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Gu C, ChenLiu Z, Wu Q, Tang D. ncRNAs as Key Regulators in Gastric Cancer: From Molecular Subtyping to Therapeutic Targets. Ann Surg Oncol 2025:10.1245/s10434-025-17368-9. [PMID: 40358781 DOI: 10.1245/s10434-025-17368-9] [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: 02/20/2025] [Accepted: 04/08/2025] [Indexed: 05/15/2025]
Abstract
Gastric cancer (GC) poses a major global health challenge, underscoring the need for advanced diagnostic and therapeutic approaches. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators in GC, with their dysregulated expression driving key processes such as tumorigenesis, metastasis, immune evasion, and chemoresistance. The functional diversity of ncRNAs across different GC molecular subtypes highlights their potential as biomarkers for improved subtype classification and patient stratification. Beyond their diagnostic value, ncRNAs demonstrate critical regulatory functions in tumor biology, establishing these RNA molecules as promising targets for therapeutic development. Strategies based on RNA hold considerable promise for addressing critical challenges such as immune escape and drug resistance by modulating key signaling pathways. These approaches can enhance immune responses, reprogram the tumor microenvironment, and reverse resistance mechanisms that compromise treatment efficacy, thereby improving clinical outcomes. Although ncRNAs represent a promising frontier in GC precision medicine, further research is required to fully harness their clinical potential.
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Affiliation(s)
- Chen Gu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Zhenni ChenLiu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Qihang Wu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Yangzhou, China.
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Xuzhou Medical University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Dalian Medical University, Dalian Medical University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Nanjing Medical University, Yangzhou, China.
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Han X, Lv C. MiRNA-21 promotes the migration and proliferation of prostate cancer cells via activating the JAK/STAT pathway. Discov Oncol 2025; 16:162. [PMID: 39934499 DOI: 10.1007/s12672-025-01883-y] [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: 10/18/2024] [Accepted: 02/03/2025] [Indexed: 02/13/2025] Open
Abstract
This research explored the role of microRNA (miRNA)-21 in prostate cancer (PCa) cells, as well as its regulation of the JAK/STAT pathway in PCa cells. Quantitative real-time PCR was employed to examine miRNA-21 expression in PCa cells. Cell viability and proliferation were detected by MTT and colony formation assays. Cell migration was measured by wound healing and transwell assays. The janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway-related protein expression was detected using western blot. The results indicated that miRNA-21 was significantly up-regulated in PCa cells, and inhibition of miRNA-21 suppressed the viability, proliferation and migration of PCa cells. Besides, inhibition of miRNA-21 lessened the levels of JAK/STAT pathway-related proteins in both PCa cells. Additionally, Ruxolitinib treatment (an inhibitor of the JAK/STAT pathway) could reverse the elevated cell viability and proliferation in miRNA-21 mimics-transfected PCa cells. Taken together, our study demonstrates that miRNA-21 promotes the migration and proliferation of PCa cells via activating the JAK /STAT pathway.
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Affiliation(s)
- Xin Han
- Pathology Center, Shanghai General Hospital, 85 Wujin Road, Shanghai, 200080, China
| | - Chenjun Lv
- Pathology Center, Shanghai General Hospital, 85 Wujin Road, Shanghai, 200080, China.
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Shargh Z, Asghari K, Asghariehahari M, Chodari L. Combined effect of exercise and curcumin on inflammation-associated microRNAs and cytokines in old male rats: A promising approach against inflammaging. Heliyon 2025; 11:e41895. [PMID: 39897895 PMCID: PMC11782950 DOI: 10.1016/j.heliyon.2025.e41895] [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: 01/19/2024] [Revised: 11/11/2024] [Accepted: 01/09/2025] [Indexed: 02/04/2025] Open
Abstract
Purpose Inflammation serves as a key contributor to various diseases, necessitating the discovery of new treatment approaches to address its causative role. Methods The study involved 35 male Wistar rats, including 7 young rats (3-month-old; 200-250 g) in the Young control group and 28 aged rats (18-month-old; 400-450 g) randomly distributed among the Old control, Exercise, Curcumin, and Exercise + Curcumin groups. During an 8-week period, the Exercise group underwent running on the treadmill (17 m/min), while those in the Curcumin group were supplied with daily curcumin doses (50 mg/kg) through gavage. Upon completion of the study, serum samples from each group were collected for evaluating interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), and Tumor Necrosis Factor-α (TNF-α) levels using ELISA; malondialdehyde (MDA) by enzymatic assay; and miR-21 and miR-146a by RT-PCR. Results Our findings revealed that the Old control group, in contrast to the Young control group, showed a significant reduction in IL-10 serum levels, while MDA, TNF-α, IL-1β, and IL-6 serum levels were significantly elevated. Additionally, the expression of inflammatory microRNAs (miRNAs), miR-21 and miR-146a, was significantly enhanced in the Old control rats compared with the Young control group. Exercise and curcumin treatment alone resulted in an improvement in the expression of the markers and miRNAs associated with inflammation. Furthermore, when exercise and curcumin were administered simultaneously, a synergistic effect was observed compared to the exercise or curcumin alone groups. Conclusion Curcumin and exercise, individually and synergistically in combination, effectively reduced inflammation in aged rats, likely due to decreased oxidative stress and MDA levels mediated by miR-21 and miR-146a downregulation.
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Affiliation(s)
- Zahra Shargh
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Keyvan Asghari
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Morteza Asghariehahari
- Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Leila Chodari
- Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
- Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Ellakwa DES, Abdelmalek MA, Mostafa MM, Ellakwa TE, Wadan AHS. MircoRNAs predict and modulate responses to chemotherapy in leukemic patients. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-024-03675-7. [PMID: 39808312 DOI: 10.1007/s00210-024-03675-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 11/24/2024] [Indexed: 01/16/2025]
Abstract
Leukemia covers a broad category of cancer malignancies that specifically affect bone marrow and blood cells. While different kinds of leukemia have been identified, effective treatments are still lacking for most forms, and even those treatments considered effective can lead to relapses. MicroRNAs, or miRNAs, are short endogenous non-coding single-stranded RNAs that help control the epigenetics of gene expression. Recently, a literature review proposed that miRNAs provided promising therapeutic targets for patients diagnosed with leukemia. Due to genetic abnormalities occurring during the maturation of white blood cells, studies commonly observed uncontrolled replication and decreased cell death, compared to healthy cells. This results in the activation of oncogenes, deactivation of tumor suppressor genes, and disruption of normal cellular functions. Although conventional cancer treatments significantly contribute to patient recovery, they can also impose many side effects. MiRNAs all significantly regulate angiogenesis, migration, apoptosis, carcinogenesis, and gene expression. Regarding chemotherapy, mounting research indicates that microRNAs may directly influence how responsive leukemia is to chemical treatments. This article reviews current studies on microRNAs, examining their influence on cancer advancement and spread, as well as their possible applications as diagnostic indicators and treatment targets in leukemia. Furthermore, we integrated the functions of microRNAs in cancer formation and progression with leukemia patient care, offering fresh insights into leukemia detection and management strategies.
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Affiliation(s)
- Doha El-Sayed Ellakwa
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo, Egypt.
- Department of Biochemistry, Faculty of Pharmacy, Sinai University, Kantra Branch, Ismailia, Egypt.
| | | | - Mostafa M Mostafa
- Department of Molecular and Cellular Physiology, Stritch School of Medicine, Loyola University Chicago, Chicago, USA
| | - Takwa E Ellakwa
- Physical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
| | - Al-Hassan Soliman Wadan
- Oral Biology Department, Faculty of Dentistry, Galala Plateau, Galala University, 15888), Attaka, Suez Governorate, Egypt
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Chen M, Wang T, Tian D, Hai C, Qiu Z. Induction, growth, drug resistance, and metastasis: A comprehensive summary of the relationship between STAT3 and gastric cancer. Heliyon 2024; 10:e37263. [PMID: 39309860 PMCID: PMC11416542 DOI: 10.1016/j.heliyon.2024.e37263] [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: 07/09/2024] [Revised: 08/23/2024] [Accepted: 08/29/2024] [Indexed: 09/25/2024] Open
Abstract
Gastric cancer is a prevalent and highly lethal malignancy that poses substantial challenges to healthcare systems globally. Owing to its often asymptomatic nature in early stages, diagnosis frequently occurs at advanced stages when surgical intervention is no longer a viable option, forcing most patients to rely on nonsurgical treatments such as chemotherapy, targeted therapies, and emerging immunotherapies. Unfortunately, the therapeutic response rates for these treatments are suboptimal, and even among responders, the eventual development of drug resistance remains a significant clinical hurdle. Signal transducer and activator of transcription 3 (STAT3) is a widely expressed cellular protein that plays crucial roles in regulating cellular processes such as growth, metabolism, and immune function. Aberrant activation of the STAT3 pathway has been implicated in the initiation, progression, and therapeutic resistance of several cancers, with gastric cancer being particularly affected. Dysregulated STAT3 signaling not only drives tumorigenesis but also facilitates the development of resistance to chemotherapy and targeted therapies, as well as promotes metastatic dissemination. In this study, we explored the critical role of the STAT3 signaling cascade in the pathogenesis of gastric cancer, its contribution to drug resistance, and its involvement in the metastatic process. Furthermore, we assess recent advances in the development of STAT3 inhibitors and their potential application as therapeutic agents in the treatment of gastric cancer. This work provides a comprehensive overview of the current understanding of STAT3 in gastric cancer and offers a foundation for future research aimed at improving therapeutic outcomes in this challenging disease.
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Affiliation(s)
- Muyang Chen
- School of Pediatrics, Nanjing Medical University, Nanjing, China
| | - Tongshan Wang
- Gastric Cancer Center, Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dianzhe Tian
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chaorui Hai
- School of Life Sciences, Lanzhou University, Lanzhou, China
| | - Zixuan Qiu
- School of Public Health, Xiangya School of Medicine, Central South University, Changsha, China
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Ma Y, Ma Y. Kernel Bayesian logistic tensor decomposition with automatic rank determination for predicting multiple types of miRNA-disease associations. PLoS Comput Biol 2024; 20:e1012287. [PMID: 38976761 PMCID: PMC11257412 DOI: 10.1371/journal.pcbi.1012287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 07/18/2024] [Accepted: 06/27/2024] [Indexed: 07/10/2024] Open
Abstract
Identifying the association and corresponding types of miRNAs and diseases is crucial for studying the molecular mechanisms of disease-related miRNAs. Compared to traditional biological experiments, computational models can not only save time and reduce costs, but also discover potential associations on a large scale. Although some computational models based on tensor decomposition have been proposed, these models usually require manual specification of numerous hyperparameters, leading to a decrease in computational efficiency and generalization ability. Additionally, these linear models struggle to analyze complex, higher-order nonlinear relationships. Based on this, we propose a novel framework, KBLTDARD, to identify potential multiple types of miRNA-disease associations. Firstly, KBLTDARD extracts information from biological networks and high-order association network, and then fuses them to obtain more precise similarities of miRNAs (diseases). Secondly, we combine logistic tensor decomposition and Bayesian methods to achieve automatic hyperparameter search by introducing sparse-induced priors of multiple latent variables, and incorporate auxiliary information to improve prediction capabilities. Finally, an efficient deterministic Bayesian inference algorithm is developed to ensure computational efficiency. Experimental results on two benchmark datasets show that KBLTDARD has better Top-1 precision, Top-1 recall, and Top-1 F1 for new type predictions, and higher AUPR, AUC, and F1 values for new triplet predictions, compared to other state-of-the-art methods. Furthermore, case studies demonstrate the efficiency of KBLTDARD in predicting multiple types of miRNA-disease associations.
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Affiliation(s)
- Yingjun Ma
- School of Mathematics and Statistics, Xiamen University of Technology, Xiamen, China
| | - Yuanyuan Ma
- School of Computer Engineering, Hubei University of Arts and Science, Xiangyang, China
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Liu J, Bao B, Li T, Yang Z, Du Y, Zhang R, Xin J, Hao J, Wang G, Bi H, Guo D. miR-92b-3p protects retinal tissues against DNA damage and apoptosis by targeting BTG2 in experimental myopia. J Transl Med 2024; 22:511. [PMID: 38807184 PMCID: PMC11134754 DOI: 10.1186/s12967-024-05288-3] [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: 07/04/2023] [Accepted: 05/10/2024] [Indexed: 05/30/2024] Open
Abstract
BACKGROUND Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2. METHODS Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting. RESULTS Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia. CONCLUSION In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.
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Affiliation(s)
- Jinpeng Liu
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Bo Bao
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Tuling Li
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Zhaohui Yang
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Yongle Du
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Ruixue Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jizhao Xin
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jiawen Hao
- Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Guimin Wang
- Affiliated Eye Hospital, Shandong University of Traditional Chinese Medicine,No. 48#, Yingxiongshan Road, Jinan, Shandong, 250002, China
| | - Hongsheng Bi
- Affiliated Eye Hospital, Shandong University of Traditional Chinese Medicine,No. 48#, Yingxiongshan Road, Jinan, Shandong, 250002, China.
- Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Experimental Center, Shandong Academy of Eye Disease Prevention and Therapy, Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan, Shandong, 250002, China.
| | - Dadong Guo
- Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Experimental Center, Shandong Academy of Eye Disease Prevention and Therapy, Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan, Shandong, 250002, China.
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Bakinowska E, Kiełbowski K, Skórka P, Dach A, Olejnik-Wojciechowska J, Szwedkowicz A, Pawlik A. Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer-A Narrative Review. Int J Mol Sci 2024; 25:5144. [PMID: 38791187 PMCID: PMC11121563 DOI: 10.3390/ijms25105144] [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: 04/08/2024] [Revised: 05/03/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
Non-coding RNAs (ncRNAs) represent a broad family of molecules that regulate gene expression, including microRNAs, long non-coding RNAs and circular RNAs, amongst others. Dysregulated expression of ncRNAs alters gene expression, which is implicated in the pathogenesis of several malignancies and inflammatory diseases. Gastric cancer is the fifth most frequently diagnosed cancer and the fourth most common cause of cancer-related death. Studies have found that altered expression of ncRNAs may contribute to tumourigenesis through regulating proliferation, apoptosis, drug resistance and metastasis. This review describes the potential use of ncRNAs as diagnostic and prognostic biomarkers. Moreover, we discuss the involvement of ncRNAs in the pathogenesis of gastric cancer, including their interactions with the members of major signalling pathways.
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Affiliation(s)
| | | | | | | | | | | | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (E.B.); (K.K.); (P.S.); (A.D.); (J.O.-W.); (A.S.)
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Meng X, Pang X, Yang J, Zhang X, Dong H. Recent Advances in Electrochemiluminescence Biosensors for MicroRNA Detection. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2307701. [PMID: 38152970 DOI: 10.1002/smll.202307701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 12/06/2023] [Indexed: 12/29/2023]
Abstract
Electrochemiluminescence (ECL) as an analytical technology with a perfect combination of electrochemistry and spectroscopy has received considerable attention in bioanalysis due to its high sensitivity and broad dynamic range. Given the selectivity of bio-recognition elements and the high sensitivity of the ECL analysis technique, ECL biosensors are powerful platforms for the sensitive detection of biomarkers, achieving the accurate prognosis and diagnosis of diseases. MicroRNAs (miRNAs) are crucial biomarkers involved in a variety of physiological and pathological processes, whose aberrant expression is often related to serious diseases, especially cancers. ECL biosensors can fulfill the highly sensitive and selective requirements for accurate miRNA detection, prompting this review. The ECL mechanisms are initially introduced and subsequently categorize the ECL biosensors for miRNA detection in terms of the quenching agents. Furthermore, the work highlights the signal amplification strategies for enhancing ECL signal to improve the sensitivity of miRNA detection and finally concludes by looking at the challenges and opportunities in ECL biosensors for miRNA detection.
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Affiliation(s)
- Xiangdan Meng
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
| | - Xuejiao Pang
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
| | - Junyan Yang
- School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, P. R. China
| | - Xueji Zhang
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
- Marshall Laboratory of Biomedical Engineering, Precision Medicine and Health Research Institute, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518060, P. R. China
| | - Haifeng Dong
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
- Marshall Laboratory of Biomedical Engineering, Precision Medicine and Health Research Institute, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518060, P. R. China
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Yasothkumar D, Ramani P, Jayaraman S, Ramalingam K, Tilakaratne WM. Expression Profile of Circulating Exosomal microRNAs in Leukoplakia, Oral Submucous Fibrosis, and Combined Lesions of Leukoplakia and Oral Submucous Fibrosis. Head Neck Pathol 2024; 18:28. [PMID: 38536520 PMCID: PMC10973321 DOI: 10.1007/s12105-024-01627-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 02/11/2024] [Indexed: 01/11/2025]
Abstract
OBJECTIVES This study aims to elucidate the expression of circulating exosomal miRNAs miRNA 21, miRNA 184, and miRNA 145 in the studied groups, including patients with (i) leukoplakia; (ii) oral submucous fibrosis; (iii) oral submucous fibrosis with leukoplakia; (iv) oral squamous cell carcinoma; and (v) healthy individuals. STUDY DESIGN An observational study was conducted among 54 patients who reported to the outpatient department of Saveetha Dental College and Hospitals. The patients were divided into three groups: Group I healthy individuals (n = 18), Group II: case group (leukoplakia, OSMF, and leukoplakia and OSMF) (n = 18), and Group III: OSCC (n = 18). Real-time polymerase chain reaction analysis was carried out to assess the expression profiles of miRNA 21, miRNA 184, and miRNA 145. The statistical analysis was calculated using SPSS software version 23. RESULTS All three miRNAs showed a statistically significant difference in the one-way ANOVA test between the case group (leukoplakia, OSMF, and leukoplakia and OSMF), healthy group, and OSCC group (p < 0.005). The case group (leukoplakia, OSMF, leukoplakia and OSMF) showed upregulated expression of miRNA 21 and miRNA 184 with threefold change and fourfold change and downregulated expression of miRNA 145 with 1.5-fold change when compared to apparently healthy individuals. CONCLUSION Plasma circulating exosomal miRNAs miRNA 21, miRNA 145, and miRNA 184 expression could be a novel panel of plasma biomarkers to categorise case group (leukoplakia, OSMF, leukoplakia and OSMF) patients with a high risk of malignant transformation.
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Affiliation(s)
- Dinesh Yasothkumar
- Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India.
| | - Pratibha Ramani
- Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Selvaraj Jayaraman
- Department of Biochemistry, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Karthikeyan Ramalingam
- Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - W M Tilakaratne
- Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia
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Chawra HS, Agarwal M, Mishra A, Chandel SS, Singh RP, Dubey G, Kukreti N, Singh M. MicroRNA-21's role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology. Pathol Res Pract 2024; 254:155091. [PMID: 38194804 DOI: 10.1016/j.prp.2024.155091] [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: 12/02/2023] [Revised: 12/31/2023] [Accepted: 01/01/2024] [Indexed: 01/11/2024]
Abstract
MicroRNA-21 (miR-21) was recognized as a key figure in the intricate web of tumor biology, with a prominent role in regulating the PTEN tumor suppressor gene and the PI3K/AKT cascade. This review elucidates the multifaceted interactions between miR-21, PTEN, and the PI3K/AKT signaling, shedding light on their profound implications in cancer initiation, progression, and therapeutic strategies. The core of this review delves into the mechanical intricacies of miR-21-mediated PTEN suppression and its consequent impact on PI3K/AKT pathway activation. It explores how miR-21, as an oncogenic miRNA, targets PTEN directly or indirectly, resulting in uncontrolled activation of PI3K/AKT, fostering cancerous cell survival, proliferation, and evasion of apoptosis. Furthermore, the abstract emphasizes the clinical relevance of these molecular interactions, discussing their implications in various cancer types, prognostic significance, and potential as therapeutic targets. The review provides insights into ongoing research efforts to develop miR-21 inhibitors and strategies to restore PTEN function, offering new avenues for cancer treatment. This article illuminates the critical function of miR-21 in PTEN suppression and PI3K/AKT activation, offering profound insights into its implications for cancer biology and the potential for targeted interventions.
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Affiliation(s)
| | - Mohit Agarwal
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | - Anurag Mishra
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | | | | | - Gaurav Dubey
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | - Neelima Kukreti
- School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India
| | - Mithilesh Singh
- NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India.
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12
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Attachaipanich T, Chattipakorn SC, Chattipakorn N. Current evidence regarding the cellular mechanisms associated with cancer progression due to cardiovascular diseases. J Transl Med 2024; 22:105. [PMID: 38279150 PMCID: PMC10811855 DOI: 10.1186/s12967-023-04803-2] [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: 07/19/2023] [Accepted: 12/13/2023] [Indexed: 01/28/2024] Open
Abstract
Several large cohort studies in cardiovascular disease (CVD) patients have shown an increased incidence of cancer. Previous studies in a myocardial infarction (MI) mouse model reported increased colon, breast, and lung cancer growth. The potential mechanisms could be due to secreted cardiokines and micro-RNAs from pathological hearts and immune cell reprogramming. A study in a MI-induced heart failure (HF) mouse demonstrated an increase in cardiac expression of SerpinA3, resulting in an enhanced proliferation of colon cancer cells. In MI-induced HF mice with lung cancer, the attenuation of tumor sensitivity to ferroptosis via the secretion of miR-22-3p from cardiomyocytes was demonstrated. In MI mice with breast cancer, immune cell reprogramming toward the immunosuppressive state was shown. However, a study in mice with renal cancer reported no impact of MI on tumor growth. In addition to MI, cardiac hypertrophy was shown to promote the growth of breast and lung cancer. The cardiokine potentially involved, periostin, was increased in the cardiac tissue and serum of a cardiac hypertrophy model, and was reported to increase breast cancer cell proliferation. Since the concept that CVD could influence the initiation and progression of several types of cancer is quite new and challenging regarding future therapeutic and preventive strategies, further studies are needed to elucidate the potential underlying mechanisms which will enable more effective risk stratification and development of potential therapeutic interventions to prevent cancer in CVD patients.
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Affiliation(s)
- Tanawat Attachaipanich
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Cardiac Electrophysiology Research Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
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13
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Garg A, Urs AB, Koner BC, Augustine J, Guru SA. Evaluation of Diagnostic Significance of Salivary miRNA-184 and miRNA-21 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders. Head Neck Pathol 2023; 17:961-968. [PMID: 38015343 PMCID: PMC10739647 DOI: 10.1007/s12105-023-01600-7] [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: 09/21/2023] [Accepted: 10/28/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Altered levels of miRNAs might affect the pathogenesis of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). This study evaluated the diagnostic potential of salivary miRNA-21 and miRNA-184 in OSCC and OPMD. METHODS We recruited a total of 90 subjects including OSCC, OPMD, and healthy controls. RNA was isolated from the saliva samples of the study subjects. Expression of miRNA-21 and miRNA-184 was analyzed using qRT-PCR. Their levels were compared and the diagnostic cut-off was determined using the ROC curve. RESULTS There was a significant increase in miRNA-21 and a decrease in miRNA-184 in OSCC and OPMD as compared to healthy controls (p < 0.001). Levels of salivary miRNA-21 and miRNA-184 can differentiate OSCC and OPMD from controls and premalignant conditions from malignant conditions. CONCLUSION Salivary miRNA-21 and miRNA-184 may be beneficial for the early detection of OSCC and OPMD. Also, saliva can be used for detecting neoplastic transformation of oral mucosa since it is non-invasive and easily accessible.
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Affiliation(s)
- Aarushi Garg
- Department of Oral Pathology, Maulana Azad Institute of Dental Sciences, MAMC Complex, Bahadur Shah Zafar Marg, New Delhi, 110002, India
| | - Aadithya B Urs
- Department of Oral Pathology, Maulana Azad Institute of Dental Sciences, MAMC Complex, Bahadur Shah Zafar Marg, New Delhi, 110002, India.
| | - Bidhan Chandra Koner
- Multidisciplinary Research Unit, Maulana Azad Medical College, New Delhi, 110002, India
| | - Jeyaseelan Augustine
- Department of Oral Pathology, Maulana Azad Institute of Dental Sciences, MAMC Complex, Bahadur Shah Zafar Marg, New Delhi, 110002, India
| | - Sameer Ahmad Guru
- Developmental Systems Biology, Ann and Lurie Children's Hospital, Northwestern University, Chicago, Ilinois, 60611, USA
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Liu R, Huang B, Shao Y, Cai Y, Liu X, Ren Z. Identification of memory B-cell-associated miRNA signature to establish a prognostic model in gastric adenocarcinoma. J Transl Med 2023; 21:648. [PMID: 37735667 PMCID: PMC10515266 DOI: 10.1186/s12967-023-04366-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/17/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Memory B cells and microRNAs (miRNAs) play important roles in the progression of gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD). However, few studies have investigated the use of memory B-cell-associated miRNAs in predicting the prognosis of STAD. METHODS We identified the marker genes of memory B cells by single-cell RNA sequencing (scRNA-seq) and identified the miRNAs associated with memory B cells by constructing an mRNA‒miRNA coexpression network. Then, univariate Cox, random survival forest (RSF), and stepwise multiple Cox regression (StepCox) algorithms were used to identify memory B-cell-associated miRNAs that were significantly related to overall survival (OS). A prognostic risk model was constructed and validated using these miRNAs, and patients were divided into a low-risk group and a high-risk group. In addition, the differences in clinicopathological features, tumour microenvironment, immune blocking therapy, and sensitivity to anticancer drugs in the two groups were analysed. RESULTS Four memory B-cell-associated miRNAs (hsa-mir-145, hsa-mir-125b-2, hsa-mir-100, hsa-mir-221) with significant correlations to OS were identified and used to construct a prognostic model. Time-dependent receiver operating characteristic (ROC) curve analysis confirmed the feasibility of the model. Kaplan‒Meier (K‒M) survival curve analysis showed that the prognosis was poor in the high-risk group. Comprehensive analysis showed that patients in the high-risk group had higher immune scores, matrix scores, and immune cell infiltration and a poor immune response. In terms of drug screening, we predicted eight drugs with higher sensitivity in the high-risk group, of which CGP-60474 was associated with the greatest sensitivity. CONCLUSIONS In summary, we identified memory B-cell-associated miRNA prognostic features and constructed a novel risk model for STAD based on scRNA-seq data and bulk RNA-seq data. Among patients in the high-risk group, STAD showed the highest sensitivity to CGP-60474. This study provides prognostic insights into individualized and precise treatment for STAD patients.
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Affiliation(s)
- Ruquan Liu
- School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Guangdong Province Precise Medicine Big Data of Traditional Chinese Medicine Engineering Technology Research Center, Guangzhou, 51006, China
| | - Biaojie Huang
- School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Yongzhao Shao
- Department of Population Health, New York University Grossman School of Medicine, New York, NY, 10016, USA
| | - Yongming Cai
- School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- Guangdong Province Precise Medicine Big Data of Traditional Chinese Medicine Engineering Technology Research Center, Guangzhou, 51006, China
| | - Xi Liu
- School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
| | - Zhonglu Ren
- School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
- Guangdong Province Precise Medicine Big Data of Traditional Chinese Medicine Engineering Technology Research Center, Guangzhou, 51006, China.
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15
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Bilan F, Amini M, Doustvandi MA, Tohidast M, Baghbanzadeh A, Hosseini SS, Mokhtarzadeh A, Baradaran B. Simultaneous suppression of miR-21 and restoration of miR-145 in gastric cancer cells; a promising strategy for inhibition of cell proliferation and migration. BIOIMPACTS : BI 2023; 14:27764. [PMID: 38505672 PMCID: PMC10945301 DOI: 10.34172/bi.2023.27764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 06/13/2023] [Accepted: 06/25/2023] [Indexed: 03/21/2024]
Abstract
Introduction Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. microRNAs are a group of regulatory non-coding RNAs that are involved in GC progression. miR-145 as a tumor suppressor and miR-21 as an oncomiR were shown to be dysregulated in many cancers including GC. This research aimed to enhance the expression of miR-145 while reducing the expression of miR-21 and examine their impact on the proliferation, apoptosis, and migration of GC cells. Methods KATO III cells with high expression levels of miR-21-5p and low expression of miR-145-5p were selected. These cells were then transfected with either miR-145-5p mimics or anti-miR-21-5p, alone or in combination. Afterward, the cell survival rate was determined using the MTT assay, while apoptosis induction was investigated through V-FITC/PI and DAPI staining. Additionally, cell migration was examined using the wound healing assay, and cell cycle progression was analyzed through flow cytometry. Furthermore, gene expression levels were quantified utilizing the qRT-PCR technique. Results The study's findings indicated that the co-replacement of miR-145-5p and anti-miR-21-5p led to a decrease in cell viability and the induction of apoptosis in GC cells. This was achieved via modulating the expression of Bax and Bcl-2, major cell survival regulators. Additionally, the combination therapy significantly increased sub-G1 cell cycle arrest and reduced cell migration by downregulating MMP-9 expression as an epithelial-mesenchymal transition marker. This study provides evidence for the therapeutic possibility of the combination of miR-145-5p and anti-miR-21-5p and also suggests that they could inhibit cell proliferation by modulating the PTEN/AKT1 signaling pathway. Conclusion Our research revealed that utilizing miR-145-5p and anti-miR-21-5p together could be a promising therapeutic approach for treating GC.
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Affiliation(s)
- Farzaneh Bilan
- Department of Biological Science, Faculty of Basic Science, Higher Education Institute of Rab-Rashid, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Maryam Tohidast
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Baghbanzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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16
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Han Y, Shin SH, Lim CG, Heo YH, Choi IY, Kim HH. Synthetic RNA Therapeutics in Cancer. J Pharmacol Exp Ther 2023; 386:212-223. [PMID: 37188531 DOI: 10.1124/jpet.123.001587] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 04/20/2023] [Accepted: 04/27/2023] [Indexed: 05/17/2023] Open
Abstract
Recent advances in the RNA delivery system have facilitated the development of a separate field of RNA therapeutics, with modalities including mRNA, microRNA (miRNA), antisense oligonucleotide (ASO), small interfering RNA, and circular (circRNA) that have been incorporated into oncology research. The main advantages of the RNA-based modalities are high flexibility in designing RNA and rapid production for clinical screening. It is challenging to eliminate tumors by tackling a single target in cancer. In the era of precision medicine, RNA-based therapeutic approaches potentially constitute suitable platforms for targeting heterogeneous tumors that possess multiple sub-clonal cancer cell populations. In this review, we discussed how synthetic coding and non-coding RNAs, such as mRNA, miRNA, ASO, and circRNA, can be applied in the development of therapeutics. SIGNIFICANCE STATEMENT: With development of vaccines against coronavirus, RNA-based therapeutics have received attention. Here, the authors discuss different types of RNA-based therapeutics potentially effective against tumor that are highly heterogeneous giving rise to resistance and relapses to the conventional therapeutics. Moreover, this study summarized recent findings suggesting combination approaches of RNA therapeutics and cancer immunotherapy.
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Affiliation(s)
- Youngjin Han
- Hanmi Research Center, Hanmi Pharmaceutical Co. Ltd., Gyeonggi-do, Republic of Korea (Y.H., S.-H.S., C.G.L., Y.H.H., I.Y.C.); and Biotherapeutics and Glycomics Laboratory, College of Pharmacy (Y.H.H., H.H.K.) and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Republic of Korea (H.H.K.)
| | - Seung-Hyun Shin
- Hanmi Research Center, Hanmi Pharmaceutical Co. Ltd., Gyeonggi-do, Republic of Korea (Y.H., S.-H.S., C.G.L., Y.H.H., I.Y.C.); and Biotherapeutics and Glycomics Laboratory, College of Pharmacy (Y.H.H., H.H.K.) and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Republic of Korea (H.H.K.)
| | - Chang Gyu Lim
- Hanmi Research Center, Hanmi Pharmaceutical Co. Ltd., Gyeonggi-do, Republic of Korea (Y.H., S.-H.S., C.G.L., Y.H.H., I.Y.C.); and Biotherapeutics and Glycomics Laboratory, College of Pharmacy (Y.H.H., H.H.K.) and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Republic of Korea (H.H.K.)
| | - Yong Ho Heo
- Hanmi Research Center, Hanmi Pharmaceutical Co. Ltd., Gyeonggi-do, Republic of Korea (Y.H., S.-H.S., C.G.L., Y.H.H., I.Y.C.); and Biotherapeutics and Glycomics Laboratory, College of Pharmacy (Y.H.H., H.H.K.) and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Republic of Korea (H.H.K.)
| | - In Young Choi
- Hanmi Research Center, Hanmi Pharmaceutical Co. Ltd., Gyeonggi-do, Republic of Korea (Y.H., S.-H.S., C.G.L., Y.H.H., I.Y.C.); and Biotherapeutics and Glycomics Laboratory, College of Pharmacy (Y.H.H., H.H.K.) and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Republic of Korea (H.H.K.)
| | - Ha Hyung Kim
- Hanmi Research Center, Hanmi Pharmaceutical Co. Ltd., Gyeonggi-do, Republic of Korea (Y.H., S.-H.S., C.G.L., Y.H.H., I.Y.C.); and Biotherapeutics and Glycomics Laboratory, College of Pharmacy (Y.H.H., H.H.K.) and Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Republic of Korea (H.H.K.)
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17
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Zhu L, Yuhan J, Yu H, Zhang B, Zhu L, He X, Huang K, Xu W. Aptamer functionalized nucleic acid nano drug for targeted synergistic therapy for colon cancer. J Nanobiotechnology 2023; 21:182. [PMID: 37280622 DOI: 10.1186/s12951-023-01941-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 05/29/2023] [Indexed: 06/08/2023] Open
Abstract
Due to its complicated pathophysiology, propensity for metastasis, and poor prognosis, colon cancer is challenging to treat and must be managed with a combination of therapy. Using rolling circle transcription (RCT), this work created a nanosponge therapeutic medication system (AS1411@antimiR-21@Dox). Using the AS1411 aptamer, this approach accomplished targeted delivery to cancer cells. Furthermore, analysis of cell viability, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) levels revealed that functional nucleic acid nanosponge drug (FND) can kill cancer cells. Moreover, transcriptomics uncovered a putative mechanism for the FND anti-tumor effect. These pathways, which included mitotic metaphase and anaphase as well as the SMAC-mediated dissociation of the IAP: caspase complexes, were principally linked to the cell cycle and cell death. In conclusion, by triggering cell cycle arrest and apoptosis, the nano-synergistic therapeutic system allowed for the intelligent and effective targeted administration of RNA and chemotherapeutic medicines for colon cancer treatment. The system allowed for payload efficiency while being customizable, targeted, reliable, stable, and affordable.
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Affiliation(s)
- Liye Zhu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
- College of Veterinary Medicine, China Agricultural University, Beijing, 100094, China
| | - Jieyu Yuhan
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Hao Yu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Boyang Zhang
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
| | - Longjiao Zhu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China
| | - Xiaoyun He
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Kunlun Huang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Wentao Xu
- Food Laboratory of Zhongyuan, Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, No. 17 Qinghua Donglu, Beijing, 100083, China.
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
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18
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Cao X, Dong J, Sun R, Zhang X, Chen C, Zhu Q. A DNAzyme-enhanced nonlinear hybridization chain reaction for sensitive detection of microRNA. J Biol Chem 2023; 299:104751. [PMID: 37100287 DOI: 10.1016/j.jbc.2023.104751] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/17/2023] [Accepted: 04/20/2023] [Indexed: 04/28/2023] Open
Abstract
As a typical biomarker, the expression of microRNA is closely related to the occurrence of cancer. However, in recent years, the detection methods have had some limitations in the research and application of microRNAs. In this paper, an autocatalytic platform was constructed through the combination of a nonlinear hybridization chain reaction and DNAzyme to achieve efficient detection of microRNA-21. Fluorescently labeled fuel probes can form branched nanostructures and new DNAzyme under the action of the target, and the newly formed DNAzyme can trigger a new round of reactions, resulting in enhanced fluorescence signals. This platform is a simple, efficient, fast, low-cost, and selective method for the detection of microRNA-21, which can detect microRNA-21 at concentrations as low as 0.004 nM and can distinguish sequence differences by single-base differences. In tissue samples from liver cancer patients, the platform shows the same detection accuracy as real-time PCR but with better reproducibility. In addition, through the flexible design of the trigger chain, our method could be adapted to detect other nucleic acids biomarkers.
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Affiliation(s)
- Xiuen Cao
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China
| | - Jiani Dong
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China
| | - Ruowei Sun
- Hunan Zaochen Nanorobot Co. Ltd, Liuyang 410300, Hunan, China
| | - Xun Zhang
- Hunan Zaochen Nanorobot Co. Ltd, Liuyang 410300, Hunan, China
| | - Chuanpin Chen
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China.
| | - Qubo Zhu
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China.
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19
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Jiang C, Feng D, Zhang Y, Yang K, Hu X, Xie Q. SCAT8/miR-125b-5p axis triggers malignant progression of nasopharyngeal carcinoma through SCARB1. BMC Mol Cell Biol 2023; 24:15. [PMID: 37009875 PMCID: PMC10069050 DOI: 10.1186/s12860-023-00477-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 03/20/2023] [Indexed: 04/04/2023] Open
Abstract
Nasopharyngeal carcinoma is a tumor with high malignancy and poor prognosis, which severely affects the health of the patients. LncRNAs and microRNAs are crucial for the occurrence and development of nasopharyngeal carcinoma, which regulate the progression of nasopharyngeal carcinoma through the ceRNA network. SCARB1 plays an essential role in nasopharyngeal carcinoma. However, the mechanism underlying the regulation of SCARB1 in nasopharyngeal carcinoma through non-coding RNAs remains unclear. Our findings indicated that the SCAT8/miR-125b-5p axis promoted the malignant progression of nasopharyngeal carcinoma by driving the expression of SCARB1. Mechanistically, the expression of SCARB1 could be regulated by the lncRNA, SCAT8 and the microRNA, miR-125b-5p. Moreover, as a ceRNA of miR-125b-5p, SCAT8 can not only regulate the expression of SCARB1, but also regulate the malignant progression of nasopharyngeal carcinoma. Notably, our results reveal a novel ceRNA regulatory network in nasopharyngeal carcinoma, which could serve as a potential target for the diagnosis and treatment of nasopharyngeal carcinoma.
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Affiliation(s)
- Chunmao Jiang
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, 400010, China
| | - Dandan Feng
- Department of Otolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University, Chongqing, 400010, China
| | - Yu Zhang
- Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Kun Yang
- Department of Health Management Center, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Xiaotong Hu
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, 400010, China
| | - Qian Xie
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, 400010, China.
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Farasati Far B, Vakili K, Fathi M, Yaghoobpoor S, Bhia M, Naimi-Jamal MR. The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: A review. Life Sci 2023; 316:121340. [PMID: 36586571 DOI: 10.1016/j.lfs.2022.121340] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/16/2022] [Accepted: 12/26/2022] [Indexed: 12/29/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of several target genes. miRNAs play a significant role in cancer biology, as they can downregulate their corresponding target genes by impeding the translation of mRNA (at the mRNA level) as well as degrading mRNAs by binding to the 3'-untranslated (UTR) regions (at the protein level). miRNAs may be employed as cancer biomarkers. Therefore, miRNAs are widely investigated for early detection of cancers which can lead to improved survival rates and quality of life. This is particularly important in the case of gastrointestinal cancers, where early detection of the disease could substantially impact patients' survival. MicroRNA-21 (miR-21 or miRNA-21) is one of the most frequently researched miRNAs, where it is involved in the pathophysiology of cancer and the downregulation of several tumor suppressor genes. In gastrointestinal cancers, miR-21 regulates phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), mothers against decapentaplegic homolog 7 (SMAD7), phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), matrix metalloproteinases (MMPs), β-catenin, tropomyosin 1, maspin, and ras homolog gene family member B (RHOB). In this review, we investigate the functions of miR-21 in pathogenesis and its applications as a diagnostic and prognostic cancer biomarker in four different gastrointestinal cancers, including colorectal cancer (CRC), pancreatic cancer (PC), gastric cancer (GC), and esophageal cancer (EC).
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Affiliation(s)
- Bahareh Farasati Far
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
| | - Kimia Vakili
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Fathi
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shirin Yaghoobpoor
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammed Bhia
- Student Research Committee, Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Reza Naimi-Jamal
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.
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21
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The imminent role of microRNAs in salivary adenoid cystic carcinoma. Transl Oncol 2022; 27:101573. [PMID: 36335706 PMCID: PMC9646983 DOI: 10.1016/j.tranon.2022.101573] [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: 08/22/2022] [Revised: 10/01/2022] [Accepted: 10/18/2022] [Indexed: 11/06/2022] Open
Abstract
Unfortunately, despite the severe problem associated with salivary adenoid cystic carcinoma (SACC), it has not been studied in detail yet. Therefore, the time has come to understand the oncogenic cause of SACC and find the correct molecular markers for diagnosis, prognosis, and therapeutic target to tame this disease. Recently, we and others have suggested that non-coding RNAs, specifically microRNAs and long non-coding RNAs, can be ideal biomarkers for cancer(s) diagnosis and progression. Herein, we have shown that various miRNAs, like miR-155, miR‑103a‑3p, miR-21, and miR-130a increase the oncogenesis process, whereas some miRNAs such as miR-140-5p, miR-150, miR-375, miR-181a, miR-98, miR-125a-5p, miR-582-5p, miR-144-3p, miR-320a, miR-187 and miR-101-3p, miR-143-3p inhibit the salivary adenoid cystic carcinoma progression. Furthermore, we have found that miRNAs also target many vital genes and pathways like mitogen-activated protein kinases-snail family transcriptional repressor 2 (MAPK-Snai2), p38/JNK/ERK, forkhead box C1 protein (FOXC1), mammalian target of rapamycin (mTOR), integrin subunit beta 3 (ITGB3), epidermal growth factor receptor (EGFR)/NF-κB, programmed cell death protein 4 (PDCD4), signal transducer and activator of transcription 3 (STAT3), neuroblastoma RAS (N-RAS), phosphatidylinositol-3-kinase (PI3K)/Akt, MEK/ERK, ubiquitin-like modifier activating enzyme 2 (UBA2), tumor protein D52 (TPD52) which play a crucial role in the regulation of salivary adenoid cystic carcinoma. Therefore, we believe that knowledge from this manuscript will help us find the pathogenesis process in salivary adenoid cystic carcinoma and could also give us better biomarkers of diagnosis and prognosis of the disease.
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22
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Wang S, Gao X, Li J, Wei S, Shao Y, Yin Y, Zhang D, Tang M. The anticancer effects of curcumin and clinical research progress on its effects on esophageal cancer. Front Pharmacol 2022; 13:1058070. [PMID: 36386215 PMCID: PMC9650137 DOI: 10.3389/fphar.2022.1058070] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 10/17/2022] [Indexed: 05/14/2025] Open
Abstract
Esophageal cancer (EC) is a common tumor of the gastrointestinal system and a major threat to human health. The etiology and incidence of EC vary depending on the type of pathology. Owing to the unique physiological structure of the esophagus and the poor biological behavior of EC, the treatment modalities available are limited, and the prognosis of patients is relatively poor. Curcumin is a type of natural phytochemical belonging to the class of phenolic compounds. It exerts favorable anticancer effects on various cancers. A growing body of evidence indicates that curcumin suppresses tumor development and progression by inhibiting tumor cell proliferation, invasion, and migration, thus inducing apoptosis, regulating microRNA expression, reversing multidrug resistance, and inducing sensitivity to the therapeutic effect of chemoradiotherapy. Multiple cellular molecules, growth factors, and genes encoding proteins participating in different signaling pathways interact with each other to contribute to the complex and orderly anticancer effect. The efficacy and safety of curcumin have been established in preclinical studies for EC and clinical trials for other cancers. However, the low bioavailability of curcumin limits its clinical application. Therefore, the modification of curcumin analogs, the combination of curcumin with other drugs or therapies, and the use of novel nanocarriers have been widely investigated to improve the clinical effects of curcumin in EC.
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Affiliation(s)
- Shimeng Wang
- Department of Plastic and Reconstructive Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xinliang Gao
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Jialin Li
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Shixiong Wei
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yifeng Shao
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yipeng Yin
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Duo Zhang
- Department of Plastic and Reconstructive Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Mingbo Tang
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
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23
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Wang YC, Lu S, Zhou XJ, Yang L, Liu P, Zhang L, Hu Y, Dong XZ. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis. Open Med (Wars) 2022; 17:930-946. [PMID: 35647303 PMCID: PMC9113083 DOI: 10.1515/med-2022-0486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 04/15/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to verify the biological function of miR-1273h-5p in gastric cancer (GC) and its underlying mechanisms. The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected using microarrays, miR-1273h-5p, and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA, and protein levels were evaluated using polymerase chain reaction and Western blotting methods, cell proliferation, apoptosis, migration, and invasion were determined by CCK-8, flow cytometry, and transwell assay. Compared to tumor-adjacent normal tissue and gastric epithelial mucosa cell line cells, miR-1273h-5p was significantly downregulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant upregulation of CXCL12 was observed when the miR-1273h-5p was downregulated in GC cells. Additionally, miR-1273h-5p significantly reduces tumor volume and weight. Thus, this study suggests that miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3′-untranslational regions, which may be a novel diagnostic and therapeutic target in GC.
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Affiliation(s)
- Yi-Chen Wang
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Song Lu
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.,College of Pharmacy, Zunyi Medical University, Zunyi 563000, China
| | - Xiao-Jiang Zhou
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Li Yang
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.,College of Pharmacy, Zunyi Medical University, Zunyi 563000, China
| | - Ping Liu
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Lan Zhang
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
| | - Yuan Hu
- Department of Pharmacy, Medical Supplier Center, Chinese PLA General Hospital, No. 28 FuXing Road, Haidian District, Beijing 100853, China
| | - Xian-Zhe Dong
- Department of Pharmacy, Xuanwu Hospital of Capital Medical University, 45 Changchun Road, Xicheng District, Beijing 100053, China
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24
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Tian W, Pang X, Luan F. Diagnosis value of miR-181, miR-652, and CA72-4 for gastric cancer. J Clin Lab Anal 2022; 36:e24411. [PMID: 35446997 PMCID: PMC9169223 DOI: 10.1002/jcla.24411] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 12/01/2022] Open
Abstract
PURPOSE To find a useful disease marker for early diagnosis of gastric cancer, we tried to explore the expression of serum miR-181, miR-652, and carbohydrate antigen 72-4 (CA72-4). PATIENTS AND METHODS According to clinical pathologic stages, 112 patients with gastric cancer were divided into early gastric cancer group (n = 60) and advanced gastric cancer group (n = 52), stage I-II (n = 65), and stage III-IV (n = 47). Another 50 cases of gastric benign lesions and 40 healthy controls were also selected. Real-time quantitative PCR together with chemiluminescence were applied to detect expression levels. ROC curve was applied to judge their diagnostic efficiency. Pearson's correlation analysis was put into use to investigate the relevance of three indicators. RESULTS Compared with benign lesions group and control group, significantly higher expression levels were found in patients of gastric cancer (all p < 0.001). Similarly, compared with early gastric cancer group, significantly higher expression levels were found in advanced gastric cancer group (all p < 0.001). The same result was also found in stage III-IV (all p < 0.001). The best cutoff values were 0.93, 2.38, and 16.94 U/ml, respectively. The area under the curve (0.917, 95%CI: 0.856-0.975) of the three combined diagnosis of early gastric cancer was the largest, and its sensitivity and specificity were 92.5% and 86.8%. And miR-181 and miR-652 were positively correlated with CA72-4 (r = 0.772, p < 0.001, r = 0.853, p < 0.001). CONCLUSION Serum miR-181, miR-652, and CA72-4 are closely linked to the occurrence and development of gastric cancer. Combination of three indicators has diagnostic value for early gastric cancer.
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Affiliation(s)
- Wenyan Tian
- Department of GastroenterologyFirst Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
| | - Xueqin Pang
- Department of GastroenterologyFirst Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
| | - Fujuan Luan
- Department of GastroenterologyFirst Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
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25
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LI X, ZHANG X, MA H, LIU Y, CHENG S, WANG H, SUN J. Upregulation of serum exosomal miR-21 was associated with poor prognosis of acute myeloid leukemia patients. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.51621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Xingang LI
- The Third People's Hospital of Zhengzhou, China
| | | | - Hongxia MA
- The Third People's Hospital of Zhengzhou, China
| | - Yang LIU
- The Third People's Hospital of Zhengzhou, China
| | | | - Huili WANG
- The Third People's Hospital of Zhengzhou, China
| | - Jing SUN
- The Third People's Hospital of Zhengzhou, China
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26
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Yue Y, Lin X, Qiu X, Yang L, Wang R. The Molecular Roles and Clinical Implications of Non-Coding RNAs in Gastric Cancer. Front Cell Dev Biol 2021; 9:802745. [PMID: 34966746 PMCID: PMC8711095 DOI: 10.3389/fcell.2021.802745] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 11/29/2021] [Indexed: 01/19/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies in the world. It is also the fifth most common cancer in China. In recent years, a large number of studies have proved that non-coding RNAs (ncRNAs) can regulate cell proliferation, invasion, metastasis, apoptosis, and angiogenesis. NcRNAs also influence the therapeutic resistance of gastric cancer. NcRNAs mainly consist of miRNAs, lncRNAs and circRNAs. In this paper, we summarized ncRNAs as biomarkers and therapeutic targets for gastric cancer, and also reviewed their role in clinical trials and diagnosis. We sum up different ncRNAs and related moleculars and signaling pathway in gastric cancer, like Bcl-2, PTEN, Wnt signaling. In addition, the potential clinical application of ncRNAs in overcoming chemotherapy and radiotherapy resistance in GC in the future were also focused on.
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Affiliation(s)
- Yanping Yue
- Department of Medical Oncology, Affiliated Cancer Hospital, Nantong University, Nantong, China
| | - Xinrong Lin
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xinyue Qiu
- Department of Medical Oncology, Affiliated Cancer Hospital, Nantong University, Nantong, China
| | - Lei Yang
- Department of Medical Oncology, Affiliated Cancer Hospital, Nantong University, Nantong, China
| | - Rui Wang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
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27
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The Novel Phosphatase Domain Mutations Q171R and Y65S Switch PTEN from Tumor Suppressor to Oncogene. Cells 2021; 10:cells10123423. [PMID: 34943931 PMCID: PMC8700245 DOI: 10.3390/cells10123423] [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: 11/15/2021] [Revised: 11/28/2021] [Accepted: 12/02/2021] [Indexed: 11/17/2022] Open
Abstract
Phosphatase and tensin homolog deleted on chromosome 10, or PTEN, is a well-characterized tumor suppressor with both lipid and protein phosphatase activities. PTEN is often downregulated by epigenetic mechanisms such as hypermethylation, which leads to constitutive activation of the PI3K-Akt pathway. Large datasets from next-generation sequencing, however, revealed that mutations in PTEN may not only hamper protein function but may also affect interactions with downstream effectors, leading to variable oncogenic readouts. Here, two novel PTEN mutations, Q171R and Y65S, identified in Filipino colorectal cancer patients, were phenotypically characterized in NIH3T3 and HCT116 cells, alongside the C124S canonical mutant and wild-type controls. The novel mutants increased cellular proliferation, resistance to apoptosis and migratory capacity. They induced gross morphological changes including cytoplasmic shrinkage, increased cellular protrusions and extensive cytoskeletal reorganization. The mutants also induced a modest increase in Akt phosphorylation. Further mechanistic studies will help determine the differential oncogenic potencies of these mutants, and resolve whether the structural constraints imposed by the mutations may have altered associations with downstream effectors.
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28
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Zhang Y, Huang S, Yang G, Zou L, Huang X, Liu S. The Role of miRNAs during Endoplasmic Reticulum Stress Induced Apoptosis in Digestive Cancer. J Cancer 2021; 12:6787-6795. [PMID: 34659567 PMCID: PMC8517994 DOI: 10.7150/jca.62352] [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: 05/05/2021] [Accepted: 09/18/2021] [Indexed: 11/10/2022] Open
Abstract
Digestive cancer is one of the leading causes of cancer mortality in the world. Despite a number of studies being conducted, the exact mechanism for treating digestive cancer has not yet been fully understood. To survive, digestive cancer cells are subjected to various internal and external adverse factors, such as hypoxia, nutritional deficiencies or drug toxicity, resulting in accumulation of misfolded and unfolded protein in endoplasmic reticulum (ER) lumen further leading to ER stress and the unfolded protein response (UPR). During the last years, studies on the relationship between ER stress and microRNAs (miRNAs) has burst on the scene. miRNAs are non-coding RNAs with a length of 21~22nucleotides involved in post-transcriptional regulation of gene expression, which could be regarded as oncomiRs (tumor inducers) and tumor suppressors regulating cancer cell proliferation, invasion, and apoptosis by differently affecting the expression of genes related to cancer cell signaling. Therefore, investigating the interaction between ER stress and miRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we mainly discuss miRNAs focusing on its regulation, role in ER stress induced apoptosis in Digestive cancer, expound the underlying mechanism, thus provides a theoretical foundation for finding new therapeutic targets of digestive cancer.
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Affiliation(s)
- Yujing Zhang
- Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, China.,Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, 410081, China
| | - Shuai Huang
- Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, China.,Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, 410081, China
| | - Gang Yang
- Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, China.,Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, 410081, China
| | - Lianhong Zou
- Hunan Provincial Institute of Emergency Medicine, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, 410015, China
| | - Xin Huang
- Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, China.,Key Laboratory of Protein Chemistry and Developmental Biology of Fish of Ministry of Education, Hunan Normal University, Changsha, 410081, China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, 410015, China
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29
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Mi C, Zhang D, Li Y, Ren M, Ma W, Lu G, He S. miR-4677-3p participates proliferation and metastases of gastric cancer cell via CEMIP-PI3K/AKT signaling pathway. Cell Cycle 2021; 20:1978-1987. [PMID: 34437815 DOI: 10.1080/15384101.2021.1971375] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Gastric cancer is one of the top three leading causes of cancer-related death in the world. Evidence indicated that miR-4677-3p was dysregulated and involved in modulating invasion and migration in multiple types of cancer cells. The aim of this research is to explore the function and mechanism of miR-4677-3p in the development of gastric cancer. In this study, we discovered that miR-4677-3p was down-regulated in gastric cancer tissues and cells. Over-expression of miR-4677-3p suppressed the proliferation, migration and invasion of gastric cancer cells. Furthermore, miR-4677-3p directly bond to CEMIP 3'UTR region and inhibited CEMIP expression. CEMIP promoted cell proliferation, migration and invasion of gastric cancer cells via accelerating PI3K/AKT signaling pathway. siCEMIP or PI3K/AKT signaling inhibitor (Akti-1/2 and LY294002) partly reversed the effects of miR-4677-3p on the cellular growth and metastasis of gastric cancer. In general, miR-4677-3p regulated the development of gastric cancer through CEMIP-PI3K/AKT signaling pathway axis. This study verified the function and molecular mechanism of miR-4677-3p in gastric cancer cells, and may provide a potential diagnosis/prognosis target for patients with gastric cancer.
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Affiliation(s)
- Chen Mi
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi 'An City, Shaanxi Province, China
| | - Dan Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi 'An City, Shaanxi Province, China
| | - Yarui Li
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi 'An City, Shaanxi Province, China
| | - Mudan Ren
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi 'An City, Shaanxi Province, China
| | - Wenhui Ma
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi 'An City, Shaanxi Province, China
| | - Guifang Lu
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi 'An City, Shaanxi Province, China
| | - Shuixiang He
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi 'An City, Shaanxi Province, China
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30
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Fukada M, Matsuhashi N, Takahashi T, Sugito N, Heishima K, Yoshida K, Akao Y. Postoperative changes in plasma miR21-5p as a novel biomarker for colorectal cancer recurrence: A prospective study. Cancer Sci 2021; 112:4270-4280. [PMID: 34270831 PMCID: PMC8486189 DOI: 10.1111/cas.15065] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/03/2021] [Accepted: 07/13/2021] [Indexed: 01/15/2023] Open
Abstract
Cancer‐related microRNAs (miRNAs) are emerging as promising and noninvasive biomarkers for colorectal cancer (CRC). This study aimed to investigate the usefulness of postoperative changes in plasma miR21‐5p levels for recurrence and progressive disease (PD) after surgical resection. This study was a prospective study of 103 CRC patients who underwent surgical resection. Self‐paired plasma samples collected pre‐operation (Pre), 7 days post‐operation (POD7), 1 month post‐operation (POM1), and 6 months post‐operation (POM6) were analyzed. The miRNA levels were evaluated by quantitative reverse transcription PCR. Among the enrolled patients, ten cases (9.7%) of postoperative recurrence and six cases (5.8%) of postoperative PD occurred at POM6. In the recurrence and PD group, plasma miR21‐5p levels significantly increased (POM1: P < .01, POM6: P < .01, respectively). The area under the curve (AUC) value for postoperative changes in plasma miR21‐5p levels at POM1 and POM6 to discriminate recurrence and PD were 0.675 and 0.715, respectively. Combined analysis with postoperative carcinoembryonic antigen (CEA) level in discriminating recurrence and PD increased AUC values (POM1: 0.715 and POM6: 0.789). Furthermore, multivariate analysis for recurrence and PD after surgical resection showed that postoperative changes in the plasma miR21‐5p level at POM1 and POM6 were independent prognostic factors (POM1: P = .03, POM6: P < .01). The postoperative changes in plasma miR21‐5p level could be a useful noninvasive biomarker for monitoring and predicting recurrence and PD after surgical resection of CRC patients. Furthermore, plasma miR21‐5p can predict recurrence and PD after surgical resection.
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Affiliation(s)
- Masahiro Fukada
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Nobuhisa Matsuhashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Takao Takahashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Nobuhiko Sugito
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
| | - Kazuki Heishima
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
| | - Kazuhiro Yoshida
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Yukihiro Akao
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
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31
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Liu X, Ma R, Yi B, Riker AI, Xi Y. MicroRNAs are involved in the development and progression of gastric cancer. Acta Pharmacol Sin 2021; 42:1018-1026. [PMID: 33037405 PMCID: PMC8208993 DOI: 10.1038/s41401-020-00540-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/14/2020] [Indexed: 02/08/2023]
Abstract
MicroRNAs (miRNAs) are recognized as an essential component of the RNA family, exerting multiple and intricate biological functions, particularly in the process of tumorigenesis, proliferation, and metastatic progression. MiRNAs are altered in gastric cancer (GC), showing activity as both tumor suppressors and oncogenes, although their true roles have not been fully understood. This review will focus upon the recent advances of miRNA studies related to the regulatory mechanisms of gastric tumor cell proliferation, apoptosis, and cell cycle. We hope to provide an in-depth insight into the mechanistic role of miRNAs in GC development and progression. In particular, we summarize the latest studies relevant to miRNAs' impact upon the epithelial-mesenchymal transition, tumor microenvironment, and chemoresistance in GC cells. We expect to elucidate the molecular mechanisms involving miRNAs for better understanding the etiology of GC, and facilitating the development of new treatment regimens for the treatment of GC.
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Affiliation(s)
- Xiaolin Liu
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
- Department of Oncology, the First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China
| | - Ruixia Ma
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, 221000, China
| | - Bin Yi
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Adam I Riker
- Geaton and JoAnn DeCesaris Cancer Institute, Department of Surgery, Anne Arundel Medical Center, Cancer Service Line, Luminis Health, Annapolis, MD, USA.
| | - Yaguang Xi
- Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
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32
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Akbari A, Sedaghat M, Heshmati J, Tabaeian SP, Dehghani S, Pizarro AB, Rostami Z, Agah S. Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers. Biomed Pharmacother 2021; 141:111849. [PMID: 34214729 DOI: 10.1016/j.biopha.2021.111849] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 06/08/2021] [Accepted: 06/24/2021] [Indexed: 02/07/2023] Open
Abstract
Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.
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Affiliation(s)
- Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Meghdad Sedaghat
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Javad Heshmati
- Songhor Healthcare Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seidamir Pasha Tabaeian
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Sadegh Dehghani
- Radiation Sciences Department, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Zahra Rostami
- Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
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33
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Akhlaghipour I, Bina AR, Abbaszadegan MR, Moghbeli M. Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview. Genes Environ 2021; 43:14. [PMID: 33883026 PMCID: PMC8059047 DOI: 10.1186/s41021-021-00187-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 04/07/2021] [Indexed: 11/10/2022] Open
Abstract
Cancer is one of the main health challenges and leading causes of deaths in the world. Various environmental and genetic risk factors are associated with tumorigenesis. Epigenetic deregulations are also important risk factors during tumor progression which are reversible transcriptional alterations without any genomic changes. Various mechanisms are involved in epigenetic regulations such as DNA methylation, chromatin modifications, and noncoding RNAs. Cancer incidence and mortality have a growing trend during last decades among Iranian population which are significantly related to the late diagnosis. Therefore, it is required to prepare efficient molecular diagnostic panels for the early detection of cancer in this population. Promoter hyper methylation is frequently observed as an inhibitory molecular mechanism in various genes associated with DNA repair, cell cycle regulation, and apoptosis during tumor progression. Since aberrant promoter methylations have critical roles in early stages of neoplastic transformations, in present review we have summarized all of the aberrant methylations which have been reported during tumor progression among Iranian cancer patients. Aberrant promoter methylations are targetable and prepare novel therapeutic options for the personalized medicine in cancer patients. This review paves the way to introduce a non-invasive methylation specific panel of diagnostic markers for the early detection of cancer among Iranians.
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Affiliation(s)
- 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
| | | | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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34
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Prinz C, Mese K, Weber D. MicroRNA Changes in Gastric Carcinogenesis: Differential Dysregulation during Helicobacter pylori and EBV Infection. Genes (Basel) 2021; 12:genes12040597. [PMID: 33921696 PMCID: PMC8073778 DOI: 10.3390/genes12040597] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/05/2021] [Accepted: 04/14/2021] [Indexed: 12/11/2022] Open
Abstract
Despite medical advances, gastric-cancer (GC) mortality remains high in Europe. Bacterial infection with Helicobacter pylori (H. pylori) and viral infection with the Epstein–Barr virus (EBV) are associated with the development of both distal and proximal gastric cancer. Therefore, the detection of these infections and the prediction of further cancer development could be clinically significant. To this end, microRNAs (miRNAs) could serve as promising new tools. MiRNAs are highly conserved noncoding RNAs that play an important role in gene silencing, mainly acting via translational repression and the degradation of mRNA targets. Recent reports demonstrate the downregulation of numerous miRNAs in GC, especially miR-22, miR-145, miR-206, miR-375, and miR-490, and these changes seem to promote cancer-cell invasion and tumor spreading. The dysregulation of miR-106b, miR-146a, miR-155, and the Let-7b/c complex seems to be of particular importance during H. pylori infection or gastric carcinogenesis. In contrast, many reports describe changes in host miRNA expression and outline the effects of bamHI-A region rightward transcript (BART) miRNA in EBV-infected tissue. The differential regulation of these miRNA, acting alone or in close interaction when both infections coexist, may therefore enable us to detect cancer earlier. In this review, we focus on the two different etiologies of gastric cancer and outline the molecular pathways through which H. pylori- or EBV-induced changes might synergistically act via miR-155 dysregulation to potentiate cancer risk. The three markers, namely, H. pylori presence, EBV infection, and miR-155 expression, may be checked in routine biopsies to evaluate the risk of developing gastric cancer.
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Affiliation(s)
- Christian Prinz
- Medizinische Klinik 2, Helios Universitätsklinikum Wuppertal, 42283 Wuppertal, Germany;
- Lehrstuhl Innere Medizin 1, University of Witten/Herdecke gGmbH, 42283 Wuppertal, Germany;
- Correspondence: ; Tel.: +49-202-896-2243; Fax: +49-202-896-2740
| | - Kemal Mese
- Lehrstuhl Innere Medizin 1, University of Witten/Herdecke gGmbH, 42283 Wuppertal, Germany;
- Institute of Virology, University of Göttingen, 37075 Göttingen, Germany
| | - David Weber
- Medizinische Klinik 2, Helios Universitätsklinikum Wuppertal, 42283 Wuppertal, Germany;
- Lehrstuhl Innere Medizin 1, University of Witten/Herdecke gGmbH, 42283 Wuppertal, Germany;
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Ouyang J, Xie Z, Lei X, Tang G, Gan R, Yang X. Clinical crosstalk between microRNAs and gastric cancer (Review). Int J Oncol 2021; 58:7. [PMID: 33649806 PMCID: PMC7895535 DOI: 10.3892/ijo.2021.5187] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
Globally, there were over 1 million new gastric cancer (GC) patients in 2018 and GC has become the sixth most common cancer worldwide. GC caused 783,000 deaths worldwide in 2018, making it the third most deadly cancer type. miRNAs are short (~22 nucleotides in length) non‑coding RNA molecules, which can regulate gene expression passively at a post‑transcriptional level. There are more and more in‑depth studies on miRNAs. There are numerous conclusive evidences that there is an inseparable link between miRNAs and GC. miRNAs can affect the entire process of GC, including the oncogenesis, development, diagnosis, treatment and prognosis of GC. Although many miRNAs have been linked to GC, few can be applied to clinical practice. This review takes the clinical changes of GC as a clue and summarizes the miRNAs related to GC that have confirmed the mechanism of action in the past three years. Through in‑depth study and understanding of the mechanism of those miRNAs, we predict their possible clinical uses, and suggest some new insights to overcome GC.
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Affiliation(s)
- Jing Ouyang
- Institute of Pharmacy and Pharmacology, University of South China
| | - Zhizhong Xie
- Institute of Pharmacy and Pharmacology, University of South China
| | - Xiaoyong Lei
- Institute of Pharmacy and Pharmacology, University of South China
| | - Guotao Tang
- Institute of Pharmacy and Pharmacology, University of South China
| | - Runliang Gan
- Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Xiaoyan Yang
- Institute of Pharmacy and Pharmacology, University of South China
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Baghery Saghchy Khorasani A, Pourbagheri-Sigaroodi A, Pirsalehi A, Safaroghli-Azar A, Zali MR, Bashash D. The PI3K/Akt/mTOR signaling pathway in gastric cancer; from oncogenic variations to the possibilities for pharmacologic interventions. Eur J Pharmacol 2021; 898:173983. [PMID: 33647255 DOI: 10.1016/j.ejphar.2021.173983] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 02/13/2021] [Accepted: 02/23/2021] [Indexed: 12/24/2022]
Abstract
Genetic and epigenetic alterations have been under concentrated investigations for many years in order to unearth the molecules regulating human cancer pathogenesis. However, the identification of a wide range of dysregulated genes and their protein products has raised a question regarding how the results of this large collection of alterations could converge into a formation of one malignancy. The answer may be found in the signaling cascades that regulate the survival and metabolism of the cells. Aberrancies of each participant molecule of such cascades may well result in augmented viability and unlimited proliferation of cancer cells. Among various signaling pathways, the phosphatidylinositol-3-kinase (PI3K) axis has been shown to be activated in about one-third of human cancers. One of the malignancies that is mostly affected by this axis is gastric cancer (GC), one of the most fatal cancers worldwide. In the present review, we aimed to illustrate the significance of the PI3K/Akt/mTOR axis in the pathogenesis of GC and also provided a wide perspective about the application of the inhibitors of this axis in the therapeutic strategies of this malignancy.
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Affiliation(s)
| | - Atieh Pourbagheri-Sigaroodi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Pirsalehi
- Department of Internal Medicine, School of Medicine, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ava Safaroghli-Azar
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Clerici SP, Oliveira PFDS, Akagi EM, Cordeiro HG, Azevedo-Martins JM, Faria AVDS, Ferreira-Halder CV. A comprehensive review on the role of protein tyrosine phosphatases in gastric cancer development and progression. Biol Chem 2021; 402:663-674. [PMID: 33544466 DOI: 10.1515/hsz-2020-0355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 01/15/2021] [Indexed: 12/09/2022]
Abstract
The main post-translational reversible modulation of proteins is phosphorylation and dephosphorylation, catalyzed by protein kinases (PKs) and protein phosphatases (PPs) which is crucial for homeostasis. Imbalance in this crosstalk can be related to diseases, including cancer. Plenty of evidence indicates that protein tyrosine phosphatases (PTPs) can act as tumor suppressors and tumor promoters. In gastric cancer (GC), there is a lack of understanding of the molecular aspects behind the tumoral onset and progression. Here we describe several members of the PTP family related to gastric carcinogenesis. We discuss the associated molecular mechanisms which support the down or up modulation of different PTPs. We emphasize the Helicobacter pylori (H. pylori) virulence which is in part associated with the activation of PTP receptors. We also explore the involvement of intracellular redox state in response to H. pylori infection. In addition, some PTP members are under influence by genetic mutations, epigenetics mechanisms, and miRNA modulation. The understanding of multiple aspects of PTPs in GC may provide new targets and perspectives on drug development.
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Affiliation(s)
- Stefano Piatto Clerici
- Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Rua Monteiro Lobato 255, 13083-862Campinas, São Paulo, Brazil
| | | | - Erica Mie Akagi
- Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Rua Monteiro Lobato 255, 13083-862Campinas, São Paulo, Brazil
| | - Helon Guimarães Cordeiro
- Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Rua Monteiro Lobato 255, 13083-862Campinas, São Paulo, Brazil
| | - Jordana Maria Azevedo-Martins
- Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Rua Monteiro Lobato 255, 13083-862Campinas, São Paulo, Brazil
| | - Alessandra Valéria de Sousa Faria
- Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Rua Monteiro Lobato 255, 13083-862Campinas, São Paulo, Brazil
| | - Carmen Veríssima Ferreira-Halder
- Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Rua Monteiro Lobato 255, 13083-862Campinas, São Paulo, Brazil
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Abstract
PURPOSE One of the most important serious malignancies is gastric cancer (GC) with a high mortality globally. In this way, beside the environmental factors, genetic parameter has a remarkable effective fluctuation in GC. Correspondingly, telomeres are nucleoprotein structures measuring the length of telomeres and they have special potential in diagnosis of various types of cancers. Defect protection of the telomeric length initiates the instability of the genome during cancer, including gastric cancer. The most common way of maintaining telomere length is the function of the telomerase enzyme that replicates the TTAGGG to the end of the 3' chromosome. METHODS In this review, we want to discuss the alterations of hTERT repression on the modification of TERRA gene expression in conjunction with the importance of telomere and telomerase in GC. RESULTS The telomerase enzyme contains two essential components called telomerase reverse transcriptase (hTERT) and RNA telomerase (hTR, hTERC). Deregulation of hTERT plays a key role in the multistage process of tumorigenicity and anticancer drug resistance. The direct relationship between telomerase activity and hTERT has led to hTERT to be considered a key target for cancer treatment. Recent results show that telomeres are transcribed into telomeric repeat-containing RNA (TERRA) in mammalian cells and are long noncoding RNAs (lncRNAs) identified in different tissues. In addition, most chemotherapy methods have a lot of side effects on normal cells. CONCLUSION Telomere and telomerase are useful therapeutic goal. According to the main roles of hTERT in tumorigenesis, growth, migration, and cancer invasion, hTERT and regulatory mechanisms that control the expression of hTERT are attractive therapeutic targets for cancer treatment.
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Ahadi A. A systematic review of microRNAs as potential biomarkers for diagnosis and prognosis of gastric cancer. Immunogenetics 2021; 73:155-161. [PMID: 33399935 DOI: 10.1007/s00251-020-01201-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 12/10/2020] [Indexed: 02/08/2023]
Abstract
Gastric cancer (GC) is the third leading cause of global cancer morbidity and mortality. One of the significant challenges in GC treatment is that most GC patients are diagnosed with advanced-stage disease due to the lack of suitable biomarkers. Recent studies have shown that microRNAs (miRNAs) can acts as a potential biomarker in GC diagnosis and prognosis. I performed a systematic review of published miRNA studies in GC, which includes the miRNA expression profiles between GC tissues and normal tissues and also miRNA studies to evaluate their potential value in the diagnosis and prognosis of GC. Among the studies, upregulation of miR-21, miR-106b, miR-25, miR-214, miR-18a, miR-191, and miR-93 and downregulation of miR-375, miR-148a, miR-92, miR-155, and miR-564 were observed in GC tissues. In evaluating of diagnosis value of miRNAs, the study was performed on a combined miRNA include miR-21, miR-93, miR-106a, and miR-106b indicated the panel of these miRNAs have the highest AUC 0.887 to discriminate GC patients from healthy. Also, miR-940 with a sensitivity of 81.25% and specificity of 98.57% may be used for diagnostic biomarkers for GC. Finally, the pooled prognostic result of miR-21 for hazard ratios (HR) was 1.260 (95% CI 0.370-4.330, P < 0.001), showing that miR-21 could predict poor survival in GC patients. This systematic review can confirm that we need to find a miRNA or a panel of miRNAs with high sensitivity and specificity for further exploration to investigate a better diagnostic or therapeutic tool for personalized management of GC patients.
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Affiliation(s)
- Alireza Ahadi
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Mollasalehi H, Shajari E. A colorimetric nano-biosensor for simultaneous detection of prevalent cancers using unamplified cell-free ribonucleic acid biomarkers. Bioorg Chem 2020; 107:104605. [PMID: 33421955 DOI: 10.1016/j.bioorg.2020.104605] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 12/12/2020] [Accepted: 12/25/2020] [Indexed: 12/29/2022]
Abstract
Early detection of cancer increases the chance of effective treatment and survival rates. The aim of this study is to develop a rapid and non-invasive nano-biosensing method to screen common lethal cancers in their early stages. In that regard, two circulating microRNA (miR-21, miR-155) biomarkers, which are upregulated in plasma in prevalent cancers, were targeted by a rapid and colorimetric nano-biosensor based on non-crosslinking Au-nanoprobes without amplification requirement. Multiple cancerous cell lines, including A549, MCF7, HT-29, A2780, AGS, MKN-45, and SW-1736 and the primary fibroblast were examined with naked eyes after the hybridization assay using exogenous biomarkers. The results were also confirmed by spectroscopy analysis. The upregulated miRNAs in cancerous cell lines caused a significant blue shift in the Au-nanoprobe absorbance spectrum while the samples isolated from normal cells remained intact red. The limit of detection (LOD) of the method was determined to be less than one ng/µL of total isolated miRNA using an instrument-free visual method. The developed geno-sensing method could serve as a simple, point-of-care platform for cancer prognosis and diagnosis, leading to operative nano-theranostics.
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Affiliation(s)
- Hamidreza Mollasalehi
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Velenjak, Tehran Postal Code: 1983969411, Iran.
| | - Elmira Shajari
- Protein Research Center (PRC), Shahid Beheshti University, Velenjak, Tehran, Iran
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Afshari A, Janfeshan S, Yaghobi R, Roozbeh J, Azarpira N. Covid-19 pathogenesis in prostatic cancer and TMPRSS2-ERG regulatory genetic pathway. INFECTION GENETICS AND EVOLUTION 2020; 88:104669. [PMID: 33301988 PMCID: PMC7720011 DOI: 10.1016/j.meegid.2020.104669] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/09/2020] [Accepted: 12/04/2020] [Indexed: 12/11/2022]
Abstract
Members of Coronaviridae family have been the source of respiratory illnesses. The outbreak of SARS-CoV-2 that produced a severe lung disease in afflicted patients in China and other countries was the reason for the incredible attention paid toward this viral infection. It is known that SARS-CoV-2 is dependent on TMPRSS2 activity for entrance and subsequent infection of the host cells and TMPRSS2 is a host cell molecule that is important for the spread of viruses such as coronaviruses. Different factors can increase the risk of prostate cancer, including older age, a family history of the disease. Androgen receptor (AR) initiates a transcriptional cascade which plays a serious role in both normal and malignant prostate tissues. TMPRSS2 protein is highly expressed in prostate secretory epithelial cells, and its expression is dependent on androgen signals. One of the molecular signs of prostate cancer is TMPRSS2-ERG gene fusion. In TMPRSS2-ERG-positive prostate cancers different patterns of changed gene expression can be detected. The possible molecular relation between fusion positive prostate cancer patients and the increased risk of lethal respiratory viral infections especially SARS-CoV-2 can candidate TMPRSS2 as an attractive drug target. The studies show that some molecules such as nicotinamide, PARP1, ETS and IL-1R can be studied deeper in order to control SARS-CoV-2 infection especially in prostate cancer patients. This review attempts to investigate the possible relation between the gene expression pattern that is produced through TMPRSS2-ERG fusion positive prostate cancer and the possible influence of these fluctuations on the pathogenesis and development of viral infections such as SARS-CoV-2.
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Affiliation(s)
- Afsoon Afshari
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sahar Janfeshan
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ramin Yaghobi
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jamshid Roozbeh
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Negar Azarpira
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Yan Z, Yin H, Lin G. CircDDX42 Accelerates the Development of Pancreatic Cancer via miR-613/ID4/PI3K/AKT Axis. Onco Targets Ther 2020; 13:10945-10957. [PMID: 33149610 PMCID: PMC7604853 DOI: 10.2147/ott.s233000] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/15/2020] [Indexed: 01/01/2023] Open
Abstract
Background Pancreatic cancer (PC) is one of the fatal cancers globally. CircDEAD-box helicase 42 (circDDX42) has been reported to play an oncogenic role in many cancers. The purpose of our study was to explore the relationship between circDDX42 and PC development and the potential mechanism by which circDDX42 modulating the progression of PC. Methods The enrichment of circDDX42, miR-613 and inhibitor of DNA binding 4 (ID4) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) in PC tissues and cells. The proliferation, apoptosis and metastasis of PC cells were examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Western blot, flow cytometry and transwell migration and invasion assays, respectively. The binding sites between miR-613 and circDDX42 or ID4 were predicted by Starbase bioinformatic software, and dual-luciferase reporter assay was conducted to verify the combination between miR-613 and circDDX42 or ID4. Western blot was carried out to detect the abundance of ID4, p-phosphatidylinositol 3-kinase (p-PI3K), PI3K, p-AKT serine/threonine kinase (p-AKT) and AKT in PC cells. The in vivo role of circDDX42 was verified through using murine xenograft model. Results The level of circDDX42 was enhanced in PC tissues and cells compared with that in matching normal tissues and HPDE cells. CircDDX42 promoted the proliferation and metastasis and suppressed the apoptosis of PC cells. CircDDX42 could sponge miR-613, and miR-613 was negatively regulated by circDDX42 in PC cells. MiR-613 suppressed the progression of PC. ID4 was a direct target of miR-613. ID4 was inversely modulated by miR-613 and positively regulated by circDDX42 in PC cells. ID4 played an oncogenic role in the tumorigenesis of PC. CircDDX42/miR-613/ID4 axis regulated the activation of PI3K/AKT pathway in PC cells. ID4 facilitated the progression of PC via activating PI3K/AKT signal pathway. CircDDX42 promoted the tumor growth of PC in vivo. Conclusion CircDDX42 accelerated the proliferation and metastasis while impeded the apoptosis of PC cells via circDDX42/miR-613/ID4/PI3K/AKT axis. This axis might be a promising target for PC therapy.
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Affiliation(s)
- Zhen Yan
- Department of General Surgery, The First Hospital of Qiqihar, Qiqihar 161005, People's Republic of China.,Department of General Surgery, Qiqihar Hospital Affiliated to Southern Medical University, Qiqihar 161005, People's Republic of China
| | - Heliang Yin
- Department of General Surgery, The First Hospital of Qiqihar, Qiqihar 161005, People's Republic of China.,Department of General Surgery, Qiqihar Hospital Affiliated to Southern Medical University, Qiqihar 161005, People's Republic of China
| | - Guoying Lin
- Department of General Surgery, The First Hospital of Qiqihar, Qiqihar 161005, People's Republic of China.,Department of General Surgery, Qiqihar Hospital Affiliated to Southern Medical University, Qiqihar 161005, People's Republic of China
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Fukada M, Matsuhashi N, Takahashi T, Sugito N, Heishima K, Akao Y, Yoshida K. Tumor Tissue MIR92a and Plasma MIRs21 and 29a as Predictive Biomarkers Associated with Clinicopathological Features and Surgical Resection in a Prospective Study on Colorectal Cancer Patients. J Clin Med 2020; 9:jcm9082509. [PMID: 32759718 PMCID: PMC7465950 DOI: 10.3390/jcm9082509] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 07/15/2020] [Accepted: 07/29/2020] [Indexed: 12/21/2022] Open
Abstract
Cancer-related microRNAs (miRNAs) are emerging as non-invasive biomarkers for colorectal cancer (CRC). This study aimed to analyze the correlation between the levels of tissue and plasma miRNAs and clinicopathological characteristics and surgical resection. This study was a prospective study of CRC patients who underwent surgery. Forty-four sample pairs of tissue and plasma were analyzed. The miRNA levels were evaluated by RT-qPCR. The level of tumor tissue MIR92a showed a significant difference in CRC with lymph node metastasis, stage ≥ III, and high lymphatic invasion. In preoperative plasma, there were significant differences in CRC with stage ≥ III (MIR29a) and perineural invasion (MIR21). In multivariate analysis of lymphatic invasion, the levels of both preoperative plasma MIR29a and tumor tissue MIR92a showed significant differences. Furthermore, in cases with higher plasma miRNA level, the levels of plasma MIRs21 and 29a were significantly decreased after the operation. In this study, there were significant differences in miRNAs levels with respect to the sample type, clinicopathological features, and surgical resection. The levels of tumor tissue MIR92a and preoperative plasma MIR29a may have the potential as a biomarker for prognosis. The plasma MIRs21 and 29a level has the potential to be a predictive biomarker for treatment efficacy.
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Affiliation(s)
- Masahiro Fukada
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
| | - Nobuhisa Matsuhashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
| | - Takao Takahashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
| | - Nobuhiko Sugito
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (N.S.); (K.H.); (Y.A.)
| | - Kazuki Heishima
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (N.S.); (K.H.); (Y.A.)
| | - Yukihiro Akao
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (N.S.); (K.H.); (Y.A.)
| | - Kazuhiro Yoshida
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu City 501-1194, Japan; (M.F.); (N.M.); (T.T.)
- Correspondence: ; Tel.: +81-058-230-6235
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Ashrafizadeh M, Najafi M, Ang HL, Moghadam ER, Mahabady MK, Zabolian A, Jafaripour L, Bejandi AK, Hushmandi K, Saleki H, Zarrabi A, Kumar AP. PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation. Biomedicines 2020; 8:E264. [PMID: 32756305 PMCID: PMC7460532 DOI: 10.3390/biomedicines8080264] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 07/23/2020] [Accepted: 07/23/2020] [Indexed: 02/06/2023] Open
Abstract
Cancer is one of the life-threatening disorders that, in spite of excellent advances in medicine and technology, there is no effective cure for. Surgery, chemotherapy, and radiotherapy are extensively applied in cancer therapy, but their efficacy in eradication of cancer cells, suppressing metastasis, and improving overall survival of patients is low. This is due to uncontrolled proliferation of cancer cells and their high migratory ability. Finding molecular pathways involved in malignant behavior of cancer cells can pave the road to effective cancer therapy. In the present review, we focus on phosphatase and tensin homolog (PTEN) signaling as a tumor-suppressor molecular pathway in gastric cancer (GC). PTEN inhibits the PI3K/Akt pathway from interfering with the migration and growth of GC cells. Its activation leads to better survival of patients with GC. Different upstream mediators of PTEN in GC have been identified that can regulate PTEN in suppressing growth and invasion of GC cells, such as microRNAs, long non-coding RNAs, and circular RNAs. It seems that antitumor agents enhance the expression of PTEN in overcoming GC. This review focuses on aforementioned topics to provide a new insight into involvement of PTEN and its downstream and upstream mediators in GC. This will direct further studies for evaluation of novel signaling networks and their targeting for suppressing GC progression.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran;
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran;
| | - Hui Li Ang
- Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore;
| | - Ebrahim Rahmani Moghadam
- Department of Anatomical Sciences, School of Medicine, Student Research Committee, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran;
- Kazerun Health Technology Incubator, Shiraz University of Medical Sciences, Shiraz 6461665145, Iran
| | - Mahmood Khaksary Mahabady
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan 8715988141, Iran;
| | - Amirhossein Zabolian
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; (A.Z.); (A.K.B.); (H.S.)
| | - Leila Jafaripour
- Department of Anatomy, School of Medicine, Dezful University of Medical Sciences, Dezful 3419759811, Iran;
| | - Atefe Kazemzade Bejandi
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; (A.Z.); (A.K.B.); (H.S.)
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417414418, Iran;
| | - Hossein Saleki
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; (A.Z.); (A.K.B.); (H.S.)
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla 34956, Istanbul, Turkey
- Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla 34956, Istanbul, Turkey
| | - Alan Prem Kumar
- Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore;
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Hallal S, Ebrahim Khani S, Wei H, Lee MYT, Sim HW, Sy J, Shivalingam B, Buckland ME, Alexander-Kaufman KL. Deep Sequencing of Small RNAs from Neurosurgical Extracellular Vesicles Substantiates miR-486-3p as a Circulating Biomarker that Distinguishes Glioblastoma from Lower-Grade Astrocytoma Patients. Int J Mol Sci 2020; 21:ijms21144954. [PMID: 32668808 PMCID: PMC7404297 DOI: 10.3390/ijms21144954] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 07/01/2020] [Accepted: 07/07/2020] [Indexed: 02/07/2023] Open
Abstract
Extracellular vesicles (EVs) play key roles in glioblastoma (GBM; astrocytoma grade IV) biology and are novel sources of biomarkers. EVs released from GBM tumors can cross the blood-brain-barrier into the periphery carrying GBM molecules, including small non-coding RNA (sncRNA). Biomarkers cargoed in circulating EVs have shown great promise for assessing the molecular state of brain tumors in situ. Neurosurgical aspirate fluids captured during tumor resections are a rich source of GBM-EVs isolated directly from tumor microenvironments. Using density gradient ultracentrifugation, EVs were purified from cavitron ultrasonic surgical aspirate (CUSA) washings from GBM (n = 12) and astrocytoma II-III (GII-III, n = 5) surgeries. The sncRNA contents of surgically captured EVs were profiled using the Illumina® NextSeqTM 500 NGS System. Differential expression analysis identified 27 miRNA and 10 piRNA species in GBM relative to GII-III CUSA-EVs. Resolved CUSA-EV sncRNAs could discriminate serum-EV sncRNA profiles from GBM and GII-III patients and healthy controls and 14 miRNAs (including miR-486-3p and miR-106b-3p) and cancer-associated piRNAs (piR_016658, _016659, _020829 and _204090) were also significantly expressed in serum-EVs. Circulating EV markers that correlate with histological, neuroradiographic and clinical parameters will provide objective measures of tumor activity and improve the accuracy of GBM tumor surveillance.
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Affiliation(s)
- Susannah Hallal
- Department of Neurosurgical Services, Chris O’Brien Lifehouse, Camperdown 2050, Australia; (S.H.); (B.S.)
- Discipline of Pathology, School of Medical Sciences, The University of Sydney, Camperdown 2006, Australia; (S.E.K.); (M.E.B.)
- Brainstorm Brain Cancer Research, Brain and Mind Centre, The University of Sydney, Camperdown 2050, Australia; (H.W.); (M.Y.T.L.)
- Neuropathology Department, Royal Prince Alfred Hospital, Camperdown 2050, Australia;
| | - Saeideh Ebrahim Khani
- Discipline of Pathology, School of Medical Sciences, The University of Sydney, Camperdown 2006, Australia; (S.E.K.); (M.E.B.)
| | - Heng Wei
- Brainstorm Brain Cancer Research, Brain and Mind Centre, The University of Sydney, Camperdown 2050, Australia; (H.W.); (M.Y.T.L.)
- Neuropathology Department, Royal Prince Alfred Hospital, Camperdown 2050, Australia;
| | - Maggie Yuk Ting Lee
- Brainstorm Brain Cancer Research, Brain and Mind Centre, The University of Sydney, Camperdown 2050, Australia; (H.W.); (M.Y.T.L.)
- Neuropathology Department, Royal Prince Alfred Hospital, Camperdown 2050, Australia;
| | - Hao-Wen Sim
- Department of Medical Oncology and NHMRC Clinical Trials Centre, Chris O’Brien Lifehouse, Camperdown 2050, Australia;
- Central Clinical School, The University of Sydney, Camperdown 2006, Australia
- The Kinghorn Cancer Centre, St Vincent’s Hospital, Darlinghurst 2010, Australia
| | - Joanne Sy
- Neuropathology Department, Royal Prince Alfred Hospital, Camperdown 2050, Australia;
| | - Brindha Shivalingam
- Department of Neurosurgical Services, Chris O’Brien Lifehouse, Camperdown 2050, Australia; (S.H.); (B.S.)
- Brainstorm Brain Cancer Research, Brain and Mind Centre, The University of Sydney, Camperdown 2050, Australia; (H.W.); (M.Y.T.L.)
| | - Michael E. Buckland
- Discipline of Pathology, School of Medical Sciences, The University of Sydney, Camperdown 2006, Australia; (S.E.K.); (M.E.B.)
- Brainstorm Brain Cancer Research, Brain and Mind Centre, The University of Sydney, Camperdown 2050, Australia; (H.W.); (M.Y.T.L.)
- Neuropathology Department, Royal Prince Alfred Hospital, Camperdown 2050, Australia;
| | - Kimberley L. Alexander-Kaufman
- Department of Neurosurgical Services, Chris O’Brien Lifehouse, Camperdown 2050, Australia; (S.H.); (B.S.)
- Discipline of Pathology, School of Medical Sciences, The University of Sydney, Camperdown 2006, Australia; (S.E.K.); (M.E.B.)
- Brainstorm Brain Cancer Research, Brain and Mind Centre, The University of Sydney, Camperdown 2050, Australia; (H.W.); (M.Y.T.L.)
- Neuropathology Department, Royal Prince Alfred Hospital, Camperdown 2050, Australia;
- Correspondence: ; Tel.: +61-2-8514-0675
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Solomon MC, Radhakrishnan RA. MicroRNA's - The vibrant performers in the oral cancer scenario. JAPANESE DENTAL SCIENCE REVIEW 2020; 56:85-89. [PMID: 32612717 PMCID: PMC7310692 DOI: 10.1016/j.jdsr.2020.04.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/11/2020] [Accepted: 04/13/2020] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are a family of small non-coding (18–22 nucleotide) RNA molecules. These molecules regulate gene expression by either inhibiting mRNA translation or by degrading mRNA. A single miRNA can control the expression of target genes, and the expression of a target gene can be regulated by multiple miRNAs. They are key regulators of various biological and pathological processes. These include cell proliferation, development and tumorigenesis. Novel studies have discovered definite signature miRNAs in the initiation and progression of cancers. Interestingly, miRNAs have also been found in fragile genomic sites that are associated with increased cancer risk. These micro RNAs regulate the expression of several genes that play a crucial role in the transition of normal oral mucosa through dysplasia to malignancy. The aim of this review is to recapitulate the current understanding of the many miRNAs that have been identified, the genes that they target and the role that they play in the carcinogenic pathway. The review also highlights the prospective role of miRNAs in the diagnosis, prognosis and treatment of oral cancers.
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Affiliation(s)
- Monica Charlotte Solomon
- Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Raghu Anekal Radhakrishnan
- Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal, Wellcome Trust/DBT India Alliance Fellow, Director, International Relations, Manipal Academy of Higher Education, Manipal, Karnataka, India
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Sun X, Xu H, Huang T, Zhang C, Wu J, Luo S. Simultaneous delivery of anti-miRNA and docetaxel with supramolecular self-assembled "chitosome" for improving chemosensitivity of triple negative breast cancer cells. Drug Deliv Transl Res 2020; 11:192-204. [PMID: 32394334 DOI: 10.1007/s13346-020-00779-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
At present, treating of triple negative breast cancer (TNBC) mainly depends on chemotherapy with more toxic side effects, but the effect is limited and it is highly prone to drug resistance. Gene therapy using anti-microRNAs maybe one of alternative therapeutic strategies. Due to the poor cell permeability and significant in vivo decomposition rate of anti-microRNAs, which limits their clinical application, we developed a core-shell supramolecular nanovector of "chitosome" that were self-assembled from the synthetic amphiphilic chitosan derivatives. The constructed chitosomes could co-load hydrophilic anti-miR-21 and hydrophobic docetaxel (DTX) into one combo nanocarrier with entrapment efficiency of more than 80%, as well as spherical morphology and average particle size of 90 nm. In comparison with the naked ones, anti-miR-21 encapsulated with chitosomes showed significantly increased cellular transfection and stability against degradation by nuclease in serum. Compared with DTX or anti-miR-21 formulations used alone, the co-delivery of the two drugs with the combo chitosome obtained improved chemosensitivity of TNBC cells to DTX treatment through their synergistic mechanisms. Taken together, the developed chitosome could be a promising candidate for simultaneous delivery of insoluble chemotherapeutic drugs and gene agents for TNBC therapy. Graphical abstract.
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Affiliation(s)
- Xianfu Sun
- Department of Breast Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China
| | - Haipeng Xu
- Department of Thoracic Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, 350014, Fujian, China
| | - Tao Huang
- Department of Breast Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China
| | - Chengjuan Zhang
- Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China
| | - Junzhao Wu
- Department of Breast Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China
| | - Suxia Luo
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China.
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Ahadi A. Dysregulation of miRNAs as a signature for diagnosis and prognosis of gastric cancer and their involvement in the mechanism underlying gastric carcinogenesis and progression. IUBMB Life 2020; 72:884-898. [DOI: 10.1002/iub.2259] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 02/08/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Alireza Ahadi
- Department of Medical Genetics, School of MedicineShahid Beheshti University of Medical Sciences Tehran Iran
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Magnelli L, Schiavone N, Staderini F, Biagioni A, Papucci L. MAP Kinases Pathways in Gastric Cancer. Int J Mol Sci 2020; 21:ijms21082893. [PMID: 32326163 PMCID: PMC7215608 DOI: 10.3390/ijms21082893] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 04/05/2020] [Accepted: 04/17/2020] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is turning out today to be one of the most important welfare issues for both Asian and European countries. Indeed, while the vast majority of the disease burden is located in China and in Pacific and East Asia, GC in European countries still account for about 100,000 deaths per year. With this review article, we aim to focus the attention on one of the most complex cellular pathways involved in GC proliferation, invasion, migration, and metastasis: the MAP kinases. Such large kinases family is to date constantly studied, since their discovery more than 30 years ago, due to the important role that it plays in the regulation of physiological and pathological processes. Interactions with other cellular proteins as well as miRNAs and lncRNAs may modulate their expression influencing the cellular biological features. Here, we summarize the most important and recent studies involving MAPK in GC. At the same time, we need to underly that, differently from cancers arising from other tissues, where MAPK pathways seems to be a gold target for anticancer therapies, GC seems to be unique in any aspect. Our aim is to review the current knowledge in MAPK pathways alterations leading to GC, including H. pylori MAPK-triggering to derail from gastric normal epithelium to GC and to encourage researches involved in MAPK signal transduction, that seems to definitely sustain GC development.
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Affiliation(s)
- Lucia Magnelli
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B. Morgagni 50, 50134 Firenze, Italy; (N.S.); (A.B.); (L.P.)
- Correspondence: ; Tel.: +39-055-2751397
| | - Nicola Schiavone
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B. Morgagni 50, 50134 Firenze, Italy; (N.S.); (A.B.); (L.P.)
| | - Fabio Staderini
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy;
| | - Alessio Biagioni
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B. Morgagni 50, 50134 Firenze, Italy; (N.S.); (A.B.); (L.P.)
| | - Laura Papucci
- Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B. Morgagni 50, 50134 Firenze, Italy; (N.S.); (A.B.); (L.P.)
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50
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Zhu XD, Gao ZJ, Zheng GD. miR-125a-5p inhibits cancer stem cells phenotype and epithelial to mesenchymal transition in glioblastoma. Rev Assoc Med Bras (1992) 2020; 66:445-451. [PMID: 32578777 DOI: 10.1590/1806-9282.66.4.445] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 10/10/2019] [Indexed: 01/08/2023] Open
Abstract
SUMMARY OBJECTIVE Glioblastoma (GBM) is a common type of cancer with high mortality. Epithelial to mesenchymal transition (EMT) plays a vital role in the development of glioblastoma. The aim of this study is to evaluate the role of miR-125a-5p in glioblastoma and in the tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. METHODS The role of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma was measured in this study. RESULTS We showed the roles of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma. miR-125a-5p can inhibit the CSCs phenotype and EMT in glioblastoma cells. In addition, its over-expression can significantly regulate CSCs-associated genes and EMT-associated gene expression in glioblastoma cells. CONCLUSIONS We concluded that miR-125a-5p is one of the key microRNAs regulating CSCs and EMT programs in glioblastoma. The results suggested that miR-125a-5p might be a novel therapy target for glioblastoma.
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