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Lavoro A, Ricci D, Gattuso G, Longo F, Spoto G, Vitale ACV, Giuliana MC, Falzone L, Libra M, Candido S. Recent advances on gene-related DNA methylation in cancer diagnosis, prognosis, and treatment: a clinical perspective. Clin Epigenetics 2025; 17:76. [PMID: 40325471 PMCID: PMC12054201 DOI: 10.1186/s13148-025-01884-2] [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: 01/08/2025] [Accepted: 04/13/2025] [Indexed: 05/07/2025] Open
Abstract
Recent advances in screening programs and the development of innovative therapeutic strategies have significantly improved the clinical outcomes of cancer patients. However, many patients still experience treatment failure, primarily due to inherent or acquired drug resistance mechanisms. This challenge underscores the urgent need for novel therapeutic targets for the effective treatment of malignancies, as well as cancer-specific biomarkers to enhance early diagnosis and guide interventions. Epigenetic mechanisms, including DNA methylation, have recently garnered growing interest as key regulators of gene expression under both physiological and pathological conditions. Although epigenetic dysregulations are reliable tumor hallmarks, DNA methylation is still not routinely integrated into clinical practice, highlighting the need for further research to translate preclinical findings from the bench to the bedside. On these bases, the present review aims to illustrate the state of the art regarding the role of DNA methylation in cancer, describing the technologies currently available for DNA methylation profiling. Furthermore, the latest evidence on the application of DNA methylation hotspots in cancer diagnosis and prognosis, as well as the impact of epidrugs in cancer care, is discussed to provide a comprehensive overview of the potential clinical relevance of DNA methylation in advancing personalized medicine.
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Affiliation(s)
- Alessandro Lavoro
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
| | - Daria Ricci
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
| | - Giuseppe Gattuso
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
| | - Federica Longo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
| | - Graziana Spoto
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
| | | | - Maria Chiara Giuliana
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
| | - Luca Falzone
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.
| | - Massimo Libra
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123, Catania, Italy
| | - Saverio Candido
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123, Catania, Italy
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Moghbeli M. MicroRNAs as the critical regulators of bone metastasis during prostate tumor progression. Int J Biol Macromol 2025; 309:142912. [PMID: 40203904 DOI: 10.1016/j.ijbiomac.2025.142912] [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: 03/01/2025] [Revised: 04/02/2025] [Accepted: 04/05/2025] [Indexed: 04/11/2025]
Abstract
Prostate cancer (PCa) is the most prevalent cancer among men globally. Although, there are various therapeutic methods for the localized or advanced cancers, there is still a high rate of mortality among PCa patients that is mainly associated with bone metastasis in advanced tumors. There are few options available for treating bone metastasis in PCa, which only provide symptom relief without curing the disease. Therefore, it is crucial to evaluate the molecular mechanisms associated with bone metastasis of PCa cells to suggest the novel diagnostic and therapeutic approaches that could lower the morbidity and mortality rates in PCa patients. MicroRNAs (miRNAs) are involved in regulation of various pathophysiological processes such as tumor growth and osteoblasts/osteoclasts formation. Since, miRNA deregulation has been also frequently observed in PCa patients with bone metastasis, we discussed the role of miRNAs in bone metastasis during PCa progression. It has been reported that miRNAs mainly reduced the ability of PCa tumor cells for the bone metastasis through the regulation of WNT, NF-kB, PI3K/AKT, and TGF-β signaling pathways. They also affected the EMT process, transcription factors, and structural proteins to regulate the bone metastasis during PCa progression. This review paves the way to suggest the miRNAs as the reliable markers not only for the non-invasive early diagnosis, but also for the targeted therapy of PCa tumors with bone metastasis.
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Affiliation(s)
- Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Lv J, Chen F, Lv L, Zhang L, Zou H, Liu Y, Bai Y, Fang R, Qin T, Deng Z. LncRNA ABHD11-AS1 Elevates CALM2 to Promote Metastasis of Thyroid Cancer Through Sponging miR-876-5p. Biochem Genet 2025:10.1007/s10528-025-11072-9. [PMID: 40117023 DOI: 10.1007/s10528-025-11072-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/21/2025] [Indexed: 03/23/2025]
Abstract
In the past decade, the treatment of thyroid cancer (TC) has been brought to a new era, but tumor metastasis still is an intractable difficulty in clinical. LncRNA ABHD11-AS1 has been confirmed to be involved in TC progression. However, its specific mechanism remains unknown. Tissues from TC patients and TC cells served as mainly experimental subjects in this study. The migration of TC cells was assessed using the scratch assay, and the ability of cell invasion was evaluated by transwell assay. RT-qPCR and western blot were conducted to determine the levels of related genes and proteins. The dual-luciferase reporter assay was used to validate the relationships among ABHD11-AS1, miR-876-5p and CALM2. ABHD11-AS1 and CALM2 are elevated in TC cancer samples and cells, while the expression of miR-876-5p is reduced. Subsequently, the ability of TC cells to migrate, invade and EMT was inhibited by both ABHD11-AS1 knockdown or miR-876-5p overexpression. Moreover, the suppression of malignant characteristics in TC cells resulting from ABHD11-AS knockdown was counteracted by the inhibition of miR-876-5p or the upregulation of CALM2. On the mechanism, ABHD11-AS1 elevated CALM2 and promoted the malignant development of TC cells by acting as a miR-876-5p sponge. ABHD11-AS1 mediated the miR-876-5p/CALM2 axis to drive the metastasis of thyroid cancer.
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Affiliation(s)
- Juan Lv
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Fukun Chen
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Ling Lv
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Lu Zhang
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Huangren Zou
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Yanlin Liu
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Yuke Bai
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Ruotong Fang
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Tiantian Qin
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China
| | - Zhiyong Deng
- Department of Nuclear Medicine, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan Province, China.
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Guo Y, Huang Q, Heng Y, Zhou Y, Chen H, Xu C, Wu C, Tao L, Zhou L. Circular RNAs in cancer. MedComm (Beijing) 2025; 6:e70079. [PMID: 39901896 PMCID: PMC11788016 DOI: 10.1002/mco2.70079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 12/23/2024] [Accepted: 01/09/2025] [Indexed: 02/05/2025] Open
Abstract
Circular RNA (circRNA), a subtype of noncoding RNA, has emerged as a significant focus in RNA research due to its distinctive covalently closed loop structure. CircRNAs play pivotal roles in diverse physiological and pathological processes, functioning through mechanisms such as miRNAs or proteins sponging, regulation of splicing and gene expression, and serving as translation templates, particularly in the context of various cancers. The hallmarks of cancer comprise functional capabilities acquired during carcinogenesis and tumor progression, providing a conceptual framework that elucidates the nature of the malignant transformation. Although numerous studies have elucidated the role of circRNAs in the hallmarks of cancers, their functions in the development of chemoradiotherapy resistance remain unexplored and the clinical applications of circRNA-based translational therapeutics are still in their infancy. This review provides a comprehensive overview of circRNAs, covering their biogenesis, unique characteristics, functions, and turnover mechanisms. We also summarize the involvement of circRNAs in cancer hallmarks and their clinical relevance as biomarkers and therapeutic targets, especially in thyroid cancer (TC). Considering the potential of circRNAs as biomarkers and the fascination of circRNA-based therapeutics, the "Ying-Yang" dynamic regulations of circRNAs in TC warrant vastly dedicated investigations.
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Affiliation(s)
- Yang Guo
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Qiang Huang
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Yu Heng
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Yujuan Zhou
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Hui Chen
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Chengzhi Xu
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Chunping Wu
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Lei Tao
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Liang Zhou
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
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Wei L, Liang Q, Zhou C, Liu R, Liu Y. PTEN inhibits epithelial mesenchymal transition of thyroid cancer cells by regulating the Wnt/β-Catenin signaling pathway. Discov Oncol 2024; 15:803. [PMID: 39692895 DOI: 10.1007/s12672-024-01596-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 11/15/2024] [Indexed: 12/19/2024] Open
Abstract
OBJECTIVE The global incidence of thyroid cancer (THCA) has significantly risen in recent years. This study aims to investigate the role and mechanisms of PTEN in epithelial mesenchymal transition (EMT), invasion and migration of THCA cells. METHODS PTEN expression in THCA was analyzed through bioinformatics databases. RT-qPCR and Western blot analyses were performed to quantify PTEN levels in the Nthy-ori 3-1 cell line and three THCA cell types (TPC-1, B-CPAP, FTC-133). TPC-1 cells were transfected with a PTEN overexpression plasmid and treated with the Wnt activator. Cell viability and apoptosis were assessed via CCK-8 and flow cytometry, respectively. The expression levels of E-Cadherin, N-Cadherin, and Vimentin in TPC-1 cells were evaluated using Western blot. The invasive, migratory, and wound-healing abilities of the cells were examined using Transwell and scratch assays. Activation of the Wnt/β-catenin pathway was assessed through Western blot. RESULTS PTEN expression was significantly lower in THCA cells, particularly in TPC-1 cells compared to other cell lines. PTEN overexpression led to decreased viability in TPC-1 cells, increased apoptosis, and a rise in E-Cadherin levels while reducing N-Cadherin and Vimentin levels, thereby inhibiting EMT. Furthermore, PTEN overexpression diminished the invasive, migratory and wound-healing capabilities of TPC-1 cells and suppressed activation of the Wnt/β-catenin pathway. Treatment with the Wnt activator partially counteracted the effects of PTEN overexpression on TPC-1 cells. CONCLUSION PTEN functions to inhibit EMT and the invasive and migratory characteristics of THCA cells by blocking the activation of the Wnt/β-catenin pathway.
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Affiliation(s)
- Li Wei
- Department of Ultrasound, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443000, Hubei, China.
| | - Qianhui Liang
- Department of Oncology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443000, Hubei, China
| | - Chang Zhou
- Department of Ultrasound, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443000, Hubei, China
| | - Rong Liu
- Department of Ultrasound, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443000, Hubei, China
| | - Yun Liu
- Department of Ultrasound, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443000, Hubei, China
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Samsami Y, Akhlaghipour I, Taghehchian N, Palizkaran Yazdi M, Farrokhi S, Rahimi HR, Moghbeli M. MicroRNA-382 as a tumor suppressor during tumor progression. Bioorg Med Chem Lett 2024; 113:129967. [PMID: 39293533 DOI: 10.1016/j.bmcl.2024.129967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/27/2024] [Accepted: 09/13/2024] [Indexed: 09/20/2024]
Abstract
Despite the recent progresses in therapeutic and diagnostic methods, there is still a significantly high rate of mortality among cancer patients. One of the main reasons for the high mortality rate in cancer patients is late diagnosis, which leads to the failure of therapeutic strategies. Therefore, investigation of cancer biology can lead to the introduction of early diagnostic markers in these patients. MicroRNAs (miRNAs) play an important role in regulation of cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, these factors can be considered as the non-invasive tumor markers. Deregulation of miR-382 has been widely reported in different cancers. Therefore, in this review, we investigated the role of miR-382 during tumor development. It has shown that miR-382 has mainly a tumor suppressive, which inhibits the growth of tumor cells through the regulation of signaling pathways, RNA-binding proteins, and transcription factors. Therefore, miR-382 can be suggested as a diagnostic and therapeutic marker in cancer patients.
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Affiliation(s)
- Yalda Samsami
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Iman Akhlaghipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Saba Farrokhi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Reza Rahimi
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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7
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Zhang T, Yuan B, Yu S. The Application of microRNAs in Papillary Thyroid Cancer: A Bibliometric and Visualized Analysis. Int J Gen Med 2024; 17:4681-4699. [PMID: 39429957 PMCID: PMC11490214 DOI: 10.2147/ijgm.s487239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 10/02/2024] [Indexed: 10/22/2024] Open
Abstract
Objective Thyroid cancer is the most common malignant endocrine tumor, with papillary thyroid carcinoma (PTC) being the most prevalent type, accounting for 85% of thyroid cancer cases. Here, we conducted a bibliometric analysis of the literature in the field of microRNAs in PTC research to demonstrate current trends and research hotspots, and present a visual map of past and emerging trends. Methods We searched the Web of Scientific Core Collection (WoSCC) database for publications from 1999 to 2023 centered on this field. Next, we employed visualization tools such as VOSviewer, CiteSpace, and Microsoft Excel 2019 to present co-occurrence and co-citation analyses, trends, hotspots, and visual representations of contributions from authors, institutions, journals, and countries/regions. Results The bibliometric analysis encompassed the period from 1999 to 2023, with 994 papers from 54 countries/regions. The country with the most publications and highest total citations was the People's Republic of China, but the United States held the highest average citation rate. Among the top ten productive institutions, the Ohio State University (Ohio State Univ) was the most prominent contributor to this field. The JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (J Clin Endocrinol Metab) ranked first in terms of citation counts and average citations among the top ten productive journals. In terms of keywords, "circular RNAs", "promotes", and "progression" have become prominent research areas. Conclusion This study elucidates current trends, hotspots, and emerging frontiers in miRNA research within PTC, and provides new insights and guidance for future identification of new PTC biomarkers and clinical trials.
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Affiliation(s)
- Tinghua Zhang
- Department of Clinical Laboratory, the Second People’s Hospital of Huaihua City, Huaihua, Hunan, People’s Republic of China
| | - Bo Yuan
- Department of Clinical Laboratory, Southern University of Science and Technology Hospital, Guangdong, Shenzhen, People’s Republic of China
| | - Shaofu Yu
- Department of Clinical Pharmacy, the Second People’s Hospital of Huaihua, Huaihua, Hunan, People’s Republic of China
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Tolue Ghasaban F, Taghehchian N, Zangouei AS, Keivany MR, Moghbeli M. MicroRNA-135b mainly functions as an oncogene during tumor progression. Pathol Res Pract 2024; 262:155547. [PMID: 39151250 DOI: 10.1016/j.prp.2024.155547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 08/12/2024] [Accepted: 08/14/2024] [Indexed: 08/19/2024]
Abstract
Late diagnosis is considered one of the main reasons of high mortality rate among cancer patients that results in therapeutic failure and tumor relapse. Therefore, it is needed to evaluate the molecular mechanisms associated with tumor progression to introduce efficient markers for the early tumor detection among cancer patients. The remarkable stability of microRNAs (miRNAs) in body fluids makes them potential candidates to use as the non-invasive tumor biomarkers in cancer screening programs. MiR-135b has key roles in prognosis and survival of cancer patients by either stimulating or inhibiting cell proliferation, invasion, and angiogenesis. Therefore, in the present review we assessed the molecular biology of miR-135b during tumor progression to introduce that as a novel tumor marker in cancer patients. It has been reported that miR-135b mainly acts as an oncogene by regulation of transcription factors, signaling pathways, drug response, cellular metabolism, and autophagy. This review paves the way to suggest miR-135b as a tumor marker and therapeutic target in cancer patients following the further clinical trials and animal studies.
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Affiliation(s)
- Faezeh Tolue Ghasaban
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Sadra Zangouei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Keivany
- Department of Radiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Akhlaghipour I, Moghbeli M. MicroRNA-98 as a novel diagnostic marker and therapeutic target in cancer patients. Discov Oncol 2024; 15:385. [PMID: 39210158 PMCID: PMC11362465 DOI: 10.1007/s12672-024-01270-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024] Open
Abstract
The progress of cancer treatment methods in the last decade has significantly reduced mortality rate among these patients. Nevertheless, cancer is still recognized as one of the main causes of human deaths. One of the main reasons for the high death rate in cancer patients is the late diagnosis in the advanced tumor stages. Therefore, it is necessary to investigate the molecular biology of tumor progressions in order to introduce early diagnostic markers. MicroRNAs (miRNAs) have an important role in regulating cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, they are widely used as non-invasive markers in the early tumor diagnosis. Since, deregulation of miR-98 has been reported in a wide range of cancers, we investigated the molecular mechanisms of miR-98 during tumor progression. It has been reported that miR-98 mainly inhibits the tumor growth by the modulation of transcription factors and signaling pathways. Therefore, miR-98 can be introduced as a tumor marker and therapeutic target among cancer patients.
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Affiliation(s)
- Iman Akhlaghipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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10
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Palizkaran Yazdi M, Barjasteh A, Moghbeli M. MicroRNAs as the pivotal regulators of Temozolomide resistance in glioblastoma. Mol Brain 2024; 17:42. [PMID: 38956588 PMCID: PMC11218189 DOI: 10.1186/s13041-024-01113-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/17/2024] [Indexed: 07/04/2024] Open
Abstract
Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol for GBM patients, there is still a poor prognosis in these patients. Temozolomide (TMZ) as a first-line therapeutic agent in GBM can easily cross from the blood-brain barrier to inhibit tumor cell proliferation. However, there is a high rate of TMZ resistance in GBM patients. Since, there are limited therapeutic choices for GBM patients who develop TMZ resistance; it is required to clarify the molecular mechanisms of chemo resistance to introduce the novel therapeutic targets. MicroRNAs (miRNAs) regulate chemo resistance through regulation of drug metabolism, absorption, DNA repair, apoptosis, and cell cycle. In the present review we discussed the role of miRNAs in TMZ response of GBM cells. It has been reported that miRNAs mainly induced TMZ sensitivity by regulation of signaling pathways and autophagy in GBM cells. Therefore, miRNAs can be used as the reliable diagnostic/prognostic markers in GBM patients. They can also be used as the therapeutic targets to improve the TMZ response in GBM cells.
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Affiliation(s)
- Mahsa Palizkaran Yazdi
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhosein Barjasteh
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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11
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Lotfi M, Maharati A, Hamidi AA, Taghehchian N, Moghbeli M. MicroRNA-532 as a probable diagnostic and therapeutic marker in cancer patients. Mutat Res 2024; 829:111874. [PMID: 38986233 DOI: 10.1016/j.mrfmmm.2024.111874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 07/01/2024] [Accepted: 07/05/2024] [Indexed: 07/12/2024]
Abstract
The high mortality rate in cancer patients is always one of the main challenges of the health systems globally. Several factors are involved in the high rate of cancer related mortality, including late diagnosis and drug resistance. Cancer is mainly diagnosed in the advanced stages of tumor progression that causes the failure of therapeutic strategies and increases the death rate in these patients. Therefore, assessment of the molecular mechanisms associated with the occurrence of cancer can be effective to introduce early tumor diagnostic markers. MicroRNAs (miRNAs) as the stable non-coding RNAs in the biological body fluids are involved in regulation of cell proliferation, migration, and apoptosis. MiR-532 deregulation has been reported in different tumor types. Therefore, in the present review we discussed the role of miR-532 during tumor growth. It has been shown that miR-532 has mainly a tumor suppressor role through the regulation of transcription factors, chemokines, and signaling pathways such as NF-kB, MAPK, PI3K/AKT, and WNT. In addition to the independent role of miR-532 in regulation of cellular processes, it also functions as a mediator of lncRNAs and circRNAs. Therefore, miR-532 can be considered as a non-invasive diagnostic/prognostic marker as well as a therapeutic target in cancer patients.
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Affiliation(s)
- Malihe Lotfi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhosein Maharati
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Abbas Hamidi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Maharati A, Moghbeli M. Role of microRNA-505 during tumor progression and metastasis. Pathol Res Pract 2024; 258:155344. [PMID: 38744001 DOI: 10.1016/j.prp.2024.155344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 04/23/2024] [Accepted: 05/09/2024] [Indexed: 05/16/2024]
Abstract
Late diagnosis of cancer in advanced stages due to the lack of screening methods is considered as the main cause of poor prognosis and high mortality rate among these patients. Therefore, it is necessary to investigate the molecular tumor biology in order to introduce biomarkers that can be used in cancer screening programs and early diagnosis. MicroRNAs (miRNAs) have key roles in regulation of the cellular pathophysiological processes. Due to the high stability of miRNAs in body fluids, they are widely used as the non-invasive tumor markers. According to the numerous reports about miR-505 deregulation in a wide range of cancers, we investigated the role of miR-505 during tumor progression. It was shown that miR-505 mainly has the tumor suppressor functions through the regulation of signaling pathways, chromatin remodeling, and cellular metabolism. This review has an effective role in introducing miR-505 as a suitable marker for the early cancer diagnosis.
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Affiliation(s)
- Amirhosein Maharati
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Nasimi Shad A, Fanoodi A, Maharati A, Akhlaghipour I, Bina AR, Saburi E, Forouzanfar F, Moghbeli M. Role of microRNAs in tumor progression by regulation of kinesin motor proteins. Int J Biol Macromol 2024; 270:132347. [PMID: 38754673 DOI: 10.1016/j.ijbiomac.2024.132347] [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: 04/02/2024] [Revised: 05/06/2024] [Accepted: 05/11/2024] [Indexed: 05/18/2024]
Abstract
Aberrant cell proliferation is one of the main characteristics of tumor cells that can be affected by many cellular processes and signaling pathways. Kinesin superfamily proteins (KIFs) are motor proteins that are involved in cytoplasmic transportations and chromosomal segregation during cell proliferation. Therefore, regulation of the KIF functions as vital factors in chromosomal stability is necessary to maintain normal cellular homeostasis and proliferation. KIF deregulations have been reported in various cancers. MicroRNAs (miRNAs) and signaling pathways are important regulators of KIF proteins. MiRNAs have key roles in regulation of the cell proliferation, migration, and apoptosis. In the present review, we discussed the role of miRNAs in tumor biology through the regulation of KIF proteins. It has been shown that miRNAs have mainly a tumor suppressor function via the KIF targeting. This review can be an effective step to introduce the miRNAs/KIFs axis as a probable therapeutic target in tumor cells.
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Affiliation(s)
- Arya Nasimi Shad
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Fanoodi
- Student Research Committee, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Amirhosein Maharati
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Iman Akhlaghipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Reza Bina
- Student Research Committee, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Ehsan Saburi
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Forouzanfar
- Clinical Research Development Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Tolue Ghasaban F, Ghanei M, Mahmoudian RA, Taghehchian N, Abbaszadegan MR, Moghbeli M. MicroRNAs as the critical regulators of epithelial mesenchymal transition in pancreatic tumor cells. Heliyon 2024; 10:e30599. [PMID: 38726188 PMCID: PMC11079401 DOI: 10.1016/j.heliyon.2024.e30599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/26/2024] [Accepted: 04/30/2024] [Indexed: 05/12/2024] Open
Abstract
Pancreatic cancer (PC), as one of the main endocrine and digestive systems malignancies has the highest cancer related mortality in the world. Lack of the evident clinical symptoms and appropriate diagnostic markers in the early stages of tumor progression are the main reasons of the high mortality rate among PC patients. Therefore, it is necessary to investigate the molecular pathways involved in the PC progression, in order to introduce novel early diagnostic methods. Epithelial mesenchymal transition (EMT) is a critical cellular process associated with pancreatic tumor cells invasion and distant metastasis. MicroRNAs (miRNAs) are also important regulators of EMT process. In the present review, we discussed the role of miRNAs in regulation of EMT process during PC progression. It has been reported that the miRNAs mainly regulate the EMT process in pancreatic tumor cells through the regulation of EMT-specific transcription factors and several signaling pathways such as WNT, NOTCH, TGF-β, JAK/STAT, and PI3K/AKT. Considering the high stability of miRNAs in body fluids and their role in regulation of EMT process, they can be introduced as the non-invasive diagnostic markers in the early stages of malignant pancreatic tumors. This review paves the way to introduce a non-invasive EMT based panel marker for the early tumor detection among PC patients.
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Affiliation(s)
- Faezeh Tolue Ghasaban
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Ghanei
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reihaneh Alsadat Mahmoudian
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Luo NF, Li JL, Lv J, Chen FK, Li YN, Tang M, Liu PJ. Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway. Heliyon 2024; 10:e27840. [PMID: 38545139 PMCID: PMC10965522 DOI: 10.1016/j.heliyon.2024.e27840] [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: 10/19/2023] [Revised: 03/07/2024] [Accepted: 03/07/2024] [Indexed: 11/11/2024] Open
Abstract
Background In thyroid cancers, a reduction in the expression of the sodium/iodide symporter (NIS) is observed concomitant with a diminution in cancer cell differentiation. The β-catenin/LEF-1 pathway emerges as a crucial regulatory pathway influencing the functional expression of NIS in human thyroid cancer cells. Further research is required to comprehensively elucidate the role of NIS overexpression in impeding the progression of thyroid cancer cells. Methods Human papillary thyroid carcinoma (PTC) cell lines, specifically PTC-1 and KTC-1, were subjected to Scratch and Transwell assays, colony formation, and tumor sphere formation tests to investigate invasion and migration, focusing on the impact of NIS overexpression. The assessment involved the use of western blot to analyze the expression levels of β-catenin, NIS, CD133, SRY-related HMG box2 (Sox2), lymphoid enhancer-binding factor 1 (LEF-1), NANOG, octamer-binding transcription factor 4 (Oct4), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and epithelial cellular adhesion molecule (EpCAM). Statistical analysis was conducted using SPSS version 20.0, and the graphs were developed using GraphPad Prism 7 (GraphPad Software, Inc.). Results Our observations revealed that Nthy-ori-3-1 cell lines exhibited notably higher average expression levels of NIS, yet significantly lower levels of LEF-1 and β-catenin compared to PTC-1 and KTC-1 cell lines. Furthermore, the overexpression of β-catenin resulted in reduced binding of LEF-1 to NIF promotion but concurrently increased the expression of NIS. The downregulation of NIS markedly enhanced the expression of ALDH1A1, CD133, OCT4, Nanog, SOX2, and EpCam-all of which are targets within the Wnt/β-catenin signaling pathway. Conversely, the upregulation of NIS suppressed the expression of these proteins. Moreover, cells treated with β-catenin activators demonstrated an increased capability to form more spheroids and displayed heightened aggressiveness. Conversely, the NIS overexpression (OE) group exhibited suppressed abilities in invasion and colony formation. Conclusion Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the β-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer.
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Affiliation(s)
- Nan-Fang Luo
- Department of Cardiac Function, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China
| | - Jia-Li Li
- Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China
| | - Juan Lv
- Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China
| | - Fu-Kun Chen
- Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China
| | - Ya-Nan Li
- Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China
| | - Ming Tang
- Department of Pathology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China
| | - Peng-Jie Liu
- Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China
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Zheng Q, Lu C, Yu L, Zhan Y, Chen Z. Exploring the metastasis-related biomarker and carcinogenic mechanism in liver cancer based on single cell technology. Heliyon 2024; 10:e27473. [PMID: 38509894 PMCID: PMC10950590 DOI: 10.1016/j.heliyon.2024.e27473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/16/2024] [Accepted: 02/29/2024] [Indexed: 03/22/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a fatal primary malignancy characterized by high invasion and migration. We aimed to explore the underlying metastasis-related mechanism supporting the development of HCC. Methods The dataset of single cell RNA-seq (GSE149614) were collected for cell clustering by using the Seurat R package, the FindAllMarkers function was used to find the highly expression and defined the cell cluster. The WebGestaltR package was used for the GO and KEGG function analysis of shared genes, the Gene Set Enrichment Analysis (GSVA) was performed by clusterProfiler R package, the hTFtarget database was used to identify the crucial transcription factors (TFs), the Genomics of Drug Sensitivity in Cancer (GDSC) database was used for the drug sensitivity analysis. Finally, the overexpression and trans-well assay was used for gene function analysis. Results We obtained 9 cell clusters from the scRNA-seq data, including the nature killer (NK)/T cells, Myeloid cells, Hepatocytes, Epithelial cells, Endothelial cells, Plasma B cells, Smooth muscle cells, B cells, Liver bud hepatic cells. Further cell ecological analysis indicated that the Hepatocytes and Endothelial cell cluster were closely related to the cancer metastasis. Subsequently, the NDUFA4L2-Hepatocyte, GTSE1-Hepatocyte, ENTPD1-Endothelial and NDUFA4L2-Endothelial were defined as metastasis-supporting cell clusters, in which the NDUFA4L2-Hepatocyte cells was closely related to angiogenesis, while the NDUFA4L2-Endothelial was related with the inflammatory response and complement response. The overexpression and trans-well assay displayed that NDUFA4L2 exhibited clearly metastasis-promoting role in HCC progression. Conclusion We identified and defined 4 metastasis-supporting cell clusters by using the single cell technology, the specify shared gene was observed and played crucial role in promoting cancer progression, our findings were expected to provide new insight in control cancer metastasis.
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Affiliation(s)
- Qiuxiang Zheng
- Department of Oncology, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Cuiping Lu
- Department of Oncology, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Lian Yu
- Department of Hematology, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Ying Zhan
- Department of Oncology, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Zhiyong Chen
- Department of Oncology, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, 364000, China
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Sawicka B, Sulewska A, Kulczyńska-Przybik A, Bossowski F, Dulewicz M, Borysewicz-Sańczyk H, Mroczko B, Nikliński J, Bossowski A. Potential Role of Selected miRNAs in the Pathogenesis of Autoimmune Thyroid Diseases in Children and Adolescents. Biomedicines 2024; 12:731. [PMID: 38672087 PMCID: PMC11047951 DOI: 10.3390/biomedicines12040731] [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: 02/13/2024] [Revised: 03/09/2024] [Accepted: 03/20/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Many epigenetic factors, including microRNAs, are involved in the process of changing gene expressions. Small non-coding RNA molecules, called miRNAs, are responsible for regulating gene translation by silencing or degrading target mRNAs. It is acknowledged that for many diseases, they may be novel diagnostic and prognostic biomarkers. Patients with autoimmune thyroid diseases are more likely to develop nodules in the thyroid tissue, and Hashimoto's thyroiditis and Graves' disease predispose patients to thyroid cancer. We evaluated the concentrations of microRNA molecules (miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p, miR-150-5p) in the blood of children with thyroid disorders. In addition, we wished to identify molecules whose change in concentration predisposes to the development of thyroid cancer. AIM The aim of this study is to evaluate selected epigenetic elements by analyzing the levels of miR-15a-5p, miR-126-3p, miR-142-5p, miR-150-5p and miR-21-5p in the blood of pediatric patients with Graves' disease (n = 25), Hashimoto's thyroiditis (n = 26) and thyroid nodular disease (n = 20) compared to a control group of healthy children (n = 17). MATERIALS AND METHODS The study consists of groups of children and adolescents aged 10-18 years with autoimmune thyroid disease, with thyroid nodular disease compared to a control group. The miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p and miR-150-5p molecules were determined through an immunoenzymatic assay using BioVendor reagents. RESULTS There is a statistically significant decrease in the expression of the miR-15a-5p in children with Graves' disease (21.61 vs. 50.22 amol/μL, p = 0.03) and in patients with thyroid nodular disease compared to controls (20.23 vs. 50.22 amol/μL, p = 0.04). Higher levels of the miR-142-5p molecule are found in patients with thyroid disease (with GD-3.8 vs. 3.14 amol/μL, p = 0.01; with HT-3.7 vs. 3.14 amol/μL, p = NS, with thyroid nodular disease-4.16 vs. 3.14 amol/μL, p = 0.04). Lower levels of miR-126-3p were noted in the GD group compared to the control group (7.09 vs. 7.24 amol/μL, p = 0.02). No statistically significant changes in the expressions of miR-150-5p and miR-21-5p molecules were observed in the study groups. CONCLUSIONS 1. The overexpression of the miR-142-5p molecule occurs in children and adolescents with thyroid diseases. 2. Decreased blood levels of miR-15a-5p predispose patients to the formation of focal lesions in the thyroid gland. 3. Identifying a lower expression of the miR-126-3p molecule in the blood of children with GD requires careful follow-up for the development of focal lesions in the thyroid gland and evaluation for their potential malignancy.
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Affiliation(s)
- Beata Sawicka
- Department of Pediatrics, Endocrinology, Diabetology, with Cardiology Divisions, Medical University of Bialystok, 15-089 Bialystok, Poland
| | - Anetta Sulewska
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-089 Bialystok, Poland; (A.S.)
| | | | - Filip Bossowski
- Department of Pediatrics, Endocrinology, Diabetology, with Cardiology Divisions, Medical University of Bialystok, 15-089 Bialystok, Poland
| | - Maciej Dulewicz
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-089 Bialystok, Poland (B.M.)
| | - Hanna Borysewicz-Sańczyk
- Department of Pediatrics, Endocrinology, Diabetology, with Cardiology Divisions, Medical University of Bialystok, 15-089 Bialystok, Poland
| | - Barbara Mroczko
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-089 Bialystok, Poland (B.M.)
| | - Jacek Nikliński
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-089 Bialystok, Poland; (A.S.)
| | - Artur Bossowski
- Department of Pediatrics, Endocrinology, Diabetology, with Cardiology Divisions, Medical University of Bialystok, 15-089 Bialystok, Poland
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Ding W, Chen WW, Wang YQ, Xu XZ, Wang YB, Yan YM, Tan YL. Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells. World J Gastrointest Oncol 2024; 16:458-474. [PMID: 38425400 PMCID: PMC10900153 DOI: 10.4251/wjgo.v16.i2.458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 12/02/2023] [Accepted: 12/20/2023] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal system. ZNF710 is a transcription factor (TF), and zinc finger protein 710 (ZNF710)-AS1-201 is an immune-related long noncoding RNA (lncRNA) that is upregulated in GC cells. AIM To assess the correlation between ZNF710-AS1-201 and immune microenvironment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells. METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital. We assessed cell growth, migration, invasion, and programmed cell death using cell counting kit-8, EdU, scratch, Transwell, and flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify the potential downstream targets of ZNF710-AS1-201. RESULTS In GC tissues with low ZNF710-AS1-201 expression, immunoassays detected significant infiltration of various antitumor immune cells, such as memory CD8 T cells and activated CD4 T cells. In the low-expression group, the half-maximal inhibitory concentrations (IC50s) of 5-fluorouracil, cisplatin, gemcitabine, and trametinib were lower, whereas the IC50s of dasatinib and vorinostat were higher. The malignant degree of GC was higher and the stage was later in the high-expression group. Additionally, patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates. In vitro, the overexpression of ZNF710-AS1-201 greatly enhanced growth, metastasis, and infiltration while suppressing cell death in HGC-27 cells. In contrast, the reduced expression of ZNF710-AS1-201 greatly hindered cell growth, enhanced apoptosis, and suppressed the metastasis and invasion of MKN-45 cells. The expression changes in ZNF710 were significant, but the corresponding changes in isocitrate dehydrogenase-2, Semaphorin 4B, ARHGAP10, RGMB, hsa-miR-93-5p, and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201, as determined by qRT-PCR. CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.
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Affiliation(s)
- Wei Ding
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213003, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213017, Jiangsu Province, China
- Department of General Surgery, The Wujin Clinical College of Xuzhou Medical University, Changzhou 213003, Jiangsu Province, China
| | - Wei-Wei Chen
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213003, Jiangsu Province, China
| | - Yi-Qin Wang
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213003, Jiangsu Province, China
| | - Xue-Zhong Xu
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213003, Jiangsu Province, China
| | - Yi-Bo Wang
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213003, Jiangsu Province, China
| | - Yong-Min Yan
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213017, Jiangsu Province, China
| | - Yu-Lin Tan
- Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213003, Jiangsu Province, China
- Department of General Surgery, The Wujin Clinical College of Xuzhou Medical University, Changzhou 213003, Jiangsu Province, China
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Zhang L, Chen ZY, Wei XX, Li JD, Chen G. What are the changes in the hotspots and frontiers of microRNAs in hepatocellular carcinoma over the past decade? World J Clin Oncol 2024; 15:145-158. [PMID: 38292666 PMCID: PMC10823937 DOI: 10.5306/wjco.v15.i1.145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 12/08/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Emerging research suggests that microRNAs (miRNAs) play an important role in the development of hepatocellular carcinoma (HCC). A comprehensive analysis of recent research concerning miRNAs in HCC development could provide researchers with a valuable reference for further studies. AIM To make a comprehensive analysis of recent studies concerning miRNAs in HCC. METHODS All relevant publications were retrieved from the Web of Science Core Collection database. Bibliometrix software, VOSviewer software and CiteSpace software were used to visually analyze the distribution by time, countries, institutions, journals, and authors, as well as the keywords, burst keywords and thematic map. RESULTS A total of 9426 publications on this topic were found worldwide. According to the keywords analysis, we found that the studies of miRNAs focused on their expression level, effects, and mechanisms on the biological behaviour of HCC. Keywords bursting analysis showed that in the early years (2013-2017), "microRNA expression", "gene expression", "expression profile", "functional polymorphism", "circulating microRNA", "susceptibility" and "mir 21" started to attract attention. In the latest phase (2018-2022), the hot topics turned to "sorafenib resistance", "tumor microenvironment" and so on. CONCLUSION This study provides a comprehensive overview of the role of miRNAs in HCC development based on bibliometric analysis. The hotspots in this field focus on miRNAs expression level, effects, and mechanisms on the biological behavior of HCC. The frontiers turned to sorafenib resistance, tumor microenvironment and so on.
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Affiliation(s)
- Lu Zhang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zu-Yuan Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Xian Wei
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jian-Di Li
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Silaghi H, Pop LA, Georgescu CE, Muntean D, Crișan D, Silaghi P, Lungu I, Nasui BA, Dulf EH, Braicu C, Berindan-Neagoe I, Silaghi CA. MicroRNA Expression Profiling-Potential Molecular Discrimination of Papillary Thyroid Carcinoma Subtypes. Biomedicines 2024; 12:136. [PMID: 38255241 PMCID: PMC10813560 DOI: 10.3390/biomedicines12010136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/28/2023] [Accepted: 01/04/2024] [Indexed: 01/24/2024] Open
Abstract
Recent research has revealed the importance of miRNAs in the diagnosis and clinical evolution of papillary thyroid cancer (PTC). We aim to identify a specific miRNA profile that could differentiate between specific subtypes of PTC. METHODS In this cross-sectional study, total RNA was extracted from paraffin-embedded tissues of 43 patients, 17 with an infiltrative follicular variant of PTC (iFVPTC) and 26 with a conventional variant of PTC (cPTC). Nine miRNAs were evaluated using qRT-PCR technology and specific miRNA assays. RESULTS We found specific patterns for cPTC and iFVPTC, such as miRNA altered in both types of tumours (miR-146b-5p, miR-181a-5p, miR-221-3p, miR-21-5p and miR-222-3p) and two miRNAs significantly expressed only in cPTC (miR-20b-5p, miR-21-5p). The iFVPTC group presented strong and moderate correlations between miRNA expression and clinical data. miR-221-3p, miR-195-5p, miR-181-5p, miR-146b-5p and miR-222 were correlated with age, tumour size (TS) or lymph node metastases (N), while only miR-20b-5p, miR-195-5p and miR-181-5p were correlated with TS, N and age in the cPTC group. CONCLUSIONS The present study allowed the identification of a signature of two miRNAs to confirm miRNA differences between the two histological subtypes of TC. Our results provide advances in the molecular diagnosis of TC and could help to improve the diagnostic performance of already existing molecular classifiers.
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Affiliation(s)
- Horatiu Silaghi
- Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania;
| | - Laura Ancuța Pop
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 400337 Cluj-Napoca, Romania; (C.B.); (I.B.-N.)
| | - Carmen Emanuela Georgescu
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania; (C.E.G.); (C.A.S.)
| | - Diana Muntean
- Department of Pathology, Clinic Municipal Hospital Cluj-Napoca, Tăbăcarilor Street 11, 400139 Cluj-Napoca, Romania;
| | - Doinița Crișan
- Department of Pathology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania;
| | - Patricia Silaghi
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania;
| | - Ionela Lungu
- Cardiomed Medical Center, 17 Republicii Street, 400015 Cluj-Napoca, Romania;
| | - Bogdana Adriana Nasui
- Department of Community Health, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania;
| | - Eva-H. Dulf
- Department of Automation, Faculty of Automation and Computer Science, Technical University of Cluj-Napoca, 28 Memorandumului Street, 400014 Cluj-Napoca, Romania;
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 400337 Cluj-Napoca, Romania; (C.B.); (I.B.-N.)
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 400337 Cluj-Napoca, Romania; (C.B.); (I.B.-N.)
| | - Cristina Alina Silaghi
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania; (C.E.G.); (C.A.S.)
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21
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Maharati A, Tolue Ghasaban F, Akhlaghipour I, Taghehchian N, Zangouei AS, Moghbeli M. MicroRNA-495: a therapeutic and diagnostic tumor marker. J Mol Histol 2023; 54:559-578. [PMID: 37759132 DOI: 10.1007/s10735-023-10159-0] [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: 10/11/2022] [Accepted: 09/18/2023] [Indexed: 09/29/2023]
Abstract
Therapeutic and diagnostic progresses have significantly reduced the mortality rate among cancer patients during the last decade. However, there is still a high rate of mortality among cancer patients. One of the important reasons involved in the high mortality rate is the late diagnosis in advanced tumor stages that causes the failure of therapeutic strategies in these patients. Therefore, investigating the molecular mechanisms involved in tumor progression has an important role in introducing the efficient early detection markers. MicroRNAs (miRNAs) as stable factors in body fluids are always considered as non-invasive diagnostic and prognostic markers. In the present review, we investigated the role of miR-495 in tumor progression. It has been reported that miR-495 has mainly a tumor suppressor function through the regulation of transcription factors and tyrosine kinases as well as cellular processes such as multidrug resistance, chromatin remodeling, and signaling pathways. This review can be an effective step towards introducing the miR-495 as a non-invasive diagnostic/prognostic marker as well as a suitable target in tumor therapy.
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Affiliation(s)
- Amirhosein Maharati
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Faezeh Tolue Ghasaban
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Iman Akhlaghipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Sadra Zangouei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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22
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Wang X, Liu R, Li S, Xia W, Guo H, Yao W, Liang X, Lu Y, Zhang H. The roles, molecular interactions, and therapeutic value of CDK16 in human cancers. Biomed Pharmacother 2023; 164:114929. [PMID: 37236028 DOI: 10.1016/j.biopha.2023.114929] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/15/2023] [Accepted: 05/22/2023] [Indexed: 05/28/2023] Open
Abstract
Cyclin-dependent kinase 16 (CDK16) is an orphan "cyclin-dependent kinase" (CDK) involved in the cell cycle, vesicle trafficking, spindle orientation, skeletal myogenesis, neurite outgrowth, secretory cargo transport, spermatogenesis, glucose transportation, cell apoptosis, cell growth and proliferation, metastasis, and autophagy. Human CDK16 is located on chromosome Xp11.3 and is related to X-linked congenital diseases. CDK16 is commonly expressed in mammalian tissues and may act as an oncoprotein. It is a PCTAIRE kinase in which Cyclin Y or its homologue, Cyclin Y-like 1, regulates activity by binding to the N- and C- terminal regions of CDK16. CDK16 plays a vital role in various cancers, including lung cancer, prostate cancer, breast cancer, malignant melanoma, and hepatocellular carcinoma. CDK16 is a promising biomarker for cancer diagnosis and prognosis. In this review, we summarized and discussed the roles and mechanisms of CDK16 in human cancers.
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Affiliation(s)
- Xiao Wang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Ruiqi Liu
- Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China; Graduate Department, Bengbu Medical College, Bengbu, Anhui, China
| | - Shuang Li
- Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Wenjie Xia
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Haiwei Guo
- Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People' s Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, Zhejiang, China
| | - Weiping Yao
- Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China; Graduate Department, Bengbu Medical College, Bengbu, Anhui, China
| | - Xiaodong Liang
- Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yanwei Lu
- Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
| | - Haibo Zhang
- Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Arriojas A, Patalano S, Macoska J, Zarringhalam K. A Bayesian Noisy Logic Model for Inference of Transcription Factor Activity from Single Cell and Bulk Transcriptomic Data. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.05.03.539308. [PMID: 37205561 PMCID: PMC10187261 DOI: 10.1101/2023.05.03.539308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
The advent of high-throughput sequencing has made it possible to measure the expression of genes at relatively low cost. However, direct measurement of regulatory mechanisms, such as Transcription Factor (TF) activity is still not readily feasible in a high-throughput manner. Consequently, there is a need for computational approaches that can reliably estimate regulator activity from observable gene expression data. In this work, we present a noisy Boolean logic Bayesian model for TF activity inference from differential gene expression data and causal graphs. Our approach provides a flexible framework to incorporate biologically motivated TF-gene regulation logic models. Using simulations and controlled over-expression experiments in cell cultures, we demonstrate that our method can accurately identify TF activity. Moreover, we apply our method to bulk and single cell transcriptomics measurements to investigate transcriptional regulation of fibroblast phenotypic plasticity. Finally, to facilitate usage, we provide user-friendly software packages and a web-interface to query TF activity from user input differential gene expression data: https://umbibio.math.umb.edu/nlbayes/.
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Affiliation(s)
- Argenis Arriojas
- Department of Mathematics, University of Massachusetts Boston, Boston, MA 02125, USA
- Department of Physics, University of Massachusetts Boston, Boston, MA 02125, USA
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Susan Patalano
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Jill Macoska
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Kourosh Zarringhalam
- Department of Mathematics, University of Massachusetts Boston, Boston, MA 02125, USA
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
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24
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Chen Z, Zhong X, Tang W, Xia M, Liu C, Guo Y, Yi Y, Jiang Q, Zu X, Zhong J. Intracellular FGF1 promotes invasion and migration in thyroid carcinoma via HMGA1 independent of FGF receptors. Endocr Connect 2023; 12:e230014. [PMID: 36952626 PMCID: PMC10160558 DOI: 10.1530/ec-23-0014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 03/23/2023] [Indexed: 03/25/2023]
Abstract
Background Fibroblast growth factor 1 (FGF1) is extensively amplified in many tumors and accelerates tumor invasion and metastasis. However, the role and precise molecular mechanism by which FGF1 participates in thyroid cancer (TC) are still unclear. Methods Quantitative real-time polymerase chain reaction- and western blotting were used to detect the mRNA and protein levels of FGF1, high mobility group A (HMGA1), epithelial-to-mesenchymal transition (EMT)-related factors, and FGFs in both TC tissues and cell lines. Immunohistochemistry was conducted to examine the expression of FGF1 and HMGA1. Immunofluorescence staining was used to detect the coexpression of FGF1 and HMGA1. Transwell and wound healing assays were conducted to evaluate the effects of FGF1 on the capacity of invasion and migration in cells. Results FGF1 was upregulated in papillary thyroid carcinoma (PTC) tissues and cell lines and was relatively higher in PTC tissues with cervical lymph node metastasis. Furthermore, FGF1 promotes invasion and metastasis through the EMT pathway. Mechanistically, FGF1 promotes EMT through intracellular function independent of FGF receptors. Interestingly, we demonstrated that FGF1 could upregulate HMGA1 in TC cells, and the correlation of FGF1 and HMGA1 was positive in PTC tissues. FGF1 and HMGA1 had obvious colocalization in the nucleus. We further revealed that FGF1 promotes the invasion and migration of TC cells through the upregulation of HMGA1. Conclusion Intracellular FGF1 could promote invasion and migration in TC by mediating the expression of HMGA1 independent of FGF receptors, and FGF1 may be an effective therapeutic target in TC.
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Affiliation(s)
- Zuyao Chen
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
- The First Affiliated Hospital, Department of Otorhinolaryngology, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Xiaolin Zhong
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
- The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Weiqiang Tang
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Min Xia
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Chang Liu
- Department of Endocrinology and Metabolism, The First People's Hospital of Chenzhou, Chenzhou, China
| | - Yinping Guo
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Yan Yi
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Qingshan Jiang
- The First Affiliated Hospital, Department of Otorhinolaryngology, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Xuyu Zu
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jing Zhong
- The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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25
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Mahmoudian RA, Akhlaghipour I, Lotfi M, Shahidsales S, Moghbeli M. Circular RNAs as the pivotal regulators of epithelial-mesenchymal transition in gastrointestinal tumor cells. Pathol Res Pract 2023; 245:154472. [PMID: 37087995 DOI: 10.1016/j.prp.2023.154472] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 04/11/2023] [Accepted: 04/18/2023] [Indexed: 04/25/2023]
Abstract
Gastrointestinal (GI) cancers, as the most common human malignancies are always considered one of the most important health challenges in the world. Late diagnosis in advanced tumor stages is one of the main reasons for the high mortality rate and treatment failure in these patients. Therefore, investigating the molecular pathways involved in GI tumor progression is required to introduce the efficient markers for the early tumor diagnosis. Epithelial-mesenchymal transition (EMT) is one of the main cellular mechanisms involved in the GI tumor metastasis. Non-coding RNAs (ncRNAs) are one of the main regulatory factors in EMT process. Circular RNAs (circRNAs) are a group of covalently closed loop ncRNAs that have higher stability in body fluids compared with other ncRNAs. Considering the importance of circRNAs in regulation of EMT process, in the present review we discussed the role of circRNAs in EMT process during GI tumor invasion. It has been reported that circRNAs mainly affect the EMT process through the regulation of EMT-specific transcription factors and signaling pathways such as WNT, PI3K/AKT, TGF-β, and MAPK. This review can be an effective step in introducing a circRNA/EMT based diagnostic panel marker for the early tumor detection among GI cancer patients.
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Affiliation(s)
- Reihaneh Alsadat Mahmoudian
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Iman Akhlaghipour
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Malihe Lotfi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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26
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Ruiz-Pozo VA, Cadena-Ullauri S, Guevara-Ramírez P, Paz-Cruz E, Tamayo-Trujillo R, Zambrano AK. Differential microRNA expression for diagnosis and prognosis of papillary thyroid cancer. Front Med (Lausanne) 2023; 10:1139362. [PMID: 37089590 PMCID: PMC10113479 DOI: 10.3389/fmed.2023.1139362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 03/16/2023] [Indexed: 04/08/2023] Open
Abstract
Papillary thyroid cancer accounts for 85% of thyroid cancer. The diagnosis is based on ultrasound methods and tumor biopsies (FNA). In recent years, research has revealed the importance of miRNAs, non-coding RNA molecules that regulate gene expression and are involved in many diseases. The present mini review describes upregulated and downregulated miRNAs expression in papillary thyroid cancer patient samples (tissue, serum, plasma) and the genes regulated by these non-coding molecules. In addition, a bibliographic search was performed to identify the expression of miRNAs that are common in tumor tissue and blood. The miRNAs miR-146b, miR-221-3p, miRNA 222, miR-21, miR-296-5p, and miR-145 are common in both tissue and bloodstream of PTC patient samples. Furthermore, these miRNAs regulate genes involved in biological processes such as cell differentiation, proliferation, migration, invasion, and apoptosis. In conclusion, miRNAs could potentially become valuable biomarkers, which could help in the early diagnosis and prognosis of papillary thyroid cancer.
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Significance of miRNAs on the thyroid cancer progression and resistance to treatment with special attention to the role of cross-talk between signaling pathways. Pathol Res Pract 2023; 243:154371. [PMID: 36791561 DOI: 10.1016/j.prp.2023.154371] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023]
Abstract
Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. It has many types, the Papillary thyroid cancer (PTC)(most common and follicular thyroid carcinoma (FTC). Several risk factors have been associated with TC radiation exposure, autoimmunity, and genetics. Microribonucleic acids (miRNAs) are the most important genetic determinants of TC. They are small chains of nucleic acids that are able to inhibit the expression of several target genes. They could target several genes involved in TC proliferation, angiogenesis, apoptosis, development, and even resistance to therapy. Besides, they could influence the stemness of TC. Moreover, they could regulate several signaling pathways such as WNT/β-catenin, PI3K/AKT/mTOR axis, JAK/STAT, TGF- β, EGFR, and P53. Besides signaling pathways, miRNAs are also involved in the resistance of TC to major treatments such as surgery, thyroid hormone-inhibiting therapy, radioactive iodine, and adjuvant radiation. The stability and sensitivity of several miRNAs might be exploited as an approach for the usage of miRNAs as diagnostic and/or prognostic tools in TC.
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28
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Hamidi AA, Taghehchian N, Zangouei AS, Akhlaghipour I, Maharati A, Basirat Z, Moghbeli M. Molecular mechanisms of microRNA-216a during tumor progression. Cancer Cell Int 2023; 23:19. [PMID: 36740668 PMCID: PMC9899407 DOI: 10.1186/s12935-023-02865-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 02/02/2023] [Indexed: 02/07/2023] Open
Abstract
MicroRNAs (miRNAs) as the members of non-coding RNAs family are involved in post-transcriptional regulation by translational inhibiting or mRNA degradation. They have a critical role in regulation of cell proliferation and migration. MiRNAs aberrations have been reported in various cancers. Considering the importance of these factors in regulation of cellular processes and their high stability in body fluids, these factors can be suggested as suitable non-invasive markers for the cancer diagnosis. MiR-216a deregulation has been frequently reported in different cancers. Therefore, in the present review we discussed the molecular mechanisms of the miR-216a during tumor progression. It has been reported that miR-216a mainly functioned as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review paves the way to suggest the miR-216a as a probable therapeutic and diagnostic target in cancer patients.
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Affiliation(s)
- Amir Abbas Hamidi
- grid.411583.a0000 0001 2198 6209Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- grid.411583.a0000 0001 2198 6209Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Sadra Zangouei
- grid.411583.a0000 0001 2198 6209Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Iman Akhlaghipour
- grid.411583.a0000 0001 2198 6209Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhosein Maharati
- grid.411583.a0000 0001 2198 6209Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Basirat
- grid.411583.a0000 0001 2198 6209Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- grid.411583.a0000 0001 2198 6209Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ,grid.411583.a0000 0001 2198 6209Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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MicroRNA-377: A therapeutic and diagnostic tumor marker. Int J Biol Macromol 2023; 226:1226-1235. [PMID: 36442575 DOI: 10.1016/j.ijbiomac.2022.11.236] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/15/2022] [Accepted: 11/18/2022] [Indexed: 11/26/2022]
Abstract
Cancer is considered as one of the main causes of human deaths globally. Despite the recent progresses in therapeutic modalities, there is still a high rate of mortality among cancer patients. Late diagnosis in advanced tumor stages is one of the main reasons for treatment failure in cancer patients. Therefore, it is required to suggest the novel strategies for the early tumor detection. MicroRNAs (miRNAs) have critical roles in neoplastic transformation by regulation of cell proliferation, migration, and apoptosis. They are always considered as non-invasive markers due to their high stability in body fluids. Since, all of the miRNAs have tissue-specific functions in different tumors as tumor suppressor or oncogene; it is required to investigate the molecular mechanisms of every miRNA in different tumors to introduce that as a suitable non-invasive diagnostic marker in cancer patients. For the first time in the present review, we discussed the role of miR-377 during tumor progression. It has been reported that miR-377 mainly functions as a tumor suppressor through the regulation of signaling pathways and transcription factors. This review is an important step toward introducing the miR-377 as a novel diagnostic marker as well as a therapeutic target in cancer patients.
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30
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Toraih EA, Fawzy MS, Ning B, Zerfaoui M, Errami Y, Ruiz EM, Hussein MH, Haidari M, Bratton M, Tortelote GG, Hilliard S, Nilubol N, Russell JO, Shama MA, El-Dahr SS, Moroz K, Hu T, Kandil E. A miRNA-Based Prognostic Model to Trace Thyroid Cancer Recurrence. Cancers (Basel) 2022; 14:cancers14174128. [PMID: 36077665 PMCID: PMC9454675 DOI: 10.3390/cancers14174128] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/12/2022] [Accepted: 08/21/2022] [Indexed: 12/03/2022] Open
Abstract
Simple Summary Some thyroid tumors elected for surveillance remain indolent, while others progress. The mechanism responsible for this difference is poorly understood, making it challenging to devise patient surveillance plans. Early prediction is important for tailoring treatment and follow-up in high-risk patients. The aim of our study was to identify predictive markers for progression. We leveraged a highly sensitive test that accurately predicts which thyroid nodules are more likely to develop lymph node metastasis, thereby improving care and outcomes for cancer patients. Abstract Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard.
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Affiliation(s)
- Eman A. Toraih
- Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
- Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
- Correspondence: ; Tel.: +1-346-907-4237
| | - Manal S. Fawzy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
- Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar P.O. Box 1321, Saudi Arabia
| | - Bo Ning
- Department of Biochemistry and Molecular Biology, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Mourad Zerfaoui
- Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Youssef Errami
- Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Emmanuelle M. Ruiz
- Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Mohammad H. Hussein
- Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Muhib Haidari
- School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Melyssa Bratton
- Biospecimen Core Laboratory, Louisiana Cancer Research Center, New Orleans, LA 70112, USA
| | - Giovane G. Tortelote
- Section of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Sylvia Hilliard
- Section of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Naris Nilubol
- Endocrine Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20814, USA
| | - Jonathon O. Russell
- Division of Head and Neck Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins, Baltimore, MD 21287, USA
| | - Mohamed A. Shama
- Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Samir S. El-Dahr
- Section of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Krzysztof Moroz
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Tony Hu
- Department of Biochemistry and Molecular Biology, School of Medicine, Tulane University, New Orleans, LA 70112, USA
| | - Emad Kandil
- Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
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