08007 Barcelona, Spain
| | - Mercè Pallàs
- Pharmacology and Toxicology Section and Institute of Neuroscience, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08007 Barcelona, Spain
| | - Celia González-Castillo
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico
- Correspondence: (D.O.-S.); (C.G.-C.)
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Khatoon E, Hegde M, Kumar A, Daimary UD, Sethi G, Bishayee A, Kunnumakkara AB. The multifaceted role of STAT3 pathway and its implication as a potential therapeutic target in oral cancer. Arch Pharm Res 2022; 45:507-534. [PMID: 35987863 DOI: 10.1007/s12272-022-01398-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 07/20/2022] [Indexed: 12/20/2022]
Abstract
Oral cancer is one of the leading causes of cancer-related deaths, and it has become a matter of serious concern due to the alarming rise in its incidence rate worldwide. Despite recent advancements in oral cancer treatment strategies, there are no significant improvements in patient's survival rate. Among the numerous cell signaling pathways involved in oral cancer development and progression, STAT3 is known to play a multifaceted oncogenic role in shaping the tumor pathophysiology. STAT3 hyperactivation in oral cancer contributes to survival, proliferation, invasion, epithelial to mesenchymal transition, metastasis, immunosuppression, chemoresistance, and poor prognosis. A plethora of pre-clinical and clinical studies have documented the role of STAT3 in the initiation and development of oral cancer and showed that STAT3 inhibition holds significant potential in the prevention and treatment of this cancer. However, to date, targeting STAT3 activation mainly involves inhibiting the upstream signaling molecules such as JAK and IL-6 receptors. The major challenge in targeting STAT3 lies in the complexity of its phosphorylation- and dimerization-independent functions, which are not affected by disrupting the upstream regulators. The present review delineates the significance of the STAT3 pathway in regulating various hallmarks of oral cancer. In addition, it highlights the STAT3 inhibitors identified to date through various preclinical and clinical studies that can be employed for the therapeutic intervention in oral cancer treatment.
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Affiliation(s)
- Elina Khatoon
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India.,DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India
| | - Mangala Hegde
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India.,DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India
| | - Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India.,DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India
| | - Uzini Devi Daimary
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India.,DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. .,NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India. .,DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Indian Institute of Technology (IIT) Guwahati, Guwahati, 781 039, Assam, India.
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Koh MZ, Ho WY, Yeap SK, Ali NM, Yong CY, Boo L, Alitheen NB. Exosomal-microRNA transcriptome profiling of Parental and CSC-like MDA-MB-231 cells in response to cisplatin treatment. Pathol Res Pract 2022; 233:153854. [PMID: 35398617 DOI: 10.1016/j.prp.2022.153854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 03/17/2022] [Accepted: 03/22/2022] [Indexed: 11/24/2022]
Abstract
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with higher risk of metastasis and cancer reoccurrence. Cisplatin is one of the potential anticancer drugs for treating TNBC, where its effectiveness remains challenged by frequent occurrence of cisplatin resistance. Since acquirement of drug resistance often being associated with presence of cancer stem cells (CSCs), investigation has been conducted, suggesting CSC-like subpopulation to be more resistant to cisplatin than their parental counterpart. On the other hand, plethora evidences showed the transmission of exosomal-miRNAs are capable of promoting drug resistance in breast cancers. In this study, we aim to elucidate the differential expression of exosomal-microRNAs profile and reveal the potential target genes in correlation to cisplatin resistance associated with CSC-like subpopulation by using TNBC cell line (MDA-MB-231). Utilizing next generation sequencing and Nanostring techniques, cisplatin-induced dysregulation of exosomal-miRNAs were evaluated in maximal for CSC-like subpopulation as compared to parental cells. Intriguingly, more oncogenic exosomal-miRNAs profile was detected from treated CSC-like subpopulation, which may correlate to enhancement of drug resistance and maintenance of CSCs. In treated CSC-like subpopulation, unique clusters of exosomal-miRNAs namely miR-221-3p, miR-196a-5p, miR-17-5p and miR-126-3p were predicted to target on six genes (ATXN1, LATS1, GSK3β, ITGA6, JAG1 and MYC), aligned with previous finding which demonstrated dysregulation of these genes in treated CSC-like subpopulation. Our results highlight the potential correlation of exosomal-miRNAs and their target genes as well as novel perspectives of the corresponding pathways that may be essential to contribute to the attenuated cytotoxicity of cisplatin in CSC-like subpopulation.
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Affiliation(s)
- May Zie Koh
- Faculty of Sciences and Engineering, University of Nottingham Malaysia, Semenyih 43500, Malaysia.
| | - Wan Yong Ho
- Faculty of Sciences and Engineering, University of Nottingham Malaysia, Semenyih 43500, Malaysia.
| | - Swee Keong Yeap
- China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Sepang 43900, Malaysia.
| | - Norlaily Mohd Ali
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia.
| | - Chean Yeah Yong
- Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Lily Boo
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia.
| | - Noorjahan Banu Alitheen
- Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.
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