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Arabi K, Nazemi Salman B, Rahimzadeh-Bajgiran F, Moghbeli M, Moghadas S, Saburi E. miRNAs in oral cancer; diagnostic and prognostic roles. Gene 2025; 951:149382. [PMID: 40049425 DOI: 10.1016/j.gene.2025.149382] [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: 11/23/2024] [Revised: 02/26/2025] [Accepted: 02/28/2025] [Indexed: 03/15/2025]
Abstract
Oral cancer (OC) has become increasingly prevalent in recent years, making it one of the most often occurring types of cancer in patients. The clinical identification of OC is usually a time-consuming procedure, and the outlook for individuals with OC is generally unfavorable, as no particular biomarkers have been established to far. The main risk factors linked to OC are high levels of tobacco and alcohol intake, together with a reduced occurrence of viral infections, such as human papillomavirus. Furthermore, there is evidence suggesting that genetic characteristics that can be passed down from parents to offspring play a role in increasing the likelihood of getting ovarian cancer. MicroRNAs (miRNAs) are brief RNA molecules that do not code for proteins and have the ability to either repress or promote the growth of tumors during cancer development. They have been discovered to control multiple signaling pathways within cells, and their abnormal regulation has been demonstrated to be crucial in initiating and furthering the development of cancer. Additionally, they have the ability to either facilitate or impede the entire multi-stage process of cancer metastasis, including epithelial-mesenchymal transition (EMT), migration, and invasion, by selectively targeting essential genes involved in these pathways. Several microRNAs have the ability to regulate gene expression through various ways. In addition, like other types of cancer, OC has shown alterations in the expression of miRNAs, and certain miRNAs may have the ability to be used for diagnosis and treatment. The investigation of these miRNA could perhaps result in advancements in the specified instances of OC.
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Affiliation(s)
- Kimia Arabi
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
| | - Bahareh Nazemi Salman
- Department of Pediatric Dentistry, School of Dentistry, Zanjan University of Medical Sciences, Zanjan 4513956184, Iran.
| | | | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Sepehr Moghadas
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
| | - Ehsan Saburi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Hashemi M, Khoushab S, Aghmiuni MH, Anaraki SN, Alimohammadi M, Taheriazam A, Farahani N, Entezari M. Non-coding RNAs in oral cancer: Emerging biomarkers and therapeutic frontier. Heliyon 2024; 10:e40096. [PMID: 39583806 PMCID: PMC11582460 DOI: 10.1016/j.heliyon.2024.e40096] [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: 06/09/2024] [Revised: 10/13/2024] [Accepted: 11/01/2024] [Indexed: 11/26/2024] Open
Abstract
Around the world, oral cancer (OC) is a major public health problem, resulting in a significant number of deaths each year. Early detection and treatment are crucial for improving patient outcomes. Recent progress in DNA sequencing and transcriptome profiling has revealed extensive non-coding RNAs (ncRNAs) transcription, underscoring their regulatory importance. NcRNAs influence genomic transcription and translation and molecular signaling pathways, making them valuable for various clinical applications. Combining spatial transcriptomics (ST) and spatial metabolomics (SM) with single-cell RNA sequencing provides deeper insights into tumor microenvironments, enhancing diagnostic and therapeutic precision for OC. Additionally, the exploration of salivary biomarkers offers a non-invasive diagnostic avenue. This article explores the potential of ncRNAs as diagnostic and therapeutic tools for OC.
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Affiliation(s)
- Mehrdad Hashemi
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Saloomeh Khoushab
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mina Hobabi Aghmiuni
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Saeid Nemati Anaraki
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Department of Operative, Faculty of Dentistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University,Tehran, Iran
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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Sun K, Gao L, Li S, Zheng J, Zhu Z, Zhi K, Ren W. Circ-CDK8 regulates SLC7A11-mediated ferroptosis by inhibiting miR-615-5p to promote progression in oral squamous cell carcinomas. Front Pharmacol 2024; 15:1432520. [PMID: 39170701 PMCID: PMC11335485 DOI: 10.3389/fphar.2024.1432520] [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: 05/14/2024] [Accepted: 07/18/2024] [Indexed: 08/23/2024] Open
Abstract
Introduction: Ferroptosis is a new mode of programmed cell death distinct from necrosis, apoptosis, and autophagy, induced by iron-ion-dependent lipid peroxide accumulation. Circular RNAs are a class of endogenous non-coding RNAs that regulate the biological behavior of tumors. However, the role of circ-CDK8 in regulating ferroptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) remains unknown. Methods: The effect of circ-CDK8 on OSCC cell ferroptosis, migration, and invasion was evaluated using CCK-8, wound healing, transwell, reactive oxygen species (ROS), malondialdehyde (MDA), and GSH assays and Western blotting. Bioinformatics analyses and luciferase reporter assays were performed and revealed targeted relationships between circ-CDK8 and miR-615-5p, miR-615-5p and SLC7A11. Interference with circ-CDK8 expression reduced SLC7A11 expression by sponging miR-615-5p, suppressed OSCC cell migration and invasion, and promoted ferroptosis by increasing ROS, MDA, and iron levels and decreasing GSH and GPX4 levels in OSCC cells. Furthermore, in vivo, animal experiments confirmed that circ-CDK8 interference inhibited OSCC cell proliferation and SLC7A11 expression. Results: Collectively, this study revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC cells via the circ-CDK8/miR-615-5p/SLC7A11 axis, providing new insights into OSCC and a potential therapeutic strategy for OSCC.
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Affiliation(s)
- Kai Sun
- Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ling Gao
- Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
- Key Lab of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shaoming Li
- Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jingjing Zheng
- Department of Endodontics, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhuang Zhu
- Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Keqian Zhi
- Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
- Key Lab of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wenhao Ren
- Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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Umapathy VR, Natarajan PM, Swamikannu B. Molecular and Therapeutic Roles of Non-Coding RNAs in Oral Cancer-A Review. Molecules 2024; 29:2402. [PMID: 38792263 PMCID: PMC11123887 DOI: 10.3390/molecules29102402] [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: 03/15/2024] [Revised: 05/09/2024] [Accepted: 05/12/2024] [Indexed: 05/26/2024] Open
Abstract
Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs' potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.
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Affiliation(s)
- Vidhya Rekha Umapathy
- Department of Public Health Dentistry, Dr. M.G.R. Educational and Research Institute, Thai Moogambigai Dental College and Hospital, Chennai 600107, Tamil Nadu, India
| | - Prabhu Manickam Natarajan
- Department of Clinical Sciences, Centre of Medical and Bio-Allied Health Sciences and Research Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Bhuminathan Swamikannu
- Department of Prosthodontics, Sree Balaji Dental College and Hospital, Pallikaranai, BIHER, Chennai 600100, Tamil Nadu, India;
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Wang T, He M, Zhang X, Guo Z, Wang P, Long F. Deciphering the impact of circRNA-mediated autophagy on tumor therapeutic resistance: a novel perspective. Cell Mol Biol Lett 2024; 29:60. [PMID: 38671354 PMCID: PMC11046940 DOI: 10.1186/s11658-024-00571-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024] Open
Abstract
Cancer therapeutic resistance remains a significant challenge in the pursuit of effective treatment strategies. Circular RNAs (circRNAs), a class of non-coding RNAs, have recently emerged as key regulators of various biological processes, including cancer progression and drug resistance. This review highlights the emerging role of circRNAs-mediated autophagy in cancer therapeutic resistance, a cellular process that plays a dual role in cancer by promoting both cell survival and death. Increasing evidence suggests that circRNAs can modulate autophagy pathways, thereby influencing the response of cancer cells to therapeutic agents. In this context, the intricate interplay between circRNAs, autophagy, and therapeutic resistance is explored. Various mechanisms are discussed through which circRNAs can impact autophagy, including direct interactions with autophagy-related genes, modulation of signaling pathways, and cross-talk with other non-coding RNAs. Furthermore, the review delves into specific examples of how circRNA-mediated autophagy regulation can contribute to resistance against chemotherapy and radiotherapy. Understanding these intricate molecular interactions provides valuable insights into potential strategies for overcoming therapeutic resistance in cancer. Exploiting circRNAs as therapeutic targets or utilizing them as diagnostic and predictive biomarkers opens new avenues for developing personalized treatment approaches. In summary, this review underscores the importance of circRNA-mediated autophagy in cancer therapeutic resistance and proposes future directions for research in this exciting and rapidly evolving field.
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Affiliation(s)
- Ting Wang
- Department of Clinical Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Mengjie He
- Laboratory Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, 610041, China
| | - Xudong Zhang
- Department of Clinical Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Zhixun Guo
- Department of Clinical Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Pinghan Wang
- Laboratory Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, 610041, China.
| | - Fangyi Long
- Laboratory Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, 610041, China.
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Feng Y, Qi Y, Zhang Q, Zhang M. Sevoflurane inhibits oral squamous carcinoma progression by modulating the circ_0000857/miR-145-5p axis. Chem Biol Drug Des 2024; 103:e14362. [PMID: 37770418 DOI: 10.1111/cbdd.14362] [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: 05/25/2023] [Revised: 08/30/2023] [Accepted: 09/14/2023] [Indexed: 09/30/2023]
Abstract
Oral squamous cell carcinoma (OSCC) is a kind of oral malignant tumor with the highest incidence. This study investigated whether sevoflurane (SEV) inhibited OSCC cell progression by regulating circular RNA_0000857 (circ_0000857). OSCC cells were anesthetized with SEV at different concentrations. The expression of circ_0000857 and microRNA-145-5p (miR-145-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was assayed by the Cell Counting Kit-8 (CCK-8), and cell migration and invasion were examined by the wound-healing assay and transwell. Tube formation assay detected angiogenesis. Western blot was used to detect the expression of related proteins. Compared with the control group, SEV inhibited OSCC cell migration, invasion, and angiogenesis. SEV treatment significantly decreased circ_0000857 expression level, but increased miR-145-5p expression level in SCC4 and HSC3 cells. MiR-145-5p was a target of circ_0000857, and miR-145-5p inhibitor reversed the suppressing effects mediated by circ_0000857 silencing on OSCC cell migration, invasion, and angiogenesis. SEV inhibited the level of matrix metalloproteinases 2 (MMP2), MMP9, and vascular endothelial growth factor A (VEGFA) protein by regulating the circ_0000857/miR-145-5p axis. In all, SEV regulated the migration, invasion, and angiogenesis of OSCC cells through the circ_0000857/miR-145-5p axis, which provided a basis for the potential role of SEV in the treatment of OSCC.
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Affiliation(s)
- Yingbo Feng
- Department of Anesthesiology, Hospital of Stomatology, China Medical University, Shenyang City, China
| | - Yingjun Qi
- Department of Anesthesiology, Shenyang Anorectal Hospital, Shenyang City, China
| | - Qian Zhang
- Department of Anesthesiology, Hospital of Stomatology, China Medical University, Shenyang City, China
| | - Mingming Zhang
- Department of Anesthesiology, Hospital of Stomatology, China Medical University, Shenyang City, China
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Tang S, Cai L, Wang Z, Pan D, Wang Q, Shen Y, Zhou Y, Chen Q. Emerging roles of circular RNAs in the invasion and metastasis of head and neck cancer: Possible functions and mechanisms. CANCER INNOVATION 2023; 2:463-487. [PMID: 38125767 PMCID: PMC10730008 DOI: 10.1002/cai2.50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/27/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2023]
Abstract
Head and neck cancer (HNC) is the seventh most prevalent malignancy worldwide in 2020. Cancer metastasis is the main cause of poor prognosis in HNC patients. Recently, circular RNAs (circRNAs), initially thought to have no biological function, are attracting increasing attention, and their crucial roles in mediating HNC metastasis are being extensively investigated. Existing studies have shown that circRNAs primarily function through miRNA sponges, transcriptional regulation, interacting with RNA-binding proteins (RBPs) and as translation templates. Among these functions, the function of miRNA sponge is the most prominent. In this review, we summarized the reported circRNAs involved in HNC metastasis, aiming to elucidate the regulatory relationship between circRNAs and HNC metastasis. Furthermore, we summarized the latest advances in the epidemiological information of HNC metastasis and the tumor metastasis theories, the biogenesis, characterization and functional mechanisms of circRNAs, and their potential clinical applications. Although the research on circRNAs is still in its infancy, circRNAs are expected to serve as prognostic markers and effective therapeutic targets to inhibit HNC metastasis and significantly improve the prognosis of HNC patients.
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Affiliation(s)
- Shouyi Tang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Luyao Cai
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Zhen Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Dan Pan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Qing Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Yingqiang Shen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Yu Zhou
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
- State Institute of Drug/Medical Device Clinical TrialWest China Hospital of StomatologyChengduChina
| | - Qianming Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of StomatologySichuan UniversityChengduChina
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Zhou J, Jin S. Circ_0058063 Contributed to Oral Squamous Cell Carcinoma Development by Sponging miR-145 and Regulating PI3K/AKT Pathway. Mol Biotechnol 2023; 65:2049-2060. [PMID: 36928742 DOI: 10.1007/s12033-023-00715-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 03/03/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Circular RNAs (circRNAs) are key regulators of oral squamous cell carcinoma (OSCC) progression. In this study, we aimed to clarify the regulatory roles of circ_0058063 and its effect on tumorigenesis in OSCC. METHODS Quantitative real-time polymerase chain reaction was conducted to determine the expression levels of microRNA (miR)-145-5p and circ_0058063 in OSCC. Cell viability, adhesion, migration, and epithelial-mesenchymal transition (EMT) of OSCC cells were assessed using cell counting kit-8, cell adhesion, and transwell assays. Western blotting was performed to determine the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) phosphorylation levels. Xenograft tumor models were constructed to evaluate the tumorigenicity of OSCC cells in vivo. In addition, the interaction between circ_0058063 and miR-145-5p was validated via luciferase reporter and RNA immunoprecipitation assays. RESULTS Expression levels of circ_0058063 were elevated, whereas those of miR-145-5p were decreased in OSCC. Upregulation of circ_0058063 levels enhanced the viability, adhesion, migration, and EMT of OSCC cells in vitro and promoted tumorigenicity in vivo. Moreover, circ_0058063 promoted OSCC growth by upregulating the PI3K and AKT phosphorylation levels. miR-145-5p overexpression considerably inhibited the PI3K/AKT pathway and decreased OSCC cell viability, adhesion, migration, and EMT. Mechanistically, circ_0058063 sponged miR-145-5p and activated the PI3K/AKT pathway in OSCC cells. CONCLUSION Our results revealed that circ_0058063 functions as an oncogene via regulation of the PI3K/AKT pathway by targeting miR-145-5p in OSCC, suggesting its potential for OSCC diagnosis and treatment.
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Affiliation(s)
- Jie Zhou
- Department of Stomatology, Wuhan Fourth Hospital, No. 473, Hanzheng Street, Qiaokou District, Wuhan, 430030, Hubei, China
| | - Song Jin
- Department of Stomatology, Wuhan Fourth Hospital, No. 473, Hanzheng Street, Qiaokou District, Wuhan, 430030, Hubei, China.
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Dou Z, Li M, Shen Z, Jiang H, Pang X, Li T, Liang X, Tang Y. GAD1-mediated GABA elicits aggressive characteristics of human oral cancer cells. Biochem Biophys Res Commun 2023; 681:80-89. [PMID: 37774573 DOI: 10.1016/j.bbrc.2023.09.041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/12/2023] [Accepted: 09/18/2023] [Indexed: 10/01/2023]
Abstract
Studies suggest that the expression of glutamate decarboxylase 1 (GAD1), γ-aminobutyric acid (GABA), and GABA receptors are involved in tumor progression. However, the underlying mechanisms of high expression and potential functions of GAD1 and GABA in oral squamous cell carcinoma (OSCC) are not known. In this study, we found that the expressions of GAD1 and GABA were considerably increased in OSCC samples, which were closely associated with clinical stage and lymph node metastasis. The knockdown of GAD1 expression significantly inhibited the proliferation, migration and invasion abilities of OSCC cells by reducing the expression of GABA-mediated GABAB receptors, which could be reversed by exogenous GABA, but did not cause excessive OSCC cell proliferation. And GABA secreted by OSCC cells promoted M2 macrophage polarization for inhibiting anti-tumor immunity by activating GABBR1/ERK/Ca2+. In addition, GABA/GABABR promoted the proliferation and progression of OSCC xenograft tumor. Altogether, our results showed that GAD1 synthetized GABA to promote the malignant progression of OSCC and limits the anti-tumor immunity of macrophages, thereby targeting GABA can be a novel strategy for treating OSCC.
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Affiliation(s)
- Zhichao Dou
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Mao Li
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zeliang Shen
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Hongjie Jiang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xin Pang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Tianjiao Li
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xinhua Liang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Yaling Tang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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Zhu M, Chen D, Ruan C, Yang P, Zhu J, Zhang R, Li Y. CircRNAs: A Promising Star for Treatment and Prognosis in Oral Squamous Cell Carcinoma. Int J Mol Sci 2023; 24:14194. [PMID: 37762497 PMCID: PMC10532269 DOI: 10.3390/ijms241814194] [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: 08/15/2023] [Revised: 09/11/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
CircRNAs are a class of endogenous long non-coding RNAs with a single-stranded circular structure. Most circRNAs are relatively stable, highly conserved, and specifically expressed in tissue during the cell and developmental stages. Many circRNAs have been discovered in OSCC. OSCC is one of the most severe and frequent forms of head and neck cancer today, with a poor prognosis and low overall survival rate. Due to its prevalence, OSCC is a global health concern, characterized by genetic and epigenomic changes. However, the mechanism remains vague. With the advancement of biotechnology, a large number of circRNAs have been discovered in mammalian cells. CircRNAs are dysregulated in OSCC tissues and thus associated with the clinicopathological characteristics and prognosis of OSCC patients. Research studies have demonstrated that circRNAs can serve as biomarkers for OSCC diagnosis and treatment. Here, we summarized the properties, functions, and biogenesis of circRNAs, focusing on the progress of current research on circRNAs in OSCC.
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Affiliation(s)
| | | | | | | | | | - Rongxin Zhang
- Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China; (M.Z.); (D.C.); (C.R.); (J.Z.)
| | - Yan Li
- Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China; (M.Z.); (D.C.); (C.R.); (J.Z.)
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Rajendran P, Sekar R, Zahra HA, Jayaraman S, Rajagopal P, Abdallah BM, Ali EM, Abdelsalam SA, Veeraraghavan V. Salivaomics to decode non-coding RNAs in oral cancer. A narrative review. Noncoding RNA Res 2023; 8:376-384. [PMID: 37250455 PMCID: PMC10220469 DOI: 10.1016/j.ncrna.2023.05.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 05/31/2023] Open
Abstract
Oral cancer is the most debilitating disease which affects the orderly life of a human. With so much advancement in research and technology, the average life expectancy of an individual with oral cancer appears to be about 5 years. The changing trend in incidence of oral cancer among young individuals and women without tobacco habits are ascending. Non habit related oral cancer are taking centre stage and multiple factors which induce complex biology are associated in such scenarios. To decipher the aetiology and to understand the process, these cancerous conditions are to be studied at molecular level. Saliva, the most non-invasively obtained body fluid are assessed for biomarkers exclusively in liquid biopsy. This fluid gives a huge platform to study number of molecules associated with oral cancer. Non coding RNAs are transcripts with no protein coding function. They are gaining more importance in recent times. Long noncoding RNA, microRNA are major types of noncoding transcriptome that influences in progression of oral cancer. They seem to play an important role in health and disease. Apart from these, circulating tumour cells, exosomes, extracellular vesicles, antigens and other proteins can be studied from saliva. This review is aimed to update the knowledge on current biomarkers in saliva associated with oral cancer and their epigenetic role in disease progression as well recent advances in detecting these markers to identify the stage of the disease, which will help in deciding the treatment protocol.
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Affiliation(s)
- Peramaiyan Rajendran
- Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, Tamil Nadu, India
| | - Ramya Sekar
- Central Research Laboratory, Meenakshi Academy of Higher Education and Research, West K.K. Nagar, Chennai, 600 078, India
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, Tamil Nadu, India
| | - Hamad Abu Zahra
- Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
| | - Selvaraj Jayaraman
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, Tamil Nadu, India
| | - Ponnulakshmi Rajagopal
- Central Research Laboratory, Meenakshi Academy of Higher Education and Research, West K.K. Nagar, Chennai, 600 078, India
| | - Basem M. Abdallah
- Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
| | - Enas M. Ali
- Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
- Department of Botany and Microbiology, Faculty of Science, Cairo University, Cairo, 12613, Egypt
| | - Salaheldin Abdelraouf Abdelsalam
- Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia
- Department of Zoology, Faculty of Science, Assiut University, Assiut, 71515, Egypt
| | - Vishnupriya Veeraraghavan
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, Tamil Nadu, India
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12
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Xia Y, Hei N, Peng S, Cui Z. The role and mechanism of circ-BNC2 on the malignant progression of oral squamous cell carcinoma. Head Neck 2023; 45:2424-2437. [PMID: 37377048 DOI: 10.1002/hed.27442] [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: 04/17/2023] [Revised: 06/16/2023] [Accepted: 06/18/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) play a key part in the progression of oral squamous cell carcinoma (OSCC). However, the role of circ-BNC2 (circRNA ID hsa_circ_0086414) in OSCC progression is still unclear. METHODS Plasmid transfection was used to induce overexpression of circ-BNC2. RNA expression of circ-BNC2, microRNA-142-3p (miR-142-3p) and GNAS complex locus (GNAS) was detected by quantitative real-time polymerase chain reaction. Protein expression was assessed by western blot assay or immunohistochemistry assay. Cell proliferation was investigated by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and flow cytometry analysis. Cell migratory and invasive abilities and cell apoptosis were assessed by transwell assay and flow cytometry analysis, respectively. Oxidative stress was evaluated by superoxide dismutase activity detection assay, lipid peroxidation malondialdehyde assay and cellular reactive oxygen species assay. The binding relationship between miR-142-3p and circ-BNC2 or GNAS was proved by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impacts of circ-BNC2 overexpression on tumor growth in vivo were unveiled by a xenograft mouse model assay. RESULTS Circ-BNC2 expression was downregulated in OSCC tissues and cells when compared with adjacent healthy tissues and normal human oral keratinocytes. Circ-BNC2 overexpression repressed the proliferation, migration and invasion of OSCC cells but induced cell apoptosis and oxidative stress. Additionally, circ-BNC2 overexpression inhibited tumor growth in vivo. Furthermore, circ-BNC2 bound to miR-142-3p, and miR-142-3p targeted GNAS. MiR-142-3p mimic attenuated circ-BNC2 overexpression-mediated effects on the proliferation, migration, invasion, apoptosis and oxidative stress of OSCC cells. The regulation of miR-142-3p in OSCC cell tumor properties involved GNAS. Further, circ-BNC2 introduction promoted GNAS expression by inhibiting miR-142-3p. CONCLUSION Circ-BNC2 suppressed OSCC malignant progression by upregulating GNAS expression in a miR-142-3p-dependent manner, which suggested that circ-BNC2 might be a novel target for OSCC therapy.
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Affiliation(s)
- Yingjie Xia
- Department of Stomatology, Hengshui People's Hospital, Hengshui City, Hebei Province, China
| | - Naiheng Hei
- Department of Stomatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China
| | - Shixiong Peng
- Department of Stomatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China
| | - Zifeng Cui
- Department of Stomatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China
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Eslami M, Khazeni S, Khanaghah XM, Asadi MH, Ansari MA, Garjan JH, Lotfalizadeh MH, Bayat M, Taghizadieh M, Taghavi SP, Hamblin MR, Nahand JS. MiRNA-related metastasis in oral cancer: moving and shaking. Cancer Cell Int 2023; 23:182. [PMID: 37635248 PMCID: PMC10463971 DOI: 10.1186/s12935-023-03022-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 08/06/2023] [Indexed: 08/29/2023] Open
Abstract
Across the world, oral cancer is a prevalent tumor. Over the years, both its mortality and incidence have grown. Oral cancer metastasis is a complex process involving cell invasion, migration, proliferation, and egress from cancer tissue either by lymphatic vessels or blood vessels. MicroRNAs (miRNAs) are essential short non-coding RNAs, which can act either as tumor suppressors or as oncogenes to control cancer development. Cancer metastasis is a multi-step process, in which miRNAs can inhibit or stimulate metastasis at all stages, including epithelial-mesenchymal transition, migration, invasion, and colonization, by targeting critical genes in these pathways. On the other hand, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two different types of non-coding RNAs, can regulate cancer metastasis by affecting gene expression through cross-talk with miRNAs. We reviewed the scientific literature (Google Scholar, Scopus, and PubMed) for the period 2000-2023 to find reports concerning miRNAs and lncRNA/circRNA-miRNA-mRNA networks, which control the spread of oral cancer cells by affecting invasion, migration, and metastasis. According to these reports, miRNAs are involved in the regulation of metastasis pathways either by directly or indirectly targeting genes associated with metastasis. Moreover, circRNAs and lncRNAs can induce or suppress oral cancer metastasis by acting as competing endogenous RNAs to inhibit the effect of miRNA suppression on specific mRNAs. Overall, non-coding RNAs (especially miRNAs) could help to create innovative therapeutic methods for the control of oral cancer metastases.
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Affiliation(s)
- Meghdad Eslami
- Department of oral and maxillofacial surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saba Khazeni
- Department of oral and maxillofacial surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Xaniar Mohammadi Khanaghah
- Department of oral and maxillofacial surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Hossein Asadi
- Department of oral and maxillofacial surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohamad Amin Ansari
- Department of oral and maxillofacial surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Hayati Garjan
- Department of oral and maxillofacial surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mobina Bayat
- Department of Plant, Cell and Molecular Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Taghizadieh
- Department of Pathology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Pouya Taghavi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa
| | - Javid Sadri Nahand
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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14
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Li X, Tibenda JJ, Nan Y, Huang SC, Ning N, Chen GQ, Du YH, Yang YT, Meng FD, Yuan L. MiR-204-3p overexpression inhibits gastric carcinoma cell proliferation by inhibiting the MAPK pathway and RIP1/MLK1 necroptosis pathway to promote apoptosis. World J Gastroenterol 2023; 29:4542-4556. [PMID: 37621755 PMCID: PMC10445008 DOI: 10.3748/wjg.v29.i29.4542] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 05/24/2023] [Accepted: 07/05/2023] [Indexed: 08/02/2023] Open
Abstract
BACKGROUND Gastric carcinoma (GC) is the third most frequent cause of cancer-related death, highlighting the pressing need for novel clinical treatment options. In this regard, microRNAs (miRNAs) have emerged as a promising therapeutic strategy. Studies have shown that miRNAs can regulate related signaling pathways, acting as tumor suppressors or tumor promoters. AIM To explore the effect of miR-204-3p on GC cells. METHODS We measured the expression levels of miR-204-3p in GC cells using quantitative real-time polymerase chain reaction, followed by the delivery of miR-204-3p overexpression and miR-204-3p knockdown vectors into GC cells. CCK-8 was used to detect the effect of miR-204-3p on the proliferation of GC cells, and the colony formation ability of GC cells was detected by the clonal formation assay. The effects of miR-204-3p on GC cell cycle and apoptosis were detected by flow cytometry. The BABL/c nude mouse subcutaneous tumor model using MKN-45 cells was constructed to verify the effect of miR-204-3p on the tumorigenicity of GC cells. Furthermore, the study investigated the effects of miR-204-3p on various proteins related to the MAPK signaling pathway, necroptosis signaling pathway and apoptosis signaling pathway on GC cells using Western blot techniques. RESULTS Firstly, we found that the expression of miR-204-3p in GC was low. When treated with the lentivirus overexpression vector, miR-204-3p expression significantly increased, but the lentivirus knockout vector had no significant effect on miR-204-3p. In vitro experiments confirmed that miR-204-3p overexpression inhibited GC cell viability, promoted cell apoptosis, blocked the cell cycle, and inhibited colony formation ability. In vivo animal experiments confirmed that miR-204-3p overexpression inhibited subcutaneous tumorigenesis ability in BABL/c nude mice. Simultaneously, our results verified that miR-204-3p overexpression can inhibit GC cell proliferation by inhibiting protein expression levels of KRAS and p-ERK1/2 in the MAPK pathway, as well as inhibiting protein expression levels of p-RIP1 and p-MLK1 in the necroptosis pathway to promote the BCL-2/BAX/Caspase-3 apoptosis pathway. CONCLUSION MiR-204-3p overexpression inhibited GC cell proliferation by inhibiting the MAPK pathway and necroptosis pathway to promote apoptosis of GC cells. Thus, miR-204-3p may represent a new potential therapeutic target for GC.
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Affiliation(s)
- Xia Li
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- Ningxia Chinese Medicine Reserch Center, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Joanna J Tibenda
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Nan
- Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Shi-Cong Huang
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Na Ning
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Guo-Qing Chen
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yu-Hua Du
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ya-Ting Yang
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Fan-Di Meng
- Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
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15
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Dey S, Biswas B, Manoj Appadan A, Shah J, Pal JK, Basu S, Sur S. Non-Coding RNAs in Oral Cancer: Emerging Roles and Clinical Applications. Cancers (Basel) 2023; 15:3752. [PMID: 37568568 PMCID: PMC10417002 DOI: 10.3390/cancers15153752] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/29/2023] [Accepted: 07/12/2023] [Indexed: 08/13/2023] Open
Abstract
Oral cancer (OC) is among the most prevalent cancers in the world. Certain geographical areas are disproportionately affected by OC cases due to the regional differences in dietary habits, tobacco and alcohol consumption. However, conventional therapeutic methods do not yield satisfying treatment outcomes. Thus, there is an urgent need to understand the disease process and to develop diagnostic and therapeutic strategies for OC. In this review, we discuss the role of various types of ncRNAs in OC, and their promising clinical implications as prognostic or diagnostic markers and therapeutic targets. MicroRNA (miRNA), long ncRNA (lncRNA), circular RNA (circRNA), PIWI-interacting RNA (piRNA), and small nucleolar RNA (snoRNA) are the major ncRNA types whose involvement in OC are emerging. Dysregulated expression of ncRNAs, particularly miRNAs, lncRNAs, and circRNAs, are linked with the initiation, progression, as well as therapy resistance of OC via modulation in a series of cellular pathways through epigenetic, transcriptional, post-transcriptional, and translational modifications. Differential expressions of miRNAs and lncRNAs in blood, saliva or extracellular vesicles have indicated potential diagnostic and prognostic importance. In this review, we have summarized all the promising aspects of ncRNAs in the management of OC.
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Affiliation(s)
| | | | | | | | | | - Soumya Basu
- Cancer and Translational Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth (DPU), Pimpri 411033, India; (S.D.)
| | - Subhayan Sur
- Cancer and Translational Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth (DPU), Pimpri 411033, India; (S.D.)
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16
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Kabzinski J, Kucharska-Lusina A, Majsterek I. RNA-Based Liquid Biopsy in Head and Neck Cancer. Cells 2023; 12:1916. [PMID: 37508579 PMCID: PMC10377854 DOI: 10.3390/cells12141916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/17/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
Head and neck cancer (HNC) is a prevalent and diverse group of malignancies with substantial morbidity and mortality rates. Early detection and monitoring of HNC are crucial for improving patient outcomes. Liquid biopsy, a non-invasive diagnostic approach, has emerged as a promising tool for cancer detection and monitoring. In this article, we review the application of RNA-based liquid biopsy in HNC. Various types of RNA, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), circular RNA (circRNA) and PIWI-interacting RNA (piRNA), are explored as potential biomarkers in HNC liquid-based diagnostics. The roles of RNAs in HNC diagnosis, metastasis, tumor resistance to radio and chemotherapy, and overall prognosis are discussed. RNA-based liquid biopsy holds great promise for the early detection, prognosis, and personalized treatment of HNC. Further research and validation are necessary to translate these findings into clinical practice and improve patient outcomes.
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Affiliation(s)
- Jacek Kabzinski
- Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, MolecoLAB A6, Mazowiecka 5, 92-215 Lodz, Poland
| | - Aleksandra Kucharska-Lusina
- Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, MolecoLAB A6, Mazowiecka 5, 92-215 Lodz, Poland
| | - Ireneusz Majsterek
- Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, MolecoLAB A6, Mazowiecka 5, 92-215 Lodz, Poland
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17
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Liu F, Wu H, Wu G, Long J, Dai J, Wang Z. circPKD2 inhibits the glioma cell proliferation, invasion and glycolytic metabolism through regulating the miR-1278/LATS2 axis. Neurosci Lett 2023; 801:137126. [PMID: 36796622 DOI: 10.1016/j.neulet.2023.137126] [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: 09/30/2022] [Revised: 01/28/2023] [Accepted: 02/10/2023] [Indexed: 02/16/2023]
Abstract
Glioma is the most prevalent brain tumor with a poor prognosis. Circular RNA (circ) (PKD2) has been identified as a potential tumor suppressor. However, the effect of circPKD2 on glioma has been unknown. circPKD2 expression in glioma and its potential targets were analyzed by bioinformatics methods, qRT-PCR, dual luciferase reporter, RNA-pull down and RNA immunoprecipitation assays. Overall survival was analyzed by Kaplan-Meier method. The correlation of circPKD2 expression with patient's clinical characteristics was assessed by Chi-square test. Glioma cell invasion was detected by Transwell invasion assay, and cell proliferation was determined by CCK8 and EdU assays. ATP level, Lactate production, and glucose consumption were measured by commercial assay kits, and glycolysis-related protein (Ki-67, VEGF, HK2, LDHA) levels were evaluated by western blot. circPKD2 expression was downregulated in glioma, but circPKD2 overexpression inhibited the cell proliferation, invasion, and glycolytic metabolism. Besides, patients with low circPKD2 expression had a worse prognosis. circPKD2 level was correlated with distant metastasis, WHO grade, and Karnofsky, KPS score. circPKD2 acted as a sponge of miR-1278, and LATS2 was a target gene of miR-1278. Moreover, circPKD2 could target miR-1278 to up-regulate LATS2 expression to suppress the cell proliferation, invasion, and glycolytic metabolism. These findings display that circPKD2 can function as a tumor suppressor in glioma by controlling the miR-1278/LATS2 axis and provide the potential biomarkers for glioma treatment.
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Affiliation(s)
- Feng Liu
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, China
| | - Hao Wu
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, China
| | - Guangyong Wu
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, China
| | - Jun Long
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, China
| | - Jin Dai
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, China
| | - Zhifei Wang
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, China.
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18
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Cheng T, Huang F, Zhang Y, Zhou Z. Circ_0004491 stimulates guanine nucleotide-binding protein alpha subunit to inhibit the malignant progression of oral squamous cell carcinoma by sponging miR-2278. J Dent Sci 2023; 18:237-247. [PMID: 36643221 PMCID: PMC9831788 DOI: 10.1016/j.jds.2022.05.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/24/2022] [Indexed: 01/18/2023] Open
Abstract
Background/purpose Circular RNA origin recognition complex subunit 4 (circORC4; ID: hsa_circ_0004491) have been confirmed to be a novel potential biomarker of oral squamous cell carcinoma (OSCC). This study aimed to explore the molecular mechanism of circ_0004491 in OSCC progression. Materials and methods Levels of circ_0004491, microRNA (miR)-2278, guanine nucleotide-binding protein alpha subunit (GNAS), Bax, Bcl-2, E-cadherin and ki-67 were detected by quantitative real-time PCR, western blotting and immunohistochemistry. The proliferation of OSCC cells was measured using colony formation assay and EdU staining. Cell apoptosis and motility were detected by flow cytometry and transwell assays respectively. Interaction between miR-2278 and circ_0004491 or GNAS was predicted by bioinformatics analysis and confirmed via luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model was used to analyze the role of circ_0004491 in tumor growth in vivo. Results Circ_0004491 was downregulated in OSCC tissues and cell lines. Circ_0004491 overexpression suppressed the proliferation, migration and invasion whereas facilitated the apoptosis of OSCC cells. Circ_0004491 acted as a molecular sponge for miR-2278, and circ_0004491 overexpression-mediated effect was partly reversed by miR-2278 mimic in OSCC cells. MiR-2278 interacted with the 3'UTR of GNAS. Circ_0004491 contributed to GNAS level by sponging miR-2278 in OSCC cells. GNAS knockdown restored miR-2278 inhibitor-mediated effect in OSCC cells. Circ_0004491 overexpression repressed xenograft tumor growth in vivo. Conclusion Circ_0004491 can repress OSCC progression by regulation of miR-2278/GNAS axis, providing a possible circRNA-targeted therapy for OSCC.
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Affiliation(s)
- Tao Cheng
- Department of Stomatology, Hanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, Wuhan, China,Corresponding author. Department of StomatologyHanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, No. 53, Ink Lake Road, Hanyang District, Wuhan, 430050, China.
| | - Feifei Huang
- Department of Respiratory Medicine, Dongxihu District People’s Hospital of Wuhan City in Hubei Province, Wuhan, China
| | - Yin Zhang
- Department of Stomatology, Hanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, Wuhan, China
| | - Zhen Zhou
- Department of Stomatology, Hanyang Hospital Affiliated to Medical College of Wuhan University of Science and Technology, Wuhan, China
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Dai Y, Zhu Y, Xu H. circ_0004872 inhibits proliferation, invasion, and glycolysis of oral squamous cell carcinoma by sponged miR-424-5p. J Clin Lab Anal 2022; 36:e24486. [PMID: 35576499 PMCID: PMC9280002 DOI: 10.1002/jcla.24486] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/31/2022] [Accepted: 04/28/2022] [Indexed: 11/20/2022] Open
Abstract
Objective Oral squamous cell carcinoma (OSCC) is one of the most common oral malignant tumors. circ_0004872 can inhibit the progression of gastric cancer, but its effect on the growth and metastasis of OSCC is still unclear. Methods qRT‐PCR was used to detect the expression levels of circ_0004872 and miR‐424‐5p in cancer tissues of OSCC patients and adjacent normal tissues, OSCC cell lines, and human normal oral keratinocytes (HOK). CCK‐8, cell colony formation, flow cytometry, and transwell assay were used to detect cell proliferation rate, viability, apoptosis rate, and invasion ability. Use glucose/lactic acid kit to assay cell glycolysis ability. The dual‐luciferase reporter gene experiment and RIP experiment verified the relationship between circ_0004872 and miR‐424‐5p. The protein levels were examined by Western blot. Results The expression of circ_0004872 was significantly downregulated in OSCC tissues and cells, and the overexpression of circ_0004872 inhibited the proliferation, vitality, invasion, and glycolysis of OSCC cells, and promoted apoptosis. The expression of miR‐424‐5p was greatly upregulated in OSCC tissues and OSCC cells. circ_0004872 can adsorb miR‐424‐5p in OSCC cells, and circ_0004872 can reverse the promoting effect of miR‐424‐5p overexpression on the process of OSCC cells. Conclusion circ_0004872 suppresses the proliferation, invasion, and glycolysis of OSCC cells by sponged miR‐424‐5p, and promotes apoptosis, which can be used as a potential target for early diagnosis and targeted therapy of OSCC.
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Affiliation(s)
- Yinhua Dai
- Department of General Emergency, The Affiliated Stomatological Hospital of Nanchang University, Nanchang, Jiangxi Province, China.,The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, China.,Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, Jiangxi Province, China
| | - Yalin Zhu
- Department of General Emergency, The Affiliated Stomatological Hospital of Nanchang University, Nanchang, Jiangxi Province, China.,The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, China.,Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, Jiangxi Province, China
| | - Houyi Xu
- Department of General Emergency, The Affiliated Stomatological Hospital of Nanchang University, Nanchang, Jiangxi Province, China.,The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, China.,Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, Jiangxi Province, China
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20
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Lu X, Xie H. Circ_0001971 makes progress of oral squamous cell carcinoma by targeting miR‐107/FZD4 axis. Oral Dis 2022. [PMID: 35403775 DOI: 10.1111/odi.14207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 03/15/2022] [Accepted: 04/04/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Xiaopeng Lu
- Department of Stomatology Jingmen No People’s Hospital Jingmen 448000 Hubei China
| | - Hongguo Xie
- Department of Stomatology Jingmen No People’s Hospital Jingmen 448000 Hubei China
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Rong L, Chen B, Liu K, Liu B, He X, Liu J, Li J, He M, Zhu L, Liu K, Shi X, Shuai Y, Jin L. CircZDBF2 up-regulates RNF145 by ceRNA model and recruits CEBPB to accelerate oral squamous cell carcinoma progression via NFκB signaling pathway. J Transl Med 2022; 20:148. [PMID: 35365168 PMCID: PMC8973790 DOI: 10.1186/s12967-022-03347-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 03/10/2022] [Indexed: 11/26/2022] Open
Abstract
Background Oral squamous cell carcinoma (OSCC), as one of the commonest malignancies showing poor prognosis, has been increasingly suggested to be modulated by circular RNAs (circRNAs). Through GEO (Gene Expression Omnibus) database, a circRNA derived from ZDBF2 (circZDBF2) was uncovered to be with high expression in OSCC tissues, while how it may function in OSCC remains unclear. Methods CircZDBF2 expression was firstly verified in OSCC cells via qRT-PCR. CCK-8, along with colony formation, wound healing, transwell and western blot assays was performed to assess the malignant cell behaviors in OSCC cells. Further, RNA pull down assay, RIP assay, as well as luciferase reporter assay was performed to testify the interaction between circZDBF2 and RNAs. Results CircZDBF2 expressed at a high level in OSCC cells and it accelerated OSCC cell proliferation, migration, invasion as well as EMT (epithelial-mesenchymal transition) process. Further, circZDBF2 sponged miR-362-5p and miR-500b-5p in OSCC cells to release their target ring finger protein 145 (RNF145). RNF145 expressed at a high level in OSCC cells and circZDBF2 facilitated RNF145 transcription by recruiting the transcription factor CCAAT enhancer binding protein beta (CEBPB). Moreover, RNF145 activated NFκB (nuclear factor kappa B) signaling pathway and regulated IL-8 (C-X-C motif chemokine ligand 8) transcription. Conclusion CircZDBF2 up-regulated RNF145 expression by sponging miR-362-5p and miR-500b-5p and recruiting CEBPB, thereby promoting OSCC progression via NFκB signaling pathway. The findings recommend circZDBF2 as a probable therapeutic target for OSCC. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12967-022-03347-1.
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Affiliation(s)
- Liang Rong
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China
| | - Bo Chen
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China
| | - Ke Liu
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China
| | - Bingyao Liu
- Department of Stomatology, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, Jiangsu, China
| | - Xinyao He
- Department of Stomatology, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, Jiangsu, China.,Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210002, Jiangsu, China
| | - Juan Liu
- Department of Stomatology, Jinling Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Junxia Li
- Department of Stomatology, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, Jiangsu, China
| | - Maodian He
- Department of Stomatology, Jinling Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Lei Zhu
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China
| | - Ke Liu
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China
| | - Xiaolei Shi
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China
| | - Yi Shuai
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
| | - Lei Jin
- Department of Stomatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
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Circ-PKD2 promotes Atg13-mediated autophagy by inhibiting miR-646 to increase the sensitivity of cisplatin in oral squamous cell carcinomas. Cell Death Dis 2022; 13:192. [PMID: 35220397 PMCID: PMC8882170 DOI: 10.1038/s41419-021-04497-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 11/03/2021] [Accepted: 12/20/2021] [Indexed: 12/16/2022]
Abstract
Autophagy is an evolutionally conserved catabolic process that degrades cells to maintain homeostasis. Cisplatin-activated autophagy promotes the expression of circ-PKD2, which plays a role as a tumor suppressor gene in the proliferation, migration, and invasion in oral squamous cell carcinoma (OSCC). However, the role of circ-PKD2 in regulating the sensitivity of OSCC patients to cisplatin remains to be elucidated. Overexpression of circ-PKD2 increased the formation of autophagosomes in OSCC cells and activation of proteins, such as LC3 II/I. Its activation effect on autophagy was, however, alleviated by 3-MA. Bioinformatics analyses and double luciferases reporter assays conducted in this study confirmed the existence of targeted relationships between circ-PKD2 and miR-646 and miR-646 and Atg13. Functional experiments further revealed that miR-646 reversed the autophagy and apoptosis effects of circ-PKD2 in OSCC cells treated with cisplatin. In addition, circ-PKD2 promoted the expression of ATG13 by adsorption of miR-646. Its interference with Atg13 alleviated the activation effects of circ-PKD2 on autophagy and apoptosis of miR-646. Notably, the in vivo animal experiments also confirmed that circ-PKD2 inhibited tumor proliferation and activated autophagy in OSCC cells. This study provides a theoretical basis for using circ-PKD2 as a target to regulate the sensitivity of OSCC patients to cisplatin, thus increasing its chemotherapeutic effects.
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Li L, Yin Y, Nan F, Ma Z. Circ_LPAR3 promotes the progression of oral squamous cell carcinoma (OSCC). Biochem Biophys Res Commun 2022; 589:215-222. [PMID: 34922206 DOI: 10.1016/j.bbrc.2021.12.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/05/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND circ_LPAR3 is an oncogene in esophageal squamous cell carcinoma. However, its role in oral squamous cell carcinoma (OSCC) is unknown. PURPOSE To reveal the functions of circ_LPAR3 in OSCC. METHODS Online bioinformatic analysis was performed to disclose the differential expression of circ_LPAR3, VEGFC, AKT1 in OSCC and also the target predictions of miR-513b-5p. Transfection was applied in OSCC cells. RT-qPCR was used to detect the RNA expression and western blot to measure the proteins, VEGFC and phosphor-AKT1 (ser473, p-AKT1). CCK8 kit was used for viability detection and Flow cytometry for apoptosis evaluation. RNA pull-down and luciferase reporter methods were used to validate the binding sites to miR-513b-5p on circ_LPAR3, VEGFC and AKT1. OSCC mice models were established to further unveil the functions of circ_LPAR3 in OSCC in vivo. H&E staining and immunohistochemistry (CD34, VEGFC and p-AKT1) were further applied to analyze the pathological changes in association with circ_LPAR3 downregulation. RESULTS circ_LPAR3 was upregulated in OSCC. Its knockdown in cells could decrease cell survival and mobility and in mice model, could inhibit the tumor growth and angiogenesis. Circ_LPAR3 promoted VEGFC and AKT1 activity by sponging miR-513b-5p in OSCC cells. CONCLUSION Knockdown of circ_LPAR3 could inhibit the OSCC progression by sponging miR-513b-5p and activating VEGFC and AKT1.
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Affiliation(s)
- Li Li
- Department of Stomatology, PLA 983rd Hospital, Tianjin, China.
| | - Ye Yin
- Department of Stomatology, PLA 983rd Hospital, Tianjin, China.
| | - Fanglong Nan
- Department of Stomatology, PLA 983rd Hospital, Tianjin, China.
| | - Zeyu Ma
- Department of Stomatology, PLA 983rd Hospital, Tianjin, China.
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24
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Cheng Y, Ma Z, Liu S, Yang X, Li S. CircLPAR3 knockdown suppresses esophageal squamous cell carcinoma cell oncogenic phenotypes and Warburg effect through miR-873-5p/LDHA axis. Hum Exp Toxicol 2022; 41:9603271221143695. [PMID: 36484173 DOI: 10.1177/09603271221143695] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Circular RNAs (circRNAs) have been identified to participate in regulating multiple malignancies. Herein, this study aimed to explore the clinical significance, biological function, and regulatory mechanisms of circRNA lysophosphatidic acid receptor 3 (circLPAR3) in esophageal squamous cell carcinoma (ESCC) cell malignant phenotypes and Warburg effect. METHODS The qRT-PCR and Western blot were used to detect the levels of genes and proteins. Glucose uptake and lactate production were detected to determine the Warburg effect. The effects of circLPAR3 on ESCC cell proliferation, apoptosis, and metastasis were evaluated by MTT, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays. The binding interaction between miR-873-5p and circLPAR3 or lactate dehydrogenase A (LDHA) was verified using dual-luciferase reporter and RIP assays. Xenograft mice models were established to conduct in vivo analysis. RESULTS CircLPAR3 is a stable circRNA and was increased in ESCC tissues and cells. Functionally, circLPAR3 knockdown suppressed ESCC cell Warburg effect, proliferation, metastasis, and induced apoptosis in vitro, and impeded xenograft tumor growth and Warburg effect in ESCC mice models. Mechanistically, circLPAR3 served as a sponge for miR-873-5p, which targeted LDHA. Moreover, circLPAR3 could regulate LDHA expression by sponging miR-873-5p. Thereafter, rescue experiments suggested that miR-873-5p inhibition reversed the anticancer effects of circLPAR3 silencing on ESCC cells. Furthermore, miR-873-5p overexpression restrained ESCC cell Warburg effect and oncogenic phenotypes, which were abolished by LDHA up-regulation. CONCLUSION CircLPAR3 knockdown suppressed ESCC cell growth, metastasis, and Warburg effect by miR-873-5p/LDHA axis, implying a promising molecular target for ESCC therapy.
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Affiliation(s)
- Yao Cheng
- Department of Thoracic Surgery, 12480Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhenchuan Ma
- Department of Thoracic Surgery, 12480Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Shiyuan Liu
- Department of Thoracic Surgery, 12480Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xiaoping Yang
- Department of Thoracic Surgery, 12480Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Shaomin Li
- Department of Thoracic Surgery, 12480Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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Yan J, Xu H. Regulation of transforming growth factor-beta1 by circANKS1B/miR-515-5p affects the metastatic potential and cisplatin resistance in oral squamous cell carcinoma. Bioengineered 2021; 12:12420-12430. [PMID: 34781814 PMCID: PMC8810104 DOI: 10.1080/21655979.2021.2005221] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) is the most common oral cancer, with an increasing worldwide incidence and a worsening prognosis. Emerging evidence confirms that circular RNAs (circRNAs) play a critical role in tumor progression via sponging miRNAs. A previous study substantiated the function of circANKS1B in several cancers. However, its role in OSCC remains unclear. This study revealed the high expression of circANKS1B in OSCC tissues and cells. Moreover, the expression level of circANKS1B was highly positively correlated with the expression of transforming growth factor-beta1 (TGF-β1) in OSCC tissues. Additionally, overexpression of circANKS1B enhanced the protein expression of TGF-β1 in OSCC cells, while its inhibition reduced TGF-β1 protein levels. Noticeably, the loss-function of circANKS1B restrained OSCC cell invasion, migration, and epithelial to mesenchymal transition (EMT) by decreasing N-cadherin expression and enhancing E-cadherin expression. Furthermore, the knockdown of circANKS1B sensitized OSCC cells to cisplatin by suppressing cell viability and increasing cell apoptosis and caspase-3 activity. Mechanically, bioinformation software (circinteractome and starBase 3.0) and dual-luciferase reporter assays corroborated that circANKS1B could sponge miR-515-5p. Moreover, miR-515-5p could directly target TGF-β1 to suppress its expression. Importantly, inhibition of miR-515-5p or supplementation with TGF-β1 overturned the effects of circANKS1B knockdown on cell invasion, migration, and cisplatin resistance. Thus, these findings highlight that circANKS1B might act as an oncogenic gene to facilitate the metastatic potential and cisplatin resistance in OSCC by sponging miR-515-5p to regulate TGF-β1. Collectively, circANKS1B may be a promising target for therapy and overcoming chemoresistance in OSCC.
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Affiliation(s)
- Jiawei Yan
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing 410047, P.R. China
| | - Hongyan Xu
- Department of Stomatology, Shaanxi Provincial People's Hospital, Xi'an 710000, P.R. China
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CircLPAR3 Acts as an Oncogene in Oral Squamous Cell Carcinoma Through Regulating the miR-643/HMGB2 Network. Biochem Genet 2021; 60:882-898. [PMID: 34528144 DOI: 10.1007/s10528-021-10134-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 09/04/2021] [Indexed: 12/09/2022]
Abstract
The malignant progression of oral squamous cell carcinoma (OSCC) has been confirmed to be mediated by a variety of factors, including circular RNA (circRNA). However, the role of circLPAR3 in OSCC development is still unclear. 70 paired OSCC tissues and normal control tissues were obtained from 70 OSCC patients. Quantitative real-time PCR was used to detect the expression of circLPAR3, microRNA (miR)-643, and high-mobility group box 2 (HMGB2). Cell proliferation, apoptosis, metastasis and stemness were assessed using cell counting kit 8 assay, colony-formation assay, flow cytometry, transwell assay and sphere formation assay. Marker protein expression and HMGB2 protein expression were determined by western blot analysis. The interaction between miR-643 and circLPAR3 or HMGB2 was confirmed by RNA pull-down assay, dual-luciferase reporter and RIP assay. The role of circLPAR3 in OSCC tumorigenesis was explored by constructing the xenograft models. Our data showed that circLPAR3 was highly expressed in OSCC tissues and cells. CircLPAR3 silencing suppressed OSCC cell proliferation, metastasis and stemness, while promoted apoptosis. On the mechanism, we discovered that circLPAR3 could sponge miR-643 to positive regulate HMGB2. MiR-643 overexpression had an inhibition effect on OSCC progression, and its inhibitor could reverse the negative regulation of circLPAR3 knockdown on OSCC progression. In addition, overexpressed HMGB2 also reversed the suppressive effect of circLPAR3 silencing on OSCC progression. Animal experiments results showed that downregulated circLPAR3 repressed OSCC tumorigenesis in vivo. Taken together, our data showed that circLPAR3 contributed to OSCC malignant progression through regulating the miR-643/HMGB2 axis.
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27
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Qiu F, Qiao B, Zhang N, Fang Z, Feng L, Zhang S, Qiu W. Blocking circ-SCMH1 (hsa_circ_0011946) suppresses acquired DDP resistance of oral squamous cell carcinoma (OSCC) cells both in vitro and in vivo by sponging miR-338-3p and regulating LIN28B. Cancer Cell Int 2021; 21:412. [PMID: 34353342 PMCID: PMC8340538 DOI: 10.1186/s12935-021-02110-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 07/22/2021] [Indexed: 02/08/2023] Open
Abstract
Background Circular RNAs (circRNAs) could participate in cis-dichlorodiammineplatinum (DDP) resistance of human cancers. However, circRNAs role in DDP resistance of oral squamous cell carcinoma (OSCC) progression remains largely undeveloped. Here, we attempted to explore the role of circ-SCMH1 (ID hsa_circ_0011946) in acquired DDP resistance. Methods Expression of circ-SCMH1, microRNA (miR)-338-3p and Lin-28 homolog B (LIN28B) was detected by real-time quantitative PCR and western blotting, and their interactions were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay. DDP resistance was assessed by MTT assay, colony formation assay, flow cytometry, transwell assays, western blotting, and xenograft experiment. Transmission electron microscopic analysis, nanoparticle tracking analysis and western blotting confirmed the characterizations of extracellular vesicles (EVs). Results Circ-SCMH1 was upregulated in DDP-resistant OSCC tissues and cells (SCC-15/DDP and CAL-27/DDP). Circ-SCMH1 knockdown suppressed the half-maximal inhibitory concentration of DDP, colony formation, and migration/invasion in SCC-15/DDP and CAL-27/DDP cells, but promoted apoptosis rate and apoptotic proteins (Bax and cleaved-caspase-3) expression. However, silencing miR-338-3p abrogated above effects, and overexpressing miR-338-3p mimicked that. Similarly, miR-338-3p overexpression role could be counteracted by restoring LIN28B. Moreover, interfering circ-SCMH1 retarded tumor growth of SCC-15/DDP cells in vivo with DDP treatment or not. Mechanistically, circ-SCMH1 directly sponged miR-338-3p in regulating LIN28B, a target gene for miR-338-3p. Notably, circ-SCMH1 was an EVs cargo, and DDP-resistant OSCC cells-derived EVs could provoke circ-SCMH1 upregulation in parental cells. Conclusion Circ-SCMH1 contributes to chemoresistance of DDP-resistant OSCC cells partially via EVs secretion and circ-SCMH1/miR-338-3p/LIN28B axis. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02110-8.
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Affiliation(s)
- Feng Qiu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Bin Qiao
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Nan Zhang
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China
| | - Zheng Fang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Lu Feng
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Shanfeng Zhang
- Experimental Center for Basic Medicine, Biochemistry and Molecular Biology, Zhengzhou University, Zhengzhou, 450000, Henan, China.
| | - Weiliu Qiu
- Department of Oral and Maxillofacial Surgery, School of Medicine, Ninth People's Hospital, Shanghai Jiao Tong University, No. 639, Manufacturing Bureau Road, Shanghai, 200011, China.
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Zhou HX, Wang LY, Chen S, Wang DD, Fang Z. circ_0005379 inhibits the progression of oral squamous cell carcinoma by regulating the miR-17-5p/acyl-CoA oxidase 1 axis. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2021; 39:425-433. [PMID: 34409798 DOI: 10.7518/hxkq.2021.04.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES To investigate the effects of circ_0005379 on the proliferation, apoptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) cells and its mechanism. METHODS Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of circ_0005379 and miR-17-5p in OSCC tissues and SCC15 cell lines. Western blot was used to detect the expression levels of acyl-CoA oxidase 1 (ACOX1). The circ_0005379 overexpression vector was transfected into SCC15 cells. Methyl thiazolyl tetrazolium blue staining, flow cytometry, Transwell, and Western blot were used to detect the effects of circ_0005379 overexpression on the proliferation, apoptosis, migration, and invasion of SCC15 cells and the expression of E-cadherin, β-catenin, and Snail proteins. Dual luciferase reporter assay and RNA immunoprecipitation were used to examine the regulation of circ_0005379, miR-17-5p, miR-17-5p, and ACOX1 in SCC15 cells. A nude mouse xenograft model of SCC15 cells stably overexpressing circ_0005379 was established, and the effect of circ_0005379 overexpression on the growth of xenografts in nude mice was observed. RESULTS Compared with adjacent cancer tissues, the expression levels of circ_0005379 and ACOX1 proteins in OSCC tissues were decreased (P<0.05), and the expression level of miR-17-5p was increased (P<0.05). Compared with HOK-16A cells, the expression levels of circ_0005379 and ACOX1 proteins in SCC15 cell lines were decreased (P<0.05), and the expression level of miR-17-5p was increased (P<0.05). After overexpressing circ_0005379, the activity and number of migrating and invading SCC15 cells and the expression levels of β-catenin and Snail proteins were decreased (P<0.05); however, the apoptosis rate and expression level of E-cadherin protein were increased (P<0.05). In SCC15 cells, circ_0005379 targeted the negative regulation of miR-17-5p expression, and miR-17-5p targeted the negative regulation of ACOX1 expression. Overexpressing miR-17-5p or silencing ACOX1 could reverse the effects of circ_0005379 overexpression on the proliferation, apoptosis, migration, and invasion of OSCC cell lines. The tumor volume and weight of nude mice overexpressing circ_0005379 were decreased (P<0.05), the expression levels of circ_0005379 and ACOX1 protein in tumor tissues were increased (P<0.05), and the expression level of miR-17-5p was decreased (P<0.05). CONCLUSIONS circ_0005379 may inhibit the proliferation, migration, and invasion of OSCC cells by downregulating the expression of miR-17-5p and upregulating ACOX1, which promote apoptosis and inhibit tumor growth in vivo. circ_0005379 may be a potential target for OSCC treatment.
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Affiliation(s)
- Hai-Xia Zhou
- Center of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Lu-Yao Wang
- Center of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Shuai Chen
- Center of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Dan-Dan Wang
- Center of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zheng Fang
- Center of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Wu Z, He X, Chen S. Oncogenic circDHTKD1 promotes tumor growth and metastasis of oral squamous cell carcinoma in vitro and in vivo via upregulating miR-326-mediated GAB1. ACTA ACUST UNITED AC 2021; 54:e10837. [PMID: 34287578 PMCID: PMC8289343 DOI: 10.1590/1414-431x2020e10837] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 04/27/2021] [Indexed: 01/14/2023]
Abstract
Circular RNAs (circRNAs) have been extensively elucidated with regard to their significant implications in oral squamous cell carcinoma (OSCC). This study performed the functional investigation of circRNA dehydrogenase E1 and transketolase domain containing 1 (circDHTKD1) in OSCC. RNA expression levels of different molecules were measured via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular behaviors were detected by 3-(4, 5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) for cell viability, colony formation assay for clonal capacity, flow cytometry for cell apoptosis, wound healing assay for migration, and transwell assay for migration/invasion. Western blot was used for analyzing protein expression. RNA pull-down and dual-luciferase reporter assays were applied to assess the binding between targets. A xenograft tumor model was established in nude mice for in vivo experiments. Our expression analysis revealed that circDHTKD1 was upregulated in OSCC tissues and cells. circDHTKD1 knockdown was shown to impede OSCC cell growth and metastasis but motivate apoptosis. Additionally, circDHTKD1 served as a microRNA-326 (miR-326) sponge and the function of circDHTKD1 was achieved by sponging miR-326 in OSCC cells. Also, miR-326 inhibited OSCC development via targeting GRB2-associated-binding protein 1 (GAB1). circDHTKD1 could sponge miR-326 to alter GAB1 expression. Furthermore, circDHTKD1 contributed to OSCC progression in vivo via the miR-326/GAB1 axis. These data disclosed a specific circDHTKD1/miR-326/GAB1 signal axis in governing the malignant progression of OSCC, showing the considerable possibility of circDHTKD1 as a predictive and therapeutic target for clinical diagnosis and treatment of OSCC.
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Affiliation(s)
- Zhuangzhi Wu
- Department of Stomatology, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Xiaoning He
- Department of Stomatology, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Siqi Chen
- Department of Stomatology, The Second Affiliated Hospital of Hainan Medical University, Hainan, China
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Zhi Y, Gao L, Wang B, Ren W, Liang KX, Zhi K. Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs. Front Cell Dev Biol 2021; 9:686906. [PMID: 34235152 PMCID: PMC8255676 DOI: 10.3389/fcell.2021.686906] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 05/21/2021] [Indexed: 12/17/2022] Open
Abstract
Ferroptosis is a newly identified form of regulated cell death that is associated with iron metabolism and oxidative stress. As a physiological mechanism, ferroptosis selectively removes cancer cells by regulating the expression of vital chemical molecules. Current findings on regulation of ferroptosis have largely focused on the function of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), in mediating ferroptotic cell death, while the sponging effect of circular RNAs (circRNAs) has not been widely studied. In this review, we discuss the molecular regulation of ferroptosis and highlight the value of circRNAs in controlling ferroptosis and carcinogenesis. Herein, we deliberate future role of this emerging form of regulated cell death in cancer therapeutics and predict the progression and prognosis of oncogenesis in future clinical therapy.
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Affiliation(s)
- Yuan Zhi
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.,Xiangya School of Stomatology, Central South University, Changsha, China
| | - Ling Gao
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.,Key Lab of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Baisheng Wang
- Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital and School of Stomatology, Central South University, Changsha, China
| | - Wenhao Ren
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.,Key Lab of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Kristina Xiao Liang
- Neuro-SysMed, Center of Excellence for Clinical Research in Neurological Diseases, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway
| | - Keqian Zhi
- Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.,Key Lab of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China
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Wu J, Hou J, Li C. Circular RNA Circ_0008450 Regulates the Invasion, Migration, and Proliferation of Oral Squamous Carcinoma Human Oral Squamous Cell 3 Cells by Targeting miR-1294. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
To determine the role of the circ_0008450/miR-1294 molecular axis in the proliferation, migration, and invasion of oral squamous cell carcinoma (OSCC) cells, the expression levels of circ_0008450 and miR-1294 in OSCC and neighboring non-cancerous tissues were detected by real-time quantitative
polymerase chain reaction. Human OSCC HSC3 cells were transfected with negative control (NC) small interfering (Si) RNA (Si-NC), Si-circ_0008450, micro RNA (miR)-NC, miR-1294 mimics, anti-miR-1294, anti-Si-circ_0008450, or anti-miR-NC. The activity of HSC3 cells was detected with the CCK-8
assay. The transwell assay was used to assess the invasion and migration of HSC3 cells. The targeted relationship between miR-1294 and CIRc_0008450 was detected with the dualluciferase report assay. Western blot analysis was performed to measure the protein expression levels of matrix metalloproteinase
(MMP)-2, MMP-9, and Ki-67 (also known as MKI67). As compared to neighboring non-cancerous tissues, the expression levels of circ_0008450 in OSCC tissues were significantly increased (P < 0.05), while miR-1294 levels were significantly decreased (P < 0.05). As compared to
the Si-NC group, cell activity was significantly decreased (P < 0.05), the numbers of migrating and invading cells were significantly decreased (P < 0.05), and the protein levels of Ki-67, MMP-2, and MMP-9 were significantly decreased (P < 0.05) in the Si-circ_0008450
group. The results of the double luciferase assay confirmed targeted binding of circ_0008450 to miR-1294. As compared to the miR-NC group, cell activity was significantly decreased (P < 0.05) in the miR-1294 group, as were the numbers of migrating and invading cells (P <
0.05), and the protein levels of Ki-67, MMP-2, and MMP-9 (P < 0.05). As compared to the Si-circ_0008450+anti-miR-NC group, cell activity was significantly increased (P < 0.05) in the Si-circ_0008450+anti-miR-1294 group, as were the numbers of migrating and invading cells
(P < 0.05), and the protein levels (P < 0.05) of Ki-67, MMP-2, and MMP-9. Interference with circ_0008450 reduced the invasion, migration, and proliferation of OSCC cells on account of upregulation via binding with miR-1294.
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Affiliation(s)
- Jiangen Wu
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China
| | - Jun Hou
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China
| | - Chengjing Li
- Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230061, Anhui, PR China
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Li P, Zhu K, Mo Y, Deng X, Jiang X, Shi L, Guo C, Zhang W, Zeng Z, Li G, Xiong W, Zhang S, Gong Z. Research Progress of circRNAs in Head and Neck Cancers. Front Oncol 2021; 11:616202. [PMID: 33996542 PMCID: PMC8117014 DOI: 10.3389/fonc.2021.616202] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 04/07/2021] [Indexed: 12/13/2022] Open
Abstract
Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Because of their characteristics of a closed loop structure, disease- and tissue-specificity, and high conservation and stability, circRNAs have the potential to be biomarkers for disease diagnosis. Head and neck cancers are one of the most common malignant tumors with high incidence rates globally. Affected patients are often diagnosed at the advanced stage with poor prognosis, owing to the concealment of anatomic sites. The characteristics, functions, and specific mechanisms of circRNAs in head and neck cancers are increasingly being discovered, and they have important clinical significance for the early diagnosis, treatment, and prognosis evaluation of patients with cancer. In this study, the generation, characteristics, and functions of circRNAs, along with their regulatory mechanisms in head and neck cancers have been summarized. We report that circRNAs interact with molecules such as transcription and growth factors to influence specific pathways involved in tumorigenesis. We conclude that circRNAs have an important role to play in the proliferation, invasion, metastasis, energy and substance metabolism, and treatment resistance in cancers.
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Affiliation(s)
- Panchun Li
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Kunjie Zhu
- Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yongzhen Mo
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Xiangying Deng
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Xianjie Jiang
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Lei Shi
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Can Guo
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Wenling Zhang
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China
| | - Shanshan Zhang
- Department of Stomatology, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China
| | - Zhaojian Gong
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
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Fan X, Wang Y. Circular RNA circSPATA6 Inhibits the Progression of Oral Squamous Cell Carcinoma Cells by Regulating TRAF6 via miR-182. Cancer Manag Res 2021; 13:1817-1829. [PMID: 33654430 PMCID: PMC7910102 DOI: 10.2147/cmar.s292074] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 12/24/2020] [Indexed: 12/16/2022] Open
Abstract
Background Oral squamous cell carcinoma (OSCC) has become a widely concerned social problem. Circular RNA spermatogenesis-associated protein 6 (circSPATA6) exhibited low expression in OSCC tissues, yet the regulatory mechanism of circSPATA6 remains vague. Methods Levels of circSPATA6, linear SPATA6, microRNA-182 (miR-182), and tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Migration, invasion, cell cycle arrest, and apoptosis were assessed by Wound-healing, Matrigel invasion, and Flow cytometry assays. The binding relationship between miR-182 and circSPATA6 or TRAF6 was predicted by circRNA interactome or DIANA TOOL and then proved by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. TRAF6 protein level was measured by Western blot assay. The biological role of circSPATA6 on OSCC tumor growth was analyzed by xenograft tumor model in vivo. Exosomes were isolated and detected by differential centrifugation and a transmission electron microscope. Results CircSPATA6 and TRAF6 were declined, and miR-182 was elevated in OSCC cells. Functionally, circSPATA6 impeded migration and invasion, and facilitated cell cycle arrest and apoptosis of OSCC cells. Mechanistically, circSPATA6 could modulate TRAF6 expression through sponging miR-182. Moreover, circSPATA6 blocked tumor growth in the OSCC mice model. Exosomal circSPATA6 retarded the growth of OSCC cells. Conclusion CircSPATA6 curbed migration and invasion, and expedited cell cycle arrest and apoptosis in OSCC cells partly through regulating the miR-182/TRAF6 axis. These findings hinted at an underlying circRNA-targeted therapy for OSCC.
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Affiliation(s)
- Xinhua Fan
- Department of Stomatology, Inner Mongolia Baotou Steel Hospital, Baotou City, Inner Mongolia, People's Republic of China
| | - Ying Wang
- Department of Stomatology, Inner Mongolia Baotou Steel Hospital, Baotou City, Inner Mongolia, People's Republic of China
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Zhang X, Cheng J, Liu S, Li R. Down-regulating circular RNA_0004674 delays the progression of oral squamous cell carcinoma through microRNA-377-3p/THBS1 axis. Life Sci 2021:119236. [PMID: 33621591 DOI: 10.1016/j.lfs.2021.119236] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 02/05/2021] [Accepted: 02/12/2021] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Circular RNAs (CircRNAs) are of great significance in oral squamous cell carcinoma (OSCC) cell progression. Insufficiently, the performance of Circ_0004674 has not been specified in the disease, which alighted our desire to unmask its actions in OSCC cell progression with microRNA (miR)-377-3p and thrombospondin-1 (THBS1). METHODS OSCC expression chip were collected through GEO database and analyzed. The upstream mechanism of THBS1 was predicted through databases. OSCC cancer tissues and normal tissues were resected, in which Circ_0004674, miR-377-3p and THBS1 expression were examined. The relationship of Circ_0004674, miR-377-3p and THBS1 was identified. Circ_0004674- and/or miR-377-3p-related oligonucleotides were transfected into CAL27 cells for detecting cell biological behaviors. Tumors in mice were implanted to monitor the tumor-forming ability of cells. RESULTS THBS1 showed high expression in the three OSCC chips, and it was enriched in PI3K-AKT signaling pathway. The upstream mechanism of THBS1 predicted that Circ_0004674 regulated THBS1 through miR-377-3p. Circ_0004674 and THBS1 levels were enhanced while miR-377-3p level was reduced in OSCC. Down-regulating Circ_0004674 restricted the growth of CAL27 cells in vivo and in vitro. Restoring miR-377-3p, the target gene of Circ_0004674, destroyed CAL27 cell progression and tumor growth. miR-377-3p suppression rescued the effects of down-regulated Circ_0004674 on OSCC. THBS1 was negatively mediated by miR-377-3p. CONCLUSION It is clarified that depleting Circ_0004674 mediates miR-377-3p to restrain THBS1, after which OSCC cell progression can be suppressed. It widens the way to control OSCC from a novel perspective.
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Affiliation(s)
- Xue Zhang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
| | - Junying Cheng
- Department of Magnetic resonance, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Sirui Liu
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Rui Li
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Circ-HIPK3 regulates YAP1 expression by sponging miR-381-3p to promote oral squamous cell carcinoma development. J Biosci 2021. [DOI: 10.1007/s12038-021-00142-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Shi D, Li H, Zhang J, Li Y. CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis. Cancer Manag Res 2021; 13:1371-1382. [PMID: 33603482 PMCID: PMC7886390 DOI: 10.2147/cmar.s277096] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 12/10/2020] [Indexed: 12/16/2022] Open
Abstract
Background Aberrant expression of circular RNA (circRNA) is involved in the occurrence and development of multifarious cancers, including oral squamous cell carcinoma (OSCC). However, the biological role of circGDI2 and the action mechanism in OSCC remain largely unclear. Methods The expression levels of circGDI2, miR-454-3p and forkhead box F2 (FOXF2) were examined by quantitative real-time PCR (qRT-PCR) or Western blot. The stability of circGDI2 was confirmed by Ribonuclease R (RNase R) assay. Cell Counting Kit 8 (CCK8) assay, colony formation and transwell assay were used to detect cell proliferation, migration or invasion. Cell apoptosis was tested by flow cytometry. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the interaction between miR-454-3p and circGDI2 or FOXF2. Moreover, xenograft mouse models were constructed to assess tumor growth in vivo. Results CircGDI2 was a stable circRNA and was low expressed in OSCC tissues and cells. CircGDI2 overexpression could effectively inhibit the proliferation, migration, invasion and promote apoptosis in OSCC cells, and suppress OSCC tumor growth in nude mice in vivo. MiR-454-3p could be sponged by circGDI2, and its overexpression could mitigate the suppressive effects of circGDI2 overexpression on OSCC progression. In addition, FOXF2 was a target of miR-454-3p, and miR-454-3p silence could impede the cell growth of OSCC cells by enhancing FOXF2 expression. Meanwhile, circGDI2 positively regulated FOXF2 expression by targeting miR-454-3p. Conclusion CircGDI2 served as a repressor to restrain OSCC malignancy via miR-454-3p/FOXF2 axis, which might be a novel biomarker for targeted OSCC therapy.
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Affiliation(s)
- Dan Shi
- Department of Oral Medicine Centre, Henan Provincial People's Hospital, Zhengzhou, Henan, People's Republic of China
| | - Huiyun Li
- Department of Anesthesiology, Henan Provincial People's Hospital, Zhengzhou, Henan, People's Republic of China
| | - Junge Zhang
- Department of Ophthalmology, Henan Provincial People's Hospital, Zhengzhou, Henan, People's Republic of China
| | - Yadong Li
- Department of Oral Medicine Centre, Henan Provincial People's Hospital, Zhengzhou, Henan, People's Republic of China
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Zhang Q, Jiang C, Ren W, Li S, Zheng J, Gao Y, Zhi K, Gao L. Circ-LRP6 mediates epithelial-mesenchymal transition and autophagy in oral squamous cell carcinomas. J Oral Pathol Med 2021; 50:660-667. [PMID: 33501755 DOI: 10.1111/jop.13163] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 01/11/2021] [Accepted: 01/14/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND Tumor metastasis seriously affects the therapeutic effect and prognosis of cancer patients. Here, we studied the role of has_circ_0000378 (circ-LRP6) in oral squamous cell carcinoma (OSCC) metastasis to explore new ideas and schemes for clinical treatment. METHODS The expressions of circ-LRP6 in OSCC and normal tissues from matched controls were measured by real-time PCR (RT-PCR). Levels of epithelial-mesenchymal transition (EMT) transcription factors, P62 and LC3B, were determined by Western blot analysis and immunofluorescence (IF) assay. Furthermore, we evaluated the effects of circ-LRP6 downregulation on migration, invasion, and autophagy using CCK8, transwell assays, transmission electron microscopy (TEM), and immunofluorescence (IF) assay. RESULTS The expression of circ-LRP6 in OSCC tissues was high. Downregulation of circ-LRP6 reduced the EMT process of SCC-15 cells, as evidenced by increased E-cadherin and decreased vimentin and Zeb1 levels. Downregulation of circ-LRP6 also decreased autophagy as shown by increased levels of P62 and decreased LC3B in SCC-15 cells. Autophagy revulsant rapamycin (RAPA) rescued the inhibitory effect of circ-LRP6 on LC3B, vimentin, and Zeb1. CONCLUSIONS circ-LRP6 promoted EMT and autophagy of OSCC and increased autophagy could rescue EMT in OSCC cells inhibited by circ-LRP6 siRNA.
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Affiliation(s)
- Qian Zhang
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.,School of Stomatology of Qingdao University, Qingdao, China
| | - Chunmiao Jiang
- School of Stomatology of Qingdao University, Qingdao, China.,Department of Orthodontics, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Wenhao Ren
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shaoming Li
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jingjing Zheng
- Department of Endodontics, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.,Key Lab of Oral Clinical Medicine, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Yuli Gao
- Department of Orthodontics, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Keqian Zhi
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.,Key Lab of Oral Clinical Medicine, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Ling Gao
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.,Key Lab of Oral Clinical Medicine, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
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The Research Progression and Clinical Significance of Circular RNAs in Head and Neck Cancers. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2712310. [PMID: 33150169 PMCID: PMC7603539 DOI: 10.1155/2020/2712310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 09/29/2020] [Accepted: 10/08/2020] [Indexed: 11/17/2022]
Abstract
With rapid development of science technique and molecular research, a large number of circular RNAs (circRNAs) were discovered. CircRNAs that are a heterogeneous endogenous group of non-coding RNA not only are abundantly and diffusely expressed in mammals but also participate in many biological processes, such as in tumor ingenuity and progress. CircRNAs have rarely open reports in the head and neck cancers (HNC), which are an aggressive malignant tumor with unsatisfactory overall survival rates. The diagnostics and treatments continue to improve while the survival rate of HNC patients has no more obvious improvement. Recent studies that are aimed at exploring the molecular mechanisms of occurrence and progression of circRNAs in HNC provide a valuable insight into potential novel diagnostic and therapeutic approaches. In this review, we summarize the increasing number of published researches on the research progression of circRNAs in HNC, as well as their possible clinical implications on HNC.
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Fan HY, Jiang J, Tang YJ, Liang XH, Tang YL. CircRNAs: A New Chapter in Oral Squamous Cell Carcinoma Biology. Onco Targets Ther 2020; 13:9071-9083. [PMID: 32982296 PMCID: PMC7494394 DOI: 10.2147/ott.s263655] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 08/16/2020] [Indexed: 02/05/2023] Open
Abstract
With the rapid development of bioinformatics and gene sequencing technologies, understanding of circular RNAs (circRNAs) has been extended, and numerous studies have identified the key regulator role of circRNAs in a variety of diseases, especially in cancer. Recently, accumulated studies of oral squamous cell carcinoma (OSCC) have discovered the great potential of circRNAs, which can serve as prognostic or diagnostic biomarkers and affect the development and therapy of OSCC. In this review, we detail the new progress of circRNA research for OSCC in order to provide new strategies for clinical diagnosis and treatment.
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Affiliation(s)
- Hua-Yang Fan
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Jian Jiang
- Department of Head and Neck Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China
| | - Ya-Jie Tang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong, People's Republic of China
| | - Xin-Hua Liang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Ya-Ling Tang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
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The Circular RNA-miRNA Axis: A Special RNA Signature Regulatory Transcriptome as a Potential Biomarker for OSCC. MOLECULAR THERAPY. NUCLEIC ACIDS 2020; 22:352-361. [PMID: 33230440 PMCID: PMC7530261 DOI: 10.1016/j.omtn.2020.09.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Oral squamous cell carcinoma (OSCC) is a highly recurrent form of cancer arising from the oral epithelium, which is the result of mutational change due to etiological factors such as tobacco, smoking, chewing of areca nuts, and alcohol consumption. OSCC occurrence has been observed to be prevalent in different regions of Pacific countries and in most Asian countries. Despite the accessibility of the oral cavity, OSCC is diagnosed at an extremely late stage of pathogenic tumor node metastasis pTNM (III–IV), resulting in a poor prognosis for the individual. Therefore, it is important to make definitive, early, and efficient diagnoses. Owing to the development of omic-natured studies, the presence of proteins, transcribed elements, metabolic products, and even microflora detected in saliva helps us to select biomarkers, which is an especially exciting potential because of the availability and the non-invasive nature of sample collection. Since the discovery of circular RNA (circRNA) by Sanger sequencing, it has been reported to play a pivotal role in several human diseases, including cancer. circRNA functions as a microRNA (miRNA) sponge in the regulation of mRNA expression, forming the circRNA-miRNA regulatory axis. In the case of OSCC, overexpression of different circRNAs exhibits both tumor-progressive and tumor-suppressive effects.
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Lin J, Chen L, Chen Q, Zhuang Z, Bao X, Qian J, Hong Y, Yan L, Lin L, Shi B, Qiu Y, Pan L, Wei L, Zheng X, Wang J, Liu F, He B, Chen F. Prognostic value of preoperative systemic inflammation response index in patients with oral squamous cell carcinoma: Propensity score-based analysis. Head Neck 2020; 42:3263-3274. [PMID: 32681711 DOI: 10.1002/hed.26375] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/24/2020] [Accepted: 06/23/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The aim of the study was to elucidate the relationship between systemic inflammation response index (SIRI) and the prognosis of postoperative oral squamous cell carcinoma (OSCC) patients. METHODS The prognostic value of SIRI was evaluated in a prospective cohort consisting of 535 OSCC patients with surgical resection. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses were used to further verify the prognostic value of SIRI. RESULTS Patients with a higher SIRI had a significantly increased risk of mortality compared with those with a low SIRI (HR [hazard ratio]: 1.60, 95% CI [confidence interval]: 1.04-2.47). The similar association pattern was observed following PSM (HR: 1.97, 95% CI: 1.14-3.40) and IPTW (HR: 1.70, 95% CI: 1.29-2.24) analyses. Of note, receiving postoperative chemotherapy resulted in a 72% of decreased risk of death among patients with a higher SIRI (HR: 0.28, 95% CI: 0.08-0.95). Additionally, a novel prognostic nomogram, based on TNM stage, tumor differentiation, and SIRI, demonstrated superior accuracy for the prediction of overall survival than that of the seventh edition of the AJCC staging system. CONCLUSION Preoperative SIRI may be a valuable tool for prediction of survival of OSCC patients.
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Affiliation(s)
- Jing Lin
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Lin Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Qing Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Zhaocheng Zhuang
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Xiaodan Bao
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jiawen Qian
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Yihong Hong
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Lingjun Yan
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Lisong Lin
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Bin Shi
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yu Qiu
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lizhen Pan
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lihong Wei
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xiaoyan Zheng
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jing Wang
- Laboratory Center, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Fengqiong Liu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Baochang He
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Fa Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
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Zhang J, Wang H, Wu K, Zhan F, Zeng H. Dysregulated circRNA_100876 contributes to proliferation and metastasis of colorectal cancer by targeting microRNA-516b (miR-516b). Cancer Biol Ther 2020; 21:733-740. [PMID: 32564659 DOI: 10.1080/15384047.2020.1776075] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer (CRC) is globally one of the most common malignant tumors. Increasing number of studies indicate that circular RNAs (circRNAs) play a significant role in the initiation and progression of CRC. However, the role of circRNA_100876 in CRC progression remains unclear. In this study, we investigated the expression and function of circRNA_100876 in CRC progression. The expression of circRNA_100876 and microRNA-516b (miR-516b) was compared in normal and CRC tissues using quantitative real-time polymerase chain reaction (RT-qPCR). In addition, proliferation, metastasis, and apoptosis of the cells were analyzed using Cell Counting Kit-8 (CCK-8) assay, Transwell assay, and flow cytometry, respectively. The relationship between circRNA_100876 and miR-516b was further verified using dual-luciferase reporter assay. Our data showed that circRNA_100876 was highly expressed in CRC tumor tissues, and the high expression gtransition (EMT)-related proteins. Furthermore, we found that the addition of miR-516b reversed the anti-tumor effect induced by the downregulation of circRNA_100876. In conclusion, this study revealed that circRNA_100876 is overexpressed in CRC tissues and represents a promising therapeutic target for CRC.
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Affiliation(s)
- Jianrong Zhang
- Department of General Surgery, Wuwei People's Hospital , Wuwei, Gansu Province, China
| | - Huaiming Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Gastrointestinal Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, China.,Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong Province, China
| | - Ketong Wu
- Department of Interventional Therapy Center, The Six Affiliated Hospital of Sun-Yat-Sen University , Guangzhou, Guangdong, China
| | - Fajie Zhan
- Department of General Surgery, Wuwei People's Hospital , Wuwei, Gansu Province, China
| | - Huan Zeng
- Department of Medical Laboratory, Wuwei Liangzhou Hospital , Wuwei, Gansu Province, China
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Cristóbal I, Caramés C, Rubio J, Sanz-Alvarez M, Luque M, Madoz-Gúrpide J, Rojo F, García-Foncillas J. Functional and Clinical Impact of CircRNAs in Oral Cancer. Cancers (Basel) 2020; 12:cancers12041041. [PMID: 32340253 PMCID: PMC7226580 DOI: 10.3390/cancers12041041] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/17/2020] [Accepted: 04/17/2020] [Indexed: 12/20/2022] Open
Abstract
The increasing number of recently published works regarding the role of circular RNAs (circRNAs) in oral cancer highlights the key contribution of this novel class of endogenous noncoding RNAs as regulators of critical signaling pathways and their clinical value as novel biomarkers. This review summarizes and puts into context the existing literature in order to clarify the relevance of circRNAs as novel mediators of oral cancer pathogenesis as well as their potential usefulness as predictors of clinical outcome and response to therapy in this disease.
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Affiliation(s)
- Ion Cristóbal
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (C.C.); (J.R.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
- Correspondence: (I.C.); (J.G.-F.); Tel.: +34-915-504-800 (I.C. & J.G.-F.)
| | - Cristina Caramés
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (C.C.); (J.R.)
- Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
| | - Jaime Rubio
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (C.C.); (J.R.)
- Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
| | - Marta Sanz-Alvarez
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.S.-A.); (M.L.); (J.M.-G.); (F.R.)
| | - Melani Luque
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.S.-A.); (M.L.); (J.M.-G.); (F.R.)
| | - Juan Madoz-Gúrpide
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.S.-A.); (M.L.); (J.M.-G.); (F.R.)
| | - Federico Rojo
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.S.-A.); (M.L.); (J.M.-G.); (F.R.)
| | - Jesús García-Foncillas
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.S.-A.); (M.L.); (J.M.-G.); (F.R.)
- Correspondence: (I.C.); (J.G.-F.); Tel.: +34-915-504-800 (I.C. & J.G.-F.)
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Wu J, Chen Z, Song Y, Zhu Y, Dou G, Shen X, Zhou Y, Jiang H, Li J, Peng Y. CircRNA_0005075 suppresses carcinogenesis via regulating miR-431/p53/epithelial-mesenchymal transition axis in gastric cancer. Cell Biochem Funct 2020; 38:932-942. [PMID: 32133664 PMCID: PMC7587004 DOI: 10.1002/cbf.3519] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/06/2020] [Accepted: 02/12/2020] [Indexed: 12/13/2022]
Abstract
This study was aimed to explore the expression and biological function of circRNA_0005075 in gastric cancer (GC) progression and its underlying mechanism. First, the expression level of circRNA_0005075 and microRNA-431 (miR-431) in GC tissues were detected with the quantitative real-time polymerase chain reaction. In addition, after down-regulated the circRNA_0005075 expression by plasmid transfection in GC cells, the Cell Counting Kit-8 (CCK-8), EDU, transwell assay were conducted to evaluate the function of circRNA_0005075 or miR-431 on cell proliferation, metastasis in vitro. Moreover, p53 and Epithelial-mesenchymal transition (EMT) pathway related proteins were also measured with western blotting. Then, our data revealed that CircRNA_0005075 was found to be significantly up-regulated in GC tissues as well as GC cell lines, and the GC patients with higher CircRNA_0005075 expression were more likely to have poor outcomes. Down-regulation of CircRNA_0005075 could significantly suppress the GC cell proliferation and cell metastasis ability, while the addition of miR-431 inhibitors could counteract this effect. Importantly, we discovered that the silencing of circRNA_0005075 could weaken the micro-RNA sponge function for miR-431, and then upregulate the expression of p53 and forbid the EMT signalling pathway, and finally suppress the tumourigenesis of GC. To sum up, CircRNA_0005075 could inhibit cell growth and metastasis of GC through regulating the miR-431/p53/EMT axis. SIGNIFICANCE OF THE STUDY: The research clearly elucidated the potential role and relative regulatory mechanism of circRNA_0005075 in gastric cancer (GC) progression. Briefly, circRNA_0005075 could directly inhibit the expression level of miR-431, then regulate the p53/Epithelial-mesenchymal transition axis, and finally inhibit cell growth and metastasis in GC. Consequently, circRNA_0005075 might act as an oncogene in the GC procession, which provides a promising way for the treatment of GC.
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Affiliation(s)
- Jiaming Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Zhiheng Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Yihuan Song
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Yi Zhu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Guangjian Dou
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Xuning Shen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Yuan Zhou
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Honggang Jiang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Jin Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Yuping Peng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
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circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway. Cell Death Dis 2020; 11:112. [PMID: 32041942 PMCID: PMC7010827 DOI: 10.1038/s41419-020-2273-y] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 01/13/2020] [Accepted: 01/14/2020] [Indexed: 11/08/2022]
Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and has a poor prognosis. Circular RNA (circRNA) has been increasingly recognized as a crucial contributor to carcinogenesis. circRNA_0000140 has been aberrantly expressed in OSCC, but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, actinomycin D, and RNase R treatments were used to confirm head-to-tail junction sequences and the stability of circ_0000140. In vitro cell activities, including proliferation, migration, invasion, and apoptosis, were determined by colony formation, transwell, and flow cytometry assays. The expression levels of circ_0000140, Hippo signaling pathway, and serial epithelial–mesenchymal transition (EMT) markers were measured by quantitative real-time PCR, western blotting, immunofluorescence, and immunohistochemistry. Dual luciferase reporter assays and Argonaute 2-RNA immunoprecipitation assays were performed to explore the interplay among circ_0000140, miR-31, and LATS2. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of OSCC cells. circ_0000140 is derived from exons 7 to 10 of the KIAA0907 gene. It was down-regulated in OSCC tissues and cell lines, and correlated negatively with poor prognostic outcomes in OSCC patients. Gain-of-function experiments demonstrated that circ_0000140 enhancement suppressed cell proliferation, migration, and invasion, and facilitated cell apoptosis in vitro. In xenograft mouse models, overexpression of circ_0000140 was able to repress tumor growth and lung metastasis. Furthermore, mechanistic studies showed that circ_0000140 could bind with miR-31 and up-regulate its target gene LATS2, thus affecting OSCC cellular EMT. Our findings demonstrated the roles of circ_0000140 in OSCC tumorigenesis as well as in metastasis, and circ_0000140 exerts its tumor-suppressing effect through miR-31/LATS2 axis of Hippo signaling pathway in OSCC.
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Wei Z, Lyu B, Hou D, Liu X. Mir-5100 Mediates Proliferation, Migration and Invasion of Oral Squamous Cell Carcinoma Cells Via Targeting SCAI. J INVEST SURG 2019; 34:834-841. [PMID: 31851859 DOI: 10.1080/08941939.2019.1701754] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE We aimed to investigate the role of microRNA-5100 (miRNA-5100) in oral squamous cell carcinoma (OSCC) and its underlying mechanisms.Material/Methods: The expression of miR-5100 and suppressor of cancer cell invasion (SCAI) in OSCC cell lines were examined. A luciferase reporter assay was applied to confirm the combination between miR-5100 and SCAI. Then, miR-5100 inhibitor or small hairpin RNA (shRNA)-SCAI were transfected into cells. Cell Counting Kit-8 assay was executed for testing cell proliferation ability. Flow cytometry assay was exploited for measuring cell cycle. Invasion and migration of OSCC cells were assessed using Transwell assay and wound healing assay. The expression of proteins were detected using western blotting. RESULTS The results demonstrated that the level of miR-5100 was upregulated while SCAI was downregulated in OSCC cells. SCAI was verified as a direct target of miR-5100. MiR-5100 silencing suppressed proliferation of OSCC cells, increased cells in the G1 and G2 phases, and reduced those in the S phase, which was reversed after transfection with shRNA-SCAI. Moreover, miR-5100 inhibitor downregulated the expression of cyclin-dependent kinase-2 (CDK-2) and cyclinD1, accompanied by upregulation in p27 expression, whereas SCAI silencing had the opposite results. The invasion and migration abilities of OSCC cells were reduced after treatment with miR-5100 inhibitor, whereas SCAI silencing suppressed the effects of miR-5100 inhibitor on OSCC cell behaviors. CONCLUSION These findings suggested that miR-5100 silencing inhibit proliferation, invasion and migration of OSCC cells via upregulating the expression of SCAI, which provides theoretical basis and treatment strategies for the treatment of OSCC.
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Affiliation(s)
- Zicheng Wei
- Department of Stomatology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People's Republic of China
| | - Beili Lyu
- Department of Respiration, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People's Republic of China
| | - Deqiang Hou
- Department of Stomatology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People's Republic of China
| | - Xiaoming Liu
- Oral Medicine Center, Institute of Oral Diseases China Academy of Sciences Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China
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