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Gila F, Khoddam S, Jamali Z, Ghasemian M, Shakeri S, Dehghan Z, Fallahi J. Personalized medicine in colorectal cancer: a comprehensive study of precision diagnosis and treatment. Per Med 2025; 22:59-81. [PMID: 39924822 DOI: 10.1080/17410541.2025.2459050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 01/23/2025] [Indexed: 02/11/2025]
Abstract
Colorectal cancer is a common and fatal disease that affects many people globally. CRC is classified as the third most prevalent cancer among males and the second most frequent cancer among females worldwide. The purpose of this article is to examine how personalized medicine might be used to treat colorectal cancer. The classification of colorectal cancer based on molecular profiling, including the detection of significant gene mutations, genomic instability, and gene dysregulation, is the main topic of this discussion. Advanced technologies and biomarkers are among the detection methods that are explored, demonstrating their potential for early diagnosis and precise prognosis. In addition, the essay explores the world of treatment possibilities by providing light on FDA-approved personalized medicine solutions that provide individualized and precise interventions based on patient characteristics. This article assesses targeted treatments like cetuximab and nivolumab, looks at the therapeutic usefulness of biomarkers like microsatellite instability (MSI) and circulating tumor DNA (ctDNA), and investigates new approaches to combat resistance. Through this, our review provides a thorough overview of personalized medicine in the context of colorectal cancer, ultimately highlighting its potential to revolutionize the field and improve patient care.
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Affiliation(s)
- Fatemeh Gila
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Somayeh Khoddam
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Jamali
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohmmad Ghasemian
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shayan Shakeri
- Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zeinab Dehghan
- Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jafar Fallahi
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
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2
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Walter CEJ, Shankaran ZS, Kontham SS, Ramachandran K, Prakash N, Johnson T, JR SN. Investigating the association of microRNA polymorphisms and lifestyle factors with the susceptibility to common gastrointestinal cancers in an Indian population- A case control study. Heliyon 2025; 11:e41519. [PMID: 39850417 PMCID: PMC11755044 DOI: 10.1016/j.heliyon.2024.e41519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 12/04/2024] [Accepted: 12/25/2024] [Indexed: 01/25/2025] Open
Abstract
The cancers of the gastrointestinal (GI) tract have become a common diagnosis worldwide contributing to a large number of mortalities. Though potentially curable they are mostly fatal due to late diagnosis and lack of accurate diagnostic markers. microRNA, micromanagers of gene expression have been associated to have distinct roles as oncogenes or tumour suppressors in several cancers including GI cancers. These miRNAs are known to harbour single nucleotide polymorphisms (SNPs) that lead to loss or gain of its functions and have been found to be associated with altering susceptibility of several cancers. The current study aimed to investigate the role of miRSNPs in common gastrointestinal cancers. A case control study was designed which included 210 GI cancer cases and 230 cancer free controls. The miRSNPs were successfully genotyped using MassARRAY technique. Association analysis revealed that miR-196a; rs11614913, pre-mir-423; rs6505162, pre-mir-605; rs2043556, pre-mir-149; rs2292832 and pri-mir-30c; rs928508 polymorphisms significantly altered the risk of common GI cancers. Multifactor dimensionality reduction analysis demonstrated that miRSNPs alter GI cancer risk by interacting with exposures like diabetes mellitus, alcohol consumption, diet and socioeconomic status in the study subjects. In conclusion it was found that presence of miRNA polymorphism and certain lifestyle factors alters susceptibility to GI cancers significantly.
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Affiliation(s)
- Charles Emmanuel Jebaraj Walter
- Department of Biotechnology, Sri Ramachandra Institute of Higher Education & Research (formerly Sri Ramachandra Medical College & Research Institute), Chennai, India
| | - Zioni Sangeetha Shankaran
- Department of Biotechnology, Sri Ramachandra Institute of Higher Education & Research (formerly Sri Ramachandra Medical College & Research Institute), Chennai, India
- Biomedical Sciences, Faculty of Allied Health Sciences, Sree Balaji Medical College & Hospital, Chennai, India
| | - Sai Sushmitha Kontham
- Department of Biotechnology, Sri Ramachandra Institute of Higher Education & Research (formerly Sri Ramachandra Medical College & Research Institute), Chennai, India
- Department of Medical Biotechnology, School of Allied Health Sciences, Malla Reddy University, Hyderabad, India
| | | | - Nandini Prakash
- Department of Biotechnology, Sri Ramachandra Institute of Higher Education & Research (formerly Sri Ramachandra Medical College & Research Institute), Chennai, India
| | - Thanka Johnson
- Department of Pathology, Sree Balaji Medical College & Hospital, Chennai, India
| | - Sri Nisha JR
- Department of Prosthodontia, Sree Balaji Dental College & Hospital, Bharath Institute of Higher Education & Research, Chennai, India
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Alves Dos Santos K, Costa Alves de Sousa LM, Costa de Souza KS, Amigo OM, Luchessi AD, Silbiger VN. mirSNPs as Potential Colorectal Cancer Biomarkers: A Systematic Review. Int J Mol Sci 2024; 25:12975. [PMID: 39684686 DOI: 10.3390/ijms252312975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 11/27/2024] [Accepted: 11/29/2024] [Indexed: 12/18/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common neoplasm in the world and the second with the highest mortality rate. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes known as mirSNPs may be related to dysregulated miRNA expression in several neoplasms. This systematic review aims to investigate studies that investigate SNPs located in regions of miRNA genes that influence their expression and are associated with CRC, as well as their potential as biomarkers for the disease, based on the available literature. For this, searches were performed in public databases, including MEDLINE/PubMed, Embase, Web of Science, and Scopus. The rigorous review of the PRISMA 2020 guidelines and the methodological quality of these studies was assessed using the Newcastle-Ottawa scale and the Mixed Methods Assessment Tool. Of the 175 studies identified, 26 were considered eligible: 18 of them highlighted mirSNPs as potential biomarkers of risk and prognosis for CRC; 4 studies suggested a protective role; 1 study linked mirSNPs to treatment; 3 studies found no relevant evidence. These results highlight the importance of conducting further research on the topic, given the potential of these biomarkers to contribute to risk assessment, prognosis, and the development of therapeutic strategies for patients with CRC.
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Affiliation(s)
- Katiusse Alves Dos Santos
- Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
| | | | - Karla Simone Costa de Souza
- Department of Clinical and Toxicological, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
| | - Olalla Maroñas Amigo
- Pharmacogenomics and Drug Discovery (GenDeM), Foundation of Health Research Institute of Santiago de Compostela (FIDIS), 15782 Galicia, Spain
- Genomic Medicine Group, Galician Public Foundation for Genomic Medicine (FPGMX), 15782 Galicia, Spain
| | - André Ducati Luchessi
- Department of Clinical and Toxicological, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
| | - Vivian Nogueira Silbiger
- Department of Clinical and Toxicological, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
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Jiang G, Reiter JL, Dong C, Wang Y, Fang F, Jiang Z, Liu Y. Genetic Regulation of Human isomiR Biogenesis. Cancers (Basel) 2023; 15:4411. [PMID: 37686687 PMCID: PMC10486453 DOI: 10.3390/cancers15174411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/31/2023] [Accepted: 08/31/2023] [Indexed: 09/10/2023] Open
Abstract
MicroRNAs play a critical role in regulating gene expression post-transcriptionally. Variations in mature microRNA sequences, known as isomiRs, arise from imprecise cleavage and nucleotide substitution or addition. These isomiRs can target different mRNAs or compete with their canonical counterparts, thereby expanding the scope of miRNA post-transcriptional regulation. Our study investigated the relationship between cis-acting single-nucleotide polymorphisms (SNPs) in precursor miRNA regions and isomiR composition, represented by the ratio of a specific 5'-isomiR subtype to all isomiRs identified for a particular mature miRNA. Significant associations between 95 SNP-isomiR pairs were identified. Of note, rs6505162 was significantly associated with both the 5'-extension of hsa-miR-423-3p and the 5'-trimming of hsa-miR-423-5p. Comparison of breast cancer and normal samples revealed that the expression of both isomiRs was significantly higher in tumors than in normal tissues. This study sheds light on the genetic regulation of isomiR maturation and advances our understanding of post-transcriptional regulation by microRNAs.
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Affiliation(s)
- Guanglong Jiang
- Department of BioHealth Informatics, Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, IN 46202, USA
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Jill L. Reiter
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Chuanpeng Dong
- Department of Genetics, Yale University, New Haven, CT 06510, USA
| | - Yue Wang
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Fang Fang
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Zhaoyang Jiang
- Department of Computer Science, Purdue University, West Lafayette, IN 47907, USA
| | - Yunlong Liu
- Department of BioHealth Informatics, Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, IN 46202, USA
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Kulkarni A, Gayathrinathan S, Nair S, Basu A, Al-Hilal TA, Roy S. Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities. Cells 2022; 11:2448. [PMID: 35954293 PMCID: PMC9367924 DOI: 10.3390/cells11152448] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/31/2022] [Accepted: 08/03/2022] [Indexed: 01/17/2023] Open
Abstract
Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.
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Affiliation(s)
- Aditi Kulkarni
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
- Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Sharan Gayathrinathan
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Soumya Nair
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Anamika Basu
- Copper Mountain College, Joshua Tree, CA 92252, USA
- Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
| | - Taslim A. Al-Hilal
- Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Texas at El Paso, El Paso, TX 79968, USA
| | - Sourav Roy
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA
- Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
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Lu J, Zhu D, Li L. Biological Functions and Molecular Mechanisms of MiR-608 in Cancer. Front Oncol 2022; 12:870983. [PMID: 35387124 PMCID: PMC8977622 DOI: 10.3389/fonc.2022.870983] [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: 02/07/2022] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
In recent years, microRNAs (miRNAs) have attracted much attention because of their prominent role in cancer. An increasing number of studies have shown that miRNAs play an important role in a variety of tumors. miR-608 has been reported to be decreased in cancers, especially in solid tumors. miR-608 is regarded as a tumor suppressor, which has been verified through a large number of experiments both in vivo and in vitro. miR-608 participates in many biological processes, including cell proliferation, invasion, migration, and apoptosis, by inhibiting transmembrane proteins and many signaling pathways. Here, we summarize the expression profile and biological functions and mechanism of miR-608, suggesting that miR-608 is an ideal diagnostic and prognostic biomarker and a treatment target for cancer.
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Affiliation(s)
- Juan Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Danhua Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Radanova M, Levkova M, Mihaylova G, Manev R, Maneva M, Hadgiev R, Conev N, Donev I. Single Nucleotide Polymorphisms in microRNA Genes and Colorectal Cancer Risk and Prognosis. Biomedicines 2022; 10:156. [PMID: 35052835 PMCID: PMC8773793 DOI: 10.3390/biomedicines10010156] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/09/2022] [Accepted: 01/10/2022] [Indexed: 02/01/2023] Open
Abstract
There is growing interest in single nucleotide polymorphisms (SNPs) in the genes of microRNAs (miRNAs), which could be associated with susceptibility to colorectal cancer (CRC) and therefore for prognosis of the disease and/or treatment response. Moreover, these miRNAs-SNPs could serve as new, low-invasive biomarkers for early detection of CRC. In the present article, we performed a thorough review of different SNPs, which were investigated for a correlation with the CRC risk, prognosis, and treatment response. We also analyzed the results from different meta-analyses and the possible reasons for reported contradictory findings, especially when different research groups investigated the same SNP in a gene for a particular miRNA. This illustrates the need for more case-control studies involving participants with different ethnic backgrounds. According to our review, three miRNAs-SNPs-miR-146a rs2910164, miR-27a rs895819 and miR-608 rs4919510-appear as promising prognostic, diagnostic and predictive biomarkers for CRC, respectively.
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Affiliation(s)
- Maria Radanova
- Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, 9000 Varna, Bulgaria;
- Laboratory of Molecular Pathology, University Hospital “St. Marina”, 9000 Varna, Bulgaria
| | - Mariya Levkova
- Department of Medical Genetics, Medical University of Varna, 9000 Varna, Bulgaria;
| | - Galya Mihaylova
- Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, 9000 Varna, Bulgaria;
| | - Rostislav Manev
- Department of Oncology, Medical University of Varna, 9000 Varna, Bulgaria; (R.M.); (M.M.); (N.C.)
- Clinic of Medical Oncology, University Hospital “St. Marina”, 9000 Varna, Bulgaria
| | - Margarita Maneva
- Department of Oncology, Medical University of Varna, 9000 Varna, Bulgaria; (R.M.); (M.M.); (N.C.)
- Clinic of Medical Oncology, University Hospital “St. Marina”, 9000 Varna, Bulgaria
| | - Rossen Hadgiev
- Department of Anatomy and Histology, Pathology and Forensic Medicine, Sofia University “St. Kliment Ohridski”, 1000 Sofia, Bulgaria;
| | - Nikolay Conev
- Department of Oncology, Medical University of Varna, 9000 Varna, Bulgaria; (R.M.); (M.M.); (N.C.)
- Clinic of Medical Oncology, University Hospital “St. Marina”, 9000 Varna, Bulgaria
| | - Ivan Donev
- Clinic of Medical Oncology, Hospital “Nadezhda”, 1000 Sofia, Bulgaria;
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8
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Morales-Pison S, Jara L, Carrasco V, Gutiérrez-Vera C, Reyes JM, Gonzalez-Hormazabal P, Carreño LJ, Tapia JC, Contreras HR. Genetic Variation in MicroRNA-423 Promotes Proliferation, Migration, Invasion, and Chemoresistance in Breast Cancer Cells. Int J Mol Sci 2021; 23:ijms23010380. [PMID: 35008806 PMCID: PMC8745459 DOI: 10.3390/ijms23010380] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/23/2021] [Accepted: 12/27/2021] [Indexed: 12/11/2022] Open
Abstract
MicroRNA-423 (miR-423) is highly expressed in breast cancer (BC). Previously, our group showed that the SNP rs6505162:C>A located in the pre-miR-423 was significantly associated with increased familial BC risk in patients with a strong family history of BC. Therefore, in this study, we evaluated the functional role of rs6505162 in mammary tumorigenesis in vitro to corroborate the association of this SNP with BC risk. We found that rs6505162:C>A upregulated expression of both mature miR-423 sequences (3p and 5p). Moreover, pre-miR-423-A enhanced proliferation, and promoted cisplatin resistance in BC cell lines. We also showed that pre-miR-423-A expression decreased cisplatin-induced apoptosis, and increased BC cell migration and invasion. We propose that the rs6505162-A allele promotes miR-423 overexpression, and that the rs6505162-A allele induces BC cell proliferation, viability, chemoresistance, migration, and invasion, and decreases cell apoptosis as a consequence. We suggest that rs6505162:C>A is a functional SNP site with potential utility as a marker for early diagnosis, prognosis, and treatment efficacy monitoring in BRCA1/2-negative BC patients, as well as a possible therapeutic target.
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Affiliation(s)
- Sebastian Morales-Pison
- Laboratorio de Genética Humana, Programa de Genética Humana, Instituto de Ciencia Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (S.M.-P.); (L.J.); (P.G.-H.)
| | - Lilian Jara
- Laboratorio de Genética Humana, Programa de Genética Humana, Instituto de Ciencia Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (S.M.-P.); (L.J.); (P.G.-H.)
| | - Valentina Carrasco
- Laboratorio de Biología Estructural y Molecular, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago 8380453, Chile;
| | - Cristian Gutiérrez-Vera
- Millennium Institute on Immunology and Immunotherapy, Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (C.G.-V.); (L.J.C.)
| | | | - Patricio Gonzalez-Hormazabal
- Laboratorio de Genética Humana, Programa de Genética Humana, Instituto de Ciencia Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (S.M.-P.); (L.J.); (P.G.-H.)
| | - Leandro J. Carreño
- Millennium Institute on Immunology and Immunotherapy, Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile; (C.G.-V.); (L.J.C.)
| | - Julio C. Tapia
- Laboratorio de Transformación Celular, Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
- Correspondence: (J.C.T.); (H.R.C.); Tel.: +56-2-9788647 (J.C.T.)
| | - Héctor R. Contreras
- Laboratorio de Biología Celular y Molecular, Departamento de Oncología Básico Clínica, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
- Correspondence: (J.C.T.); (H.R.C.); Tel.: +56-2-9788647 (J.C.T.)
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Moazzendizaji S, Sevbitov A, Ezzatifar F, Jalili HR, Aalii M, Hemmatzadeh M, Aslani S, Gholizadeh Navashenaq J, Safari R, Hosseinzadeh R, Rahmany MR, Mohammadi H. microRNAs: Small molecules with a large impact on colorectal cancer. Biotechnol Appl Biochem 2021; 69:1893-1908. [PMID: 34550619 DOI: 10.1002/bab.2255] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/03/2021] [Indexed: 12/23/2022]
Abstract
Colorectal cancer (CRC) accounts for one of the main cancer-related mortality and morbidity worldwide. The molecular mechanisms of CRC development have been broadly investigated and, over the last decade, it has become evident that aberrant transcription of microRNAs (miRNAs), a class of small, noncoding RNA molecules, has a significant role in the inception and promotion of CRC. In the involved tissues of CRC, the transcription profile of miRNAs is modulated, and their expression templates are related with prognosis, diagnosis, and treatment outcomes. Here, in the current review, we attempted to discuss the latest information regarding the aberrantly expressed miRNAs in CRC and the advantages of utilizing miRNAs as biomarkers for early diagnosis and prognosis of CRC as well as potential therapeutic application. The effect of miRNAs involved in various signaling pathways, primarily p53, EGFR, Wnt, and TGF-β pathways, was clarified.
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Affiliation(s)
- Sahand Moazzendizaji
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Andrey Sevbitov
- Head of Department of Propaedeutics of Dental Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Fatemeh Ezzatifar
- Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.,Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hamid Reza Jalili
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Morteza Aalii
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Maryam Hemmatzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeed Aslani
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Roghaiyeh Safari
- Molecular and Cellular Epigenetics (GIGA), University of Liege, Sart-Tilman Liège, Belgium.,13. Molecular and Cellular Biology (TERRA), Gembloux Agro-Bio Tech, University of Liege, Gembloux, Belgium
| | - Ramin Hosseinzadeh
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Rahmany
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Hamed Mohammadi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.,Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
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Hashemi M, Bizhani F, Danesh H, Narouie B, Sotoudeh M, Radfar MH, Ramezani MH, Bahari G, Taheri M, Ghavami S. MiR-608 rs4919510 C > G polymorphism increased the risk of bladder cancer in an Iranian population. AIMS GENETICS 2021. [DOI: 10.3934/genet.2016.4.212] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Abstract
MicroRNAs (miRNAs) participate in diverse biological pathways and may act as oncogenes or tumor suppressors. The single nucleotide polymorphisms (SNPs) in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C > G variant on bladder cancer risk. This case-control study conducted on 233 bladder cancer patients and 252 healthy subjects. Genotyping of miR-608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings showed that CG as well as CG + GG genotypes significantly increased the risk of bladder cancer (OR = 1.94, 95% CI = 1.28–2.94, p = 0.002, and OR = 1.90, 95% CI = 1.26–2.86, p = 0.002, respectively) compared to CC genotype. The G allele significantly increased the risk of bladder cancer compared to C allele (OR = 1.69, 95% CI = 1.17–2.45, p = 0.005). Our findings proposed that miR-608 polymorphism might be associated with increased risk of bladder cancer in a sample of Iranian population. Further large-scale studies with different ethnicities are needed to verify our findings.
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Affiliation(s)
- Mohammad Hashemi
- Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Fatemeh Bizhani
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Hiva Danesh
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Behzad Narouie
- Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
- Urology and Nephrology Research Center; Department of Urology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Sotoudeh
- Urology and Nephrology Research Center; Department of Urology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hadi Radfar
- Urology and Nephrology Research Center; Department of Urology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Honarkar Ramezani
- Urology and Nephrology Research Center; Department of Urology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gholamreza Bahari
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohsen Taheri
- Genetic of non-communicable disease research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Saeid Ghavami
- Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
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11
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Chen M, Cai D, Gu H, Yang J, Fan L. MALAT1 rs619586 A/G polymorphisms are associated with decreased risk of lung cancer. Medicine (Baltimore) 2021; 100:e23716. [PMID: 33761627 PMCID: PMC9281991 DOI: 10.1097/md.0000000000023716] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 11/16/2020] [Indexed: 01/05/2023] Open
Abstract
Lung cancer is the leading cause of cancer-associated mortality worldwide. Genetic factors are reported to play important roles in lung carcinogenesis. To evaluate genetic susceptibility, we conducted a hospital-based case-control study on the effects of functional single nucleotide polymorphisms (SNPs) in long non-coding RNAs (lncRNAs) and microRNAs on lung cancer development. A total of 917 lung cancer cases and 925 control subjects were recruited. The MALAT1 rs619586 A/G genotype frequencies between patient and control groups were significantly different (P < .001), specifically, 83.85% vs 75.88% (AA), 15.60% vs 21.79% (AG), and 0.55% vs 2.32% (GG). When the homozygous genotype MALAT1 rs619586 AA was used as the reference group, AG (AG vs AA: adjusted odds ratio [OR] 0.65, 95% confidential interval [CI] 0.51-0.83, P = .001) and GG genotypes were associated with significantly decreased risk of lung cancer (GG vs AA: adjusted OR 0.22, 95% CI 0.08-0.59, P = .003). In the dominant model, MALAT1 rs619586 AG/GG variants were also associated with a significantly decreased risk of lung cancer (adjusted OR 0.61, 95% CI 0.48-0.78, P < .001). In the recessive model, when MALAT1 rs619586 AA/AG genotypes were used as the reference group, the GG homozygous genotype was also associated with significantly decreased risk for lung cancer (adjusted OR 0.24, 95% CI 0.09-0.64, P = .004). Hsa-miR-34b/c rs4938723 T > C, pri-miR-124-1 rs531564 C > G and hsa-miR-423 rs6505162 C > A SNPs were not associated with lung cancer risk. Our collective data indicated that MALAT1 rs619586 A/G SNPs significantly reduced the risk of lung cancer. Large-scale studies on different ethnic populations and tissue-specific biological characterization are required to validate the current findings.
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Affiliation(s)
- Ming Chen
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Deng Cai
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Haiyong Gu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jun Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Liming Fan
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
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12
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Aghabozorgi AS, Sharif S, Jafarzadeh-Esfehani R, Vakili S, Abbaszadegan MR. Role of miRNA gene variants in the susceptibility and pharmacogenetics of colorectal cancer. Pharmacogenomics 2021; 22:303-318. [PMID: 33733820 DOI: 10.2217/pgs-2020-0159] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most significant challenges in the field of cancer pathology. miRNAs are among the genetic factors associated with the disease. Although many studies have reviewed the expression patterns of various miRNAs in CRC, few studies have focused on different variants of miRNA. In the present review, miRNA variants have been categorized into three subgroups, including miRNA variants that predict susceptibility to CRC, miRNA variants that predict the clinical parameters of CRC and finally, miRNA variants that predict the pharmacological aspects of CRC. Moreover, a comprehensive review of potentially functional miRNA-associated SNPs as well as their importance as candidate cancer biomarkers are discussed.
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Affiliation(s)
| | - Samaneh Sharif
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Saba Vakili
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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13
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Ke R, Lv L, Zhang S, Zhang F, Jiang Y. Functional mechanism and clinical implications of MicroRNA-423 in human cancers. Cancer Med 2020; 9:9036-9051. [PMID: 33174687 PMCID: PMC7724490 DOI: 10.1002/cam4.3557] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 08/16/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs play a vital role in the regulatory mechanisms of tumorigenesis. Current research indicates that microRNA-423 (miR-423) is abnormally expressed in various human tumors and participates in multiple signaling pathways of cancer progression. In most studies, miR-423 was confirmed as oncomiR, while a few contradictory reports considered miR-423 as an anticancer miRNA. The paradoxical role in cancer may hinder the application of miR-423 as a diagnostic and therapeutic target. Simultaneously, the interaction mechanism between miR-423 and lncRNA also needs attention. In this review, we have summarized the dual role of aberrant miR-423 expression and its mechanisms in tumorigenesis, and the therapeutic potential of miR-423 in human tumors.
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Affiliation(s)
- RuiSheng Ke
- Department of General Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China.,The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou City, China
| | - LiZhi Lv
- The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou City, China.,Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, Fuzhou City, China
| | - SiYu Zhang
- Department of General Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - FuXing Zhang
- Department of General Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Yi Jiang
- The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou City, China.,Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, Fuzhou City, China
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14
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Zhu X, Liu Y, Xu J, Cheng Z, Yu Y, Chu M, Lu X, Yuan W. miR-608 rs4919510 Polymorphism May Affect Susceptibility to Colorectal Cancer by Upregulating MRPL43 Expression. DNA Cell Biol 2020; 39:2017-2027. [PMID: 33147064 DOI: 10.1089/dna.2020.5689] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
There are many studies on the association between miR-608 rs4919510 polymorphism and susceptibility to colorectal cancer (CRC). However, the role of rs4919510 in CRC development and its underlying mechanism remain unclear. We first evaluated the gene that may be regulated by the variation of rs4919510 through a two-stage expression quantitative trait loci analysis and then compared the expression of that identified gene in CRC tissues and adjacent nontumor tissues. Next, methyl thiazolyl tetrazolium (MTT) assay, transwell assay, and flow cytometry analyses were performed to investigate the in vitro capacity of cell proliferation, migration, invasion, apoptosis, and cell cycle of CRC cells, respectively. Finally, through bioinformatics prediction, we contrasted the regulatory network and identified microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that could regulate the obtained gene. We found that the variant G allele of rs4919510 located in miR-608 was associated with a potentially increased expression of MRPL43 in colon tissues (p = 0.065). Moreover, the results of functional experiments suggested that knockdown of the MRPL43 gene could inhibit the growth of the CRC HCT-116 cell line and promote apoptosis. Additionally, the cell cycle of CRC HCT-116 cell line was significantly arrested at the G2 phase. Next, we obtained a competing endogenous RNA regulatory network of MRPL43 with 17 pairs of miRNAs-lncRNAs by bioinformatics prediction, out of which, survival analysis indicated that different expression levels of miR-193b-3p (p = 0.0269) and miR-194-3p (p = 0.0113) were associated with overall survival in CRC patients. The rs4919510 variant G allele in miR-608 may increase the proliferation, invasion, and migration ability and decrease the apoptosis of CRC HCT-116 cell line by upregulating the expression of MRPL43, ultimately may affect the risk of CRC. Moreover, miR-193b-3p and miR-194-3p that target MRPL43 may serve as potential predictive biomarkers of CRC survival.
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Affiliation(s)
- Xiaoqi Zhu
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
| | - Yichen Liu
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
| | - Jingsheng Xu
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
| | - Zhounan Cheng
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
| | - Yuhui Yu
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
| | - Minjie Chu
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
| | - Xiao Lu
- Department of Oncology, Changshu No. 1 People's Hospital, Suzhou, China
| | - Weiyan Yuan
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China
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15
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Raad M, Bayat A, Sharafshah A, Amiri AZ, Zohour MM, Ahmadvand M. Association and in silico investigations of miR-302c insertion/deletion variant as a novel biomarker with susceptibility to gastric cancer. J Cell Biochem 2019; 120:18946-18955. [PMID: 31219213 DOI: 10.1002/jcb.29215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 06/04/2019] [Indexed: 11/07/2022]
Abstract
Gastric cancer (GC) is the fifth most prevalent malignant tumor and the third most frequent cause of cancer mortality worldwide. rs199971565 is an insertion/deletion (INDEL) located in microRNA-302c (miR-302c) seed site, which may affect its function and biogenesis. There is no genetic association study investigating this INDEL with any disease till now. Thus, the current study was conducted to investigate the association of rs199971565 with susceptibility to GC in an Iranian population. In addition, in silico studies were performed to reveal the possible functional significance of this INDEL. A total of 378 subjects were genotyped through amplification refractory mutation system PCR (ARMS-PCR) after DNA extraction from peripheral blood by the salting out procedure. Also, in silico analyses were performed through databases and web tools including MiRNASNP V2.0, miRWalk V2.0, miRTarBase, DAVID V6.8, RNAfold, PHDcleave, miRmap, and STarMir. Results revealed that there was an association between rs199971565 and the incidence risk of GC under a recessive (P = .04, odds ratio [OR] = 18.73; 95% confidence interval [CI] = 1.07-326.95) model of inheritance. Also, compared to the Ins allele, the Del allele significantly increased the risk of GC (P = .01, OR = 2.02; 95% CI = 1.11-3.66). Further analyses showed no significant association in age and sex between two study groups (P = .216 and P = .798, respectively). In conclusion, for the first time, this study indicated the association and in silico investigations of rs199971565 and suggested it as a novel INDEL biomarker located in the seed site of miR-302c, which may have crucial roles in the susceptibility to GC and its incidence risk.
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Affiliation(s)
- Mohammad Raad
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
| | - Amir Bayat
- Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Sharafshah
- Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Zahedi Amiri
- Manitoba Centre for Proteomics and Systems Biology, John Buhler Research Centre, Winnipeg, Canada
| | - Mostafa Montazer Zohour
- Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohammad Ahmadvand
- Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
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16
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Wang Y, Lu Z, Fu L, Tan Y, Che D, Huang P, Pi L, Xu Y, Liang Q, Zhang L, Qiu X, Gu X. The miRNA-608 rs4919510 G>C polymorphism confers reduce coronary injury of Kawasaki disease in a Southern Chinese population. Biosci Rep 2019; 39:BSR20181660. [PMID: 31043452 PMCID: PMC6522709 DOI: 10.1042/bsr20181660] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 04/16/2019] [Accepted: 04/29/2019] [Indexed: 12/19/2022] Open
Abstract
Kawasaki disease (KD) is also called mucocutaneous lymph node syndrome and is an acute febrile pediatric disease characterized by systemic vasculitis. KD typically occurs in children 5 years old or younger and occurs more often in males than in females. miRNA-608 has been reported to interact with interleukin-6 and affect innate immunity. The immune-mediated inflammation could induce the occurrence of KD; however, there is no previous research focused on the relationship between miRNA-608 polymorphism and the KD risk. The present study explored the correlation between the miRNA-608 rs4919510 G>C polymorphism and the risk for KD. We recruited 532 patients with KD and 623 controls to genotype the miRNA-608 rs4919510 G>C polymorphism with a TaqMan allelic discrimination assay. Single-locus analysis showed no significant association between miRNA rs4919510 G>C polymorphism and KD susceptibility. However in an analysis stratified by age, gender, and coronary artery lesion (CAL), we found a relationship between the miRNA-608 rs4919510 G>C polymorphism and KD susceptibility. When KD patients were stratified by coronary injury, the CG/CC genotypes of the miRNA-608 rs4919510 G>C polymorphism contributed to a higher occurrence of KD than that was found in the GG genotype patients (adjusted odds ratio = 0.74, 95% CI = 0.56-0.98, P = 0.033). The present study demonstrated that the miRNA-608 rs4919510 G>C polymorphism may have a CAL-related relationship with KD susceptibility that has not been previously revealed.
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Affiliation(s)
- Yanfei Wang
- Department of Cardiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Zhaoliang Lu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Lanyan Fu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Yaqian Tan
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Di Che
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Ping Huang
- Department of Cardiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Lei Pi
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Yufen Xu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Qihua Liang
- Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Li Zhang
- Department of Cardiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Xiantao Qiu
- Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Xiaoqiong Gu
- Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
- Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
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17
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Ding HX, Lv Z, Yuan Y, Xu Q. MiRNA Polymorphisms and Cancer Prognosis: A Systematic Review and Meta-Analysis. Front Oncol 2018; 8:596. [PMID: 30619739 PMCID: PMC6300499 DOI: 10.3389/fonc.2018.00596] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 11/26/2018] [Indexed: 12/19/2022] Open
Abstract
Background: Accumulating studies have focused on the relationship between miRNAs polymorphisms and cancer prognosis. However, the results are conflicting and unconvincing. This systematic review and meta-analysis was conducted to explore the relationship between miRNAs polymorphisms and cancer prognosis, aiming to seek for markers with cancer prognostic function. Methods: Hazard ratio of overall survival, disease-free survival (DFS) and recurrence-free survival were calculated to evaluate the association between miRNAs polymorphisms and cancer prognosis by using Stata software 11.0. Results: We systematically reviewed the association of 17 miRNAs SNPs with cancer prognosis including 24,721 samples. It was shown that 6 miRNAs SNPs (miR-608 rs4919510, miR-492 rs2289030, miR-378 rs1076064, miR-499 rs4919510, miR-149 rs2292832, miR-196a2 rs11614913) were associated with better cancer overall survival (OS) while let-7i rs10877887 was associated with poor OS; the homozygous and heterozygote genotype of miR-423 were related to poor cancer relapse-free survival (RFS) when compared with the wild genotype; miR-146 rs2910164 was linked to favorable cancer DFS while miR-196a2 rs11614913 was associated with poor DFS. Conclusions: In summary, let-7i rs10877887, miR-608 rs4919510, miR-492 rs2289030, miR-378 rs1076064, miR-423 rs6505162, miR-499 rs4919510, miR-149 rs2292832, miR-146 rs2910164, and miR-196a2 rs11614913 might serve as potential biomarkers for cancer prognosis.
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Affiliation(s)
- Han-Xi Ding
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| | - Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
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18
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Mir R, Al Balawi IA, Duhier FMA. Involvement of microRNA-423 Gene Variability in Breast Cancer Progression in Saudi Arabia. Asian Pac J Cancer Prev 2018; 19:2581-2589. [PMID: 30256064 PMCID: PMC6249472 DOI: 10.22034/apjcp.2018.19.9.2581] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Aim: microRNA-423 is an oncogenic factor which is frequently upregulated in cancer. However, associations with breast cancer risk remain inconsistent. Therefore, we investigated the prevalence of microRNA-423 rs6505162C>T gene variation with breast cancer susceptibility in Saudi women. Methodology: This study was conducted on 100 breast cancer patients and 124 matched healthy individuals. Genotyping of the microRNA-423 rs6505162C/T gene variation was performed by using the amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution between the breast cancer cases and controls (p=0.0001), the frequencies of the genotypes CC,CT and TT being 25%, 52% and 23% in patients and 65%,20% and 15% respectively, in controls. The microRNA-423 C>T variant was associated with an increased risk of breast cancer in codominant models for (OR = 6.73, 95 % CI, 3.50-12.97; RR 2.35(1.67-3.30, p=0.0001) the microRNA-423TT genotype and (OR = 4.14, 95 % CI, 1.93-8.87; p=0.0003) microRNA-423CT (OR= 6.73, 95% CI, 3.50-12.97; p=0.0001) and also with the dominant model (OR 5.6(3.14-1.01), p=0.0001) CT+TT vs CC) with a non-significant association for the recessive model (OR=1.75, 95%CI=0.08-3.44, P=0.139, TT vs CC+CT). The T allele significantly increased the risk of breast cancer (OR =2.63, 95 % CI, 1.77-3.91; p=0.001) compared to the C allele. Some 6.73 ,4.14 and 2.63 fold increased risk of developing breast cancer was associated with TT and CT genotypes and the T allele of microRNA-423 in the northwestern region of Saudi Arabia. Conclusion: Our findings indicate that the microRNA-423 TT genotype and the T allele are associated with an increased susceptibility, metastasis and advanced stage of breast cancer in Saudi Arabian patients. Further studies with larger sample sizes are necessary to confirm our findings.
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Affiliation(s)
- R Mir
- Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair, Faculty of Applied Medical Sciences,University of Tabuk, Tabuk, Kingdom of Saudi Arabia.
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Alidoust M, Hamzehzadeh L, Rivandi M, Pasdar A. Polymorphisms in non-coding RNAs and risk of colorectal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol 2018; 132:100-110. [PMID: 30447914 DOI: 10.1016/j.critrevonc.2018.09.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 07/23/2018] [Accepted: 09/05/2018] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) has been regarded as a common cancer due to its prevailing incidence in both males and females. Recently, non-coding RNAs used as biomarkers for screening, diagnosis and prognosis of different cancers have been under the focus of attention. As a result of this, the aim of this study was to systematically review articles that investigated the SNPs in genes related to microRNAs and long non-coding RNAs to assess the genetic susceptibility of colorectal cancer risk. The outcome is presented as the results of a meta-analysis. We systematically searched PubMed, Web of Science, and Scopus to identify relevant studies published up to 20/5/2017. These included eligible studies consisting of 23,581 patients and 22,697 controls. The conferred risk was estimated and presented using odds ratios (ORs) and 95% confidence intervals (CI). The Hardy-Weinberg equilibrium (HWE) was assessed by the goodness-of-fit chi-square test in all studies. The power of each study was also calculated based on the available results. Out of 27 different microRNAs which had published results, although most of the studies were under powered, miR-146a and miR-196a were amongst the most studied microRNAs. For five miRNAs (miR-196a, miR-146a, miR-27a, miR-499 and miR-149) which we performed a meta-analysis, miR-27a and miR-149 gene polymorphisms were associated with susceptibility to CRC. Other miRNAs did not show any effect on the CRC risk. Overall, significant association between miR-149 rs2292832 and susceptibility to cancer was identified in a recessive genetic model, TT/ (TC + CC) (OR = 1.19, 95% CI = 1.02-1.39, P = 0.02). On the other hand, rs895819 (miR-27a) GG carriers were more susceptible to CRC (OR = 1.47, 95% CI = 1.21-1.78, P = <0.05) in a recessive genetic model. Analysis of the data based on race revealed that rs2910164 (miR-146a) polymorphism may decrease the risk of CRC among Europeans, in a co dominant model [OR = 0.81, 95% CI 0.66-0.99, p = 0.04], but not among Asians. In conclusion, certain miRNAs (miR-27a and miR-149) may affect the CRC risk and can be regarded as genetic markers amongst different populations. LncRNAs still have to be studied more to reach a conclusion for their association with CRC risk.
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Affiliation(s)
- Maryam Alidoust
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Leila Hamzehzadeh
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdi Rivandi
- Medical Genetics Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Pasdar
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, UK.
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20
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Correlations of MicroRNA-21 Gene Polymorphisms With Chemosensitivity and Prognosis of Cervical Cancer. Am J Med Sci 2018; 356:544-551. [PMID: 30447706 DOI: 10.1016/j.amjms.2018.08.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 08/06/2018] [Accepted: 08/24/2018] [Indexed: 01/26/2023]
Abstract
BACKGROUND We investigated correlations of miR-21 gene polymorphisms including rs1292037 (A > G) and rs13137 (A > T) with the chemosensitivity to cisplatin plus paclitaxel, and prognosis before cervical cancer (CC) surgery, which may provide a novel target for prevention and treatment of CC. MATERIALS AND METHODS A total of 165 patients with CC were divided into 2 groups, a sensitive group and resistance group. Gene polymorphisms of rs1292037 (A > G) and rs13137 (A > T) were detected respectively. Logistic and Cox multivariate regression analyses were used to explore factors that influence resistance to cisplatin plus paclitaxel. RESULTS rs1292037 (A > G) locus AG, GG, AG + GG and G allele in miR-21 gene may increase chemoresistance to cisplatin plus paclitaxel in CC. The risk factors of prognosis included rs1292037 (A > G) locus, tumor stage, maximum lesion diameter and lymph node metastasis (hazard ratio [HR] = 1.819, 95% CI = 1.127-2.935; HR = 1.504, 95% CI = 1.070-2.114; HR = 1.671, 95% CI = 1.038-2.689; HR = 3.043, 95% CI = 1.783-5.193). The influencing factors of resistance to cisplatin plus paclitaxel included maximum lesion diameter, tumor stage, lymph node metastasis and rs1292037 (odds ratio [OR] = 14.047, 95% CI = 5.694-34.653; OR = 5.873, 95% CI = 3.104-11.110; OR = 3.574, 95% CI = 1.554-8.216; OR = 2.449, 95% CI = 1.052-5.705). CONCLUSIONS rs1292037 (A > G) locus are associated with the chemoresistance to cisplatin plus paclitaxel and prognosis of patients with CC. In addition to that, the G allele at rs1292037 (A > G) locus increases the risk of preoperative chemoresistance to cisplatin plus paclitaxel and is a poor prognostic factor for patients with CC.
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21
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Hahne JC, Valeri N. Non-Coding RNAs and Resistance to Anticancer Drugs in Gastrointestinal Tumors. Front Oncol 2018; 8:226. [PMID: 29967761 PMCID: PMC6015885 DOI: 10.3389/fonc.2018.00226] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 05/31/2018] [Indexed: 12/12/2022] Open
Abstract
Non-coding RNAs are important regulators of gene expression and transcription. It is well established that impaired non-coding RNA expression especially the one of long non-coding RNAs and microRNAs is involved in a number of pathological conditions including cancer. Non-coding RNAs are responsible for the development of resistance to anticancer treatments as they regulate drug resistance-related genes, affect intracellular drug concentrations, induce alternative signaling pathways, alter drug efficiency via blocking cell cycle regulation, and DNA damage response. Furthermore, they can prevent therapeutic-induced cell death and promote epithelial-mesenchymal transition (EMT) and elicit non-cell autonomous mechanisms of resistance. In this review, we summarize the role of non-coding RNAs for different mechanisms resulting in drug resistance (e.g., drug transport, drug metabolism, cell cycle regulation, regulation of apoptotic pathways, cancer stem cells, and EMT) in the context of gastrointestinal cancers.
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Affiliation(s)
- Jens C. Hahne
- Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom
| | - Nicola Valeri
- Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom
- Department of Medicine, The Royal Marsden NHS Trust, London, United Kingdom
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22
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Dai ZM, Lv JR, Liu K, Lei XM, Li W, Wu G, Liu XH, Zhu YX, Hao Q, Dai ZJ. The role of microRNA-608 polymorphism on the susceptibility and survival of cancer: a meta-analysis. Aging (Albany NY) 2018; 10:1402-1414. [PMID: 29909406 PMCID: PMC6046227 DOI: 10.18632/aging.101476] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 06/10/2018] [Indexed: 12/18/2022]
Abstract
The role of rs4919510 polymorphism in microRNA-608 (miR-608) and cancer susceptibility and prognosis remain controversial and debatable. We conducted a meta-analysis of twenty-four eligible publications on the association of rs4919510 polymorphism with cancer risk and/or prognosis. Odds ratios, hazard ratios, and 95% confidence interval were used to investigate the association between this polymorphism and susceptibility, overall survival, and recurrence-free survival of cancer. Overall, eighteen case-control studies and nine cohort studies evaluated the susceptibility and prognostic value of rs4919510 polymorphism in cancer, respectively. Pooled analysis showed that rs4919510 polymorphism was not associated with cancer risk in all five genetic models. When stratifying by different cancer sites, rs4919510 polymorphism was detected to have a significant association with a decreased risk of colorectal cancer in homozygous model (P = 0.006) and recessive model (P = 0.001), subgroup analysis also emerged a weakened correlation between rs4919510 polymorphism and an increased risk of papillary thyroid cancer in heterozygote model (P = 0.04). Furthermore, the prognosis of rs4919510 variant in cancer patients showed that rs4919510 GG genotype was significant association with poor recurrence-free survival in homozygous models (P = 0.04). The meta-analysis suggested that the microRNA-608 rs4919510 polymorphism maybe associate with a significantly decreased risk for colorectal cancer. Further investigations on larger populations are required to evaluate and confirm this relationship.
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Affiliation(s)
- Zhi-Ming Dai
- Department of Anesthesiology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
- Equal contribution
| | - Jian-Rui Lv
- Department of Anesthesiology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
- Equal contribution
| | - Kang Liu
- Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
- Equal contribution
| | - Xiao-Ming Lei
- Department of Anesthesiology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Wei Li
- Department of Anesthesiology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Gang Wu
- Department of Anesthesiology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Xing-Han Liu
- Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Yu-Xiao Zhu
- Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Qian Hao
- Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Zhi-Jun Dai
- Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
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23
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Yang PW, Huang PM, Yong LS, Chang YH, Wu CW, Hua KT, Hsieh MS, Lee JM. Circulating Interleukin-6 is Associated with Prognosis and Genetic Polymorphisms of MIR608 in Patients with Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2018; 25:2449-2456. [DOI: 10.1245/s10434-018-6532-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Indexed: 12/12/2022]
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24
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Jia W, Zeng L, Luo S, Bai F, Zhong R, Wu L, Huang GL, Pu X. Association of microRNA-423 rs6505162 C>A polymorphism with susceptibility and metastasis of colorectal carcinoma. Medicine (Baltimore) 2018; 97:e9846. [PMID: 29419695 PMCID: PMC5944659 DOI: 10.1097/md.0000000000009846] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Studies have evaluated the association between the SNP miRNA-423 rs6505162 C>A and cancer risk in several cancers with contradictory outcomes. It was reported that miRNA-423 rs6505162 C>A polymorphism was associated with the overall survival and the recurrence-free survival of colorectal carcinoma. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of colorectal carcinoma.In this study, we investigated the association between miRNA-423 polymorphism with risk and clinicopathological parameters of colorectal carcinoma. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype 117 colorectal carcinoma patients and 84 healthy controls.Our data indicated the frequencies of rs6505162 genotypes and alleles were significantly different between colorectal carcinoma patients and controls. Compared with CC homozygote, the AC heterozygote exhibited a significantly decreased risk of colorectal carcinoma; and the combination of AC and AA genotype was associated with decreased risk of colorectal carcinoma. The allele distribution of rs6505162 was significantly different between cases and controls. Furthermore, miR-423 rs6505162 C>A genotype showed a significant association with metastasis in patients (P = .022).Our study suggested that miR-423 rs6505162 C>A polymorphism was associated with the susceptibility and metastasis of colorectal carcinoma, and that miR-423 rs6505162 C>A polymorphism might be a potential biomarker for colorectal carcinoma.
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Affiliation(s)
- Wenrui Jia
- Department II of Chest Internal Medicine, Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha
- School of Laboratory Medicine, Guangdong Medical University, Dongguan
| | - Liuyan Zeng
- Department of Health Management Center, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China
- China-American Cancer Research Institute, Dongguan Scientific Research Center, Guangdong Medical University; Key Laboratory for Epigenetics of Dongguan City, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, China
| | - Shengqun Luo
- China-American Cancer Research Institute, Dongguan Scientific Research Center, Guangdong Medical University; Key Laboratory for Epigenetics of Dongguan City, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, China
| | - Fei Bai
- Department II of Chest Internal Medicine, Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha
| | - Rui Zhong
- Department II of Chest Internal Medicine, Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha
| | - Lin Wu
- Department II of Chest Internal Medicine, Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha
| | - Guo-Liang Huang
- China-American Cancer Research Institute, Dongguan Scientific Research Center, Guangdong Medical University; Key Laboratory for Epigenetics of Dongguan City, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, China
| | - Xingxiang Pu
- Department II of Chest Internal Medicine, Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha
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25
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Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy. Oncotarget 2018; 7:35015-25. [PMID: 27145460 PMCID: PMC5085206 DOI: 10.18632/oncotarget.9014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2016] [Accepted: 04/15/2016] [Indexed: 12/14/2022] Open
Abstract
Common single nucleotide polymorphisms (SNPs) in miRNAs may affect miRNA functions and their target expression and thus may affect biological activities and cancer etiology as well as prognosis. Thus, we determined whether the 9 SNPs in microRNAs modify the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. We found that the SNPs in the miRNA146, miRNA196, and Gemin3 were associated with a significantly reduced and increased risk of SCCOP recurrence after multivariate adjustment (aHR, 0.6, 95%CI, 0.4-0.9, aHR, 2.1, 95%CI, 1.6-2.8, and aHR, 0.6, 95%CI, 0.5-0.9, respectively). Furthermore, the similar effect of these 3 SNPs on SCCOP recurrence risk was found in HPV-positive SCCOP patients only. However, no significant associations were found for other SNPs. To evaluate the aggregate effects of these SNPs, we performed a combined risk genotype analysis. We found that, compared with the low-risk reference group with less than 4 risk genotypes, the medium-risk group with 4 or 5 risk genotypes exhibited a 1.7-fold (1.2-2.4) increased risk whereas the high-risk group with more than 5 risk genotypes exhibited a 3.0-fold (1.7-4.2) increased risk (Ptrend < 0.001). Such combined effects were particularly pronounced in HPV-positive SCCOP patients. Taken together, this is the first study with a large cohort of SCCOP patients showing that miRNA-related genetic variants may modify risk of SCCOP recurrence individually and jointly. Larger studies are needed to validate these results.
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26
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Vodicka P, Pardini B, Vymetalkova V, Naccarati A. Polymorphisms in Non-coding RNA Genes and Their Targets Sites as Risk Factors of Sporadic Colorectal Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 937:123-49. [PMID: 27573898 DOI: 10.1007/978-3-319-42059-2_7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors in interplay with epigenetic mechanisms, such as microRNAs (miRNAs). CRC cases are predominantly sporadic in which the disease develops with no apparent hereditary syndrome. The last decade has seen the progress of genome-wide association studies (GWAS) that allowed the discovery of several genetic regions and variants associated with weak effects on sporadic CRC. Collectively these variants may enable a more accurate prediction of an individual's risk to the disease and its prognosis. However, the number of variants contributing to CRC is still not fully explored.SNPs in genes encoding the miRNA sequence or in 3'UTR regions of the corresponding binding sites may affect miRNA transcription, miRNA processing, and/or the fidelity of the miRNA-mRNA interaction. These variants could plausibly impact miRNA expression and target mRNA translation into proteins critical for cellular integrity, differentiation, and proliferation.In the present chapter, we describe the different aspects of variations related to miRNAs and other non-coding RNAs (ncRNAs) and evidence from studies investigating these candidate genetic alterations in support to their role in CRC development and progression.
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Affiliation(s)
- Pavel Vodicka
- Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 00, Prague, Czech Republic. .,Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00, Prague, Czech Republic. .,Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, 323 00, Pilsen, Czech Republic.
| | - Barbara Pardini
- Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 00, Prague, Czech Republic.,Human Genetics Foundation - Torino (HuGeF), via Nizza 52, 10126, Turin, Italy
| | - Veronika Vymetalkova
- Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 00, Prague, Czech Republic.,Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 128 00, Prague, Czech Republic
| | - Alessio Naccarati
- Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 00, Prague, Czech Republic.,Human Genetics Foundation - Torino (HuGeF), via Nizza 52, 10126, Turin, Italy
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27
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MiR-146a rs2910164 polymorphism increases the risk of digestive system cancer: A meta-analysis. Clin Res Hepatol Gastroenterol 2017; 41:93-102. [PMID: 27477122 DOI: 10.1016/j.clinre.2016.06.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Accepted: 06/29/2016] [Indexed: 02/04/2023]
Abstract
AIM There is merging evidence suggesting that the miR-146a polymorphism might be associated with susceptibility to digestive system cancer. However, previous published studies have failed to achieve a definitive conclusion. To address this issue, an updated meta-analysis was performed. METHODS A comprehensive electronic search was conducted using the following source to identify the eligible studies: PubMed, Embase, China BioMedicine, the Cochrane Library, and Google Scholar. Odds ratios and its corresponding 95% confidence interval (CI) was used in the quantitative synthesis. RESULTS The database search identified 1344 eligible studies, of which 32 (comprising 12,541 cases and 15,925 controls) were included. The results indicate that the miR-146a rs2910164 polymorphism was significantly associated with increased risk of digestive system cancer in heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.30, P=0.02), and recessive model (GG vs. GC+CC: OR=1.11, 95% CI: 1.04-1.17, P=0.006). Subgroup analysis by cancer site revealed increased risk in gastric cancer above heterozygote comparison (GG vs. GC: OR=1.13, 95% CI: 1.02-1.25, P=0.02), and recessive model (GG vs. GC+CC: OR=1.15, 95% CI: 1.04-1.26, P=0.006). Similarly, increased cancer risk was observed in hepatocellular carcinoma when compared with homozygote comparison (GG vs. CC: OR=1.21, 95% CI: 1.04-1.42, P=0.02), heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.29, P=0.02), and dominant model (GG+GC vs. CC: OR=1.16, 95% CI: 1.04-1.29, P=0.009). When stratified by ethnicity and quality score, increased cancer risks were also observed among Asians, Caucasians and high quality studies subgroup. CONCLUSION The current study revealed that miR-146a G/C genetic polymorphism was more likely to be associated with digestive system cancer risk.
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28
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Association of Polymorphisms in three pri-miRNAs that Target Pepsinogen C with the Risk and Prognosis of Gastric Cancer. Sci Rep 2017; 7:39528. [PMID: 28067243 PMCID: PMC5220333 DOI: 10.1038/srep39528] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 11/23/2016] [Indexed: 12/13/2022] Open
Abstract
We aimed to explore the associations of polymorphisms in three microRNAs (miRNAs) (let-7e rs8111742, miR-365b rs121224 and miR-4795 rs1002765) that target PGC with the risk and prognosis of gastric cancer/atrophic gastritis. Sequenom’s MassArray was used to genotype the miRNA polymorphisms in 724 gastric cancer cases, 862 atrophic gastritis cases and 862 controls in a Chinese population. We found that let-7e rs8111742 and miR-4795 rs1002765 were associated with the risk of gastric cancer in the H. pylori-positive subgroup. MiR-365b rs121224 was associated with the risk of intestinal-type gastric cancer in the alcohol consumption subgroup. Intestinal-type gastric cancer patients at Borrmann stages III-IV who carry the miR-365b rs121224 GG genotype had better prognosis compared with those who carry the CG or CC genotypes. MiR-365b rs121224 was associated with Lauren typing and TNM staging, in which the distribution of GG genotype carriers in intestinal-type gastric cancer and the TNM stage I-II subgroup was higher than that of CG or CC genotypes, which contrasted with the distribution in diffuse-type gastric cancer or TNM III-IV groups. These findings suggested that the polymorphisms in these miRNAs might be biomarkers for gastric cancer risk and prognosis, especially for populations infected with Helicobacter pylori or who consume alcohol.
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29
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Lingzi X, Zhihua Y, Xuelian L, Yangwu R, Haibo Z, Yuxia Z, Baosen Z. Genetic variants in microRNAs predict non-small cell lung cancer prognosis in Chinese female population in a prospective cohort study. Oncotarget 2016; 7:83101-83114. [PMID: 27825117 PMCID: PMC5347756 DOI: 10.18632/oncotarget.13072] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Accepted: 10/17/2016] [Indexed: 12/13/2022] Open
Abstract
To investigate the prognostic effect of microRNA single nucleotide polymorphisms (SNP) on non-small cell lung cancer (NSCLC) patients, 658 female participants from northeast China were enrolled in our prospective cohort study and followed up from 2010 to 2015. C-containing genotypes of miR-149 rs2292832 were associated with better overall survival (OS). The joint effect of miR-149 and miR-196a2 and the joint effect of miR-149 and miR-608 were also observed in our study. To verify the function of miR-149 rs2292832, A549 cell lines were stably transfected with lenti-virus containing miR-149-C vector, miR-149-T vector and empty vector. Cells containing C allele assumed a higher expression level of miR-149, a decrease in cell growth and the sensitivity to anticancer drug when compared with cells containing T allele. The role of miR-149 playing in cancer prognosis may function through DNA topoisomerases 1 (TOP1) pathway, according to the results from luciferase reporter assays. In conclusion, miR-149 C allele may be a prognostic biomarker for better NSCLC OS.
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MESH Headings
- A549 Cells
- Antineoplastic Agents/pharmacology
- Asian People/genetics
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Non-Small-Cell Lung/ethnology
- Carcinoma, Non-Small-Cell Lung/genetics
- Carcinoma, Non-Small-Cell Lung/metabolism
- Carcinoma, Non-Small-Cell Lung/therapy
- Cell Proliferation/drug effects
- China
- Cisplatin/pharmacology
- DNA Topoisomerases, Type I/genetics
- DNA Topoisomerases, Type I/metabolism
- Dose-Response Relationship, Drug
- Female
- Genetic Association Studies
- Genetic Predisposition to Disease
- Humans
- Kaplan-Meier Estimate
- Lung Neoplasms/ethnology
- Lung Neoplasms/genetics
- Lung Neoplasms/metabolism
- Lung Neoplasms/therapy
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Middle Aged
- Phenotype
- Polymorphism, Single Nucleotide
- Prospective Studies
- Risk Factors
- Sex Factors
- Time Factors
- Transfection
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Affiliation(s)
- Xia Lingzi
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, Peoples R China
- Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Province Department of Education, Shenyang, Liaoning, 110122, Peoples R China
| | - Yin Zhihua
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, Peoples R China
- Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Province Department of Education, Shenyang, Liaoning, 110122, Peoples R China
| | - Li Xuelian
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, Peoples R China
- Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Province Department of Education, Shenyang, Liaoning, 110122, Peoples R China
| | - Ren Yangwu
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, Peoples R China
- Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Province Department of Education, Shenyang, Liaoning, 110122, Peoples R China
| | - Zhang Haibo
- Department of Radiotherapy, Shenyang North Hospital, Shenyang, Liaoning, 110001, Peoples R China
| | - Zhao Yuxia
- Department of Radiotherapy Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, Peoples R China
| | - Zhou Baosen
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, 110122, Peoples R China
- Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Province Department of Education, Shenyang, Liaoning, 110122, Peoples R China
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30
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Ying HQ, Peng HX, He BS, Pan YQ, Wang F, Sun HL, Liu X, Chen J, Lin K, Wang SK. MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals. Oncotarget 2016; 7:75865-75873. [PMID: 27713147 PMCID: PMC5342784 DOI: 10.18632/oncotarget.12422] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 09/25/2016] [Indexed: 01/22/2023] Open
Abstract
Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.
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Affiliation(s)
- Hou-Qun Ying
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Hong-Xin Peng
- Medical School of Southeast University, Nanjing 210009, Jiangsu, China
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Bang-Shun He
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Yu-Qin Pan
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Feng Wang
- Department of Clinical Laboratory, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Hui-Ling Sun
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Xian Liu
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Jie Chen
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Kang Lin
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
| | - Shu-Kui Wang
- Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
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31
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Sclafani F, Chau I, Cunningham D, Lampis A, Hahne JC, Ghidini M, Lote H, Zito D, Tabernero J, Glimelius B, Cervantes A, Begum R, De Castro DG, Wilson SH, Peckitt C, Eltahir Z, Wotherspoon A, Tait D, Brown G, Oates J, Braconi C, Valeri N. Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients. Carcinogenesis 2016; 37:852-7. [PMID: 27381831 PMCID: PMC5008250 DOI: 10.1093/carcin/bgw073] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 06/21/2016] [Accepted: 06/28/2016] [Indexed: 12/12/2022] Open
Abstract
Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14-1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52-3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome.
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Affiliation(s)
- Francesco Sclafani
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Ian Chau
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - David Cunningham
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Andrea Lampis
- Department of Molecular Pathology, The Institute of Cancer Research, Surrey SM2 5NG, UK
| | - Jens Claus Hahne
- Department of Molecular Pathology, The Institute of Cancer Research, Surrey SM2 5NG, UK
| | - Michele Ghidini
- Department of Molecular Pathology, The Institute of Cancer Research, Surrey SM2 5NG, UK
| | - Hazel Lote
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK, Department of Molecular Pathology, The Institute of Cancer Research, Surrey SM2 5NG, UK
| | - Domenico Zito
- Department of Molecular Pathology, The Institute of Cancer Research, Surrey SM2 5NG, UK
| | - Josep Tabernero
- Department of Medical Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona 08035, Spain
| | - Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, University of Uppsala, Uppsala 78751 85, Sweden
| | - Andres Cervantes
- Department of Haematology and Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia 46010, Spain and
| | - Ruwaida Begum
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | | | - Sanna Hulkki Wilson
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Clare Peckitt
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Zakaria Eltahir
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Andrew Wotherspoon
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Diana Tait
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Gina Brown
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Jacqueline Oates
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK
| | - Chiara Braconi
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK, Department of Cancer Therapeutics, The Institute of Cancer Research, Surrey SM2 5NG, UK
| | - Nicola Valeri
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK, Department of Molecular Pathology, The Institute of Cancer Research, Surrey SM2 5NG, UK,
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Ma XP, Yu G, Chen X, Xiao Q, Shi Z, Zhang LY, Chen H, Zhang P, Ding DL, Huang HX, Saiyin H, Chen TY, Lu PX, Wang NJ, Yu H, Conran C, Sun J, Zheng SL, Xu J, Yu L, Jiang DK. MiR-608 rs4919510 is associated with prognosis of hepatocellular carcinoma. Tumour Biol 2016; 37:9931-9942. [PMID: 26815502 DOI: 10.1007/s13277-016-4897-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 01/20/2016] [Indexed: 12/18/2022] Open
Abstract
Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) are considered potential markers for risk and prognosis of various cancers. In the current study, we aimed to determine whether miR-608 rs4919510 affected hepatocellular carcinoma (HCC) prognosis. We genotyped rs4919510 using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. Associations between rs4919510 and overall survival (OS) and demographic characteristics and clinical features were estimated using the Cox proportional hazards model. Results showed that HCC patients who carried the rs4919510 CC genotype had a significantly longer OS compared to those who carried the GG genotype (P = 0.013, hazard ratio [HR] = 0.600, 95 % confidence interval [CI] 0.402-0.897) and the CG + GG genotype (P = 0.033, HR = 0.681, 95 % CI 0.479-0.970) in univariate analysis. Similar results were obtained in multivariate analysis. Further stratification analysis indicated that rs4919510 was significantly associated with OS in patients who were satisfied with one of the following criteria: male gender, HbsAg-positive, α-fetoprotein (AFP)-positive, tumor size >5 cm, cirrhosis, solitary tumor, I + II pTNM stage, or no tumor capsule. Finally, a significantly higher frequency of rs4919510 CC genotype was observed in patients with cirrhosis (22.9 %, 55/240) than those without cirrhosis (14.0 %, 17/121) (P = 0.047). In conclusion, our results illustrated the potential role of miR-608 rs4919510 as a prognostic marker for HCC patients undergoing surgical resection of the tumor.
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Affiliation(s)
- Xiao-Pin Ma
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
| | - Guopeng Yu
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
- Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
- Center for genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China
- Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China
- Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
- Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Xubo Chen
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
| | - Qianyi Xiao
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China
| | - Zhuqing Shi
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
- Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
- Center for genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China
| | - Lu-Yao Zhang
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
| | - Haitao Chen
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
- Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
- Center for genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China
| | - Pengyin Zhang
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
- Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
- Center for genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China
| | - Dong-Lin Ding
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
| | - Hui-Xing Huang
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
| | - Hexige Saiyin
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
| | - Tao-Yang Chen
- Qidong Liver Cancer Institute, Qidong People's Hospital, Qidong, Jiangsu, China
| | - Pei-Xin Lu
- Qidong Liver Cancer Institute, Qidong People's Hospital, Qidong, Jiangsu, China
| | - Neng-Jin Wang
- Qidong Liver Cancer Institute, Qidong People's Hospital, Qidong, Jiangsu, China
| | - Hongjie Yu
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
- Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
- Center for genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China
| | - Carly Conran
- Center for Genomic Cancer Research, NorthShore University HealthSystem, Evanston, IL, USA
| | - Jielin Sun
- Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - S Lilly Zheng
- Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
- Center for Genomic Cancer Research, NorthShore University HealthSystem, Evanston, IL, USA
| | - Jianfeng Xu
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
- Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
- Center for genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China
- Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China
- Center for Genomic Cancer Research, NorthShore University HealthSystem, Evanston, IL, USA
| | - Long Yu
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China
- Institute of Biomedical Science, Fudan University, Shanghai, China
| | - De-Ke Jiang
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Rd., Shanghai, 200438, China.
- Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
- Center for genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China.
- Center for Genetic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China.
- Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
- Center for Genomic Cancer Research, NorthShore University HealthSystem, Evanston, IL, USA.
- Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
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Kasar S, Underbayev C, Hassan M, Ilev I, Degheidy H, Bauer S, Marti G, Lutz C, Raveche E, Batish M. Alterations in the mir-15a/16-1 Loci Impairs Its Processing and Augments B-1 Expansion in De Novo Mouse Model of Chronic Lymphocytic Leukemia (CLL). PLoS One 2016; 11:e0149331. [PMID: 26959643 PMCID: PMC4784815 DOI: 10.1371/journal.pone.0149331] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 01/29/2016] [Indexed: 12/26/2022] Open
Abstract
New Zealand Black (NZB) mice, a de novo model of CLL, share multiple characteristics with CLL patients, including decreased expression of miR-15a/16-1. We previously discovered a point mutation and deletion in the 3' flanking region of mir-16-1 of NZB and a similar mutation has been found in a small number of CLL patients. However, it was unknown whether the mutation is the cause for the reduced miR-15a/16-1 expression and CLL development. Using PCR and in vitro microRNA processing assays, we found that the NZB sequence alterations in the mir-15a/16-1 loci result in deficient processing of the precursor forms of miR-15a/16-1, in particular, we observe impaired conversion of pri-miR-15a/16-1 to pre-miR-15a/16-1. The in vitro data was further supported by derivation of congenic strains with replaced mir-15a/16-1 loci at one or both alleles: NZB congenic mice (NmiR+/-) and DBA congenic mice (DmiR-/-). The level of miR-15a/16-1 reflected the configuration of the mir-15a/16-1 loci with DBA congenic mice (DmiR-/-) showing reduced miR-15a levels compared to homozygous wild-type allele, while the NZB congenic mice (NmiR+/-) showed an increase in miR-15a levels relative to homozygous mutant allele. Similar to Monoclonal B-cell Lymphocytosis (MBL), the precursor stage of the human disease, an overall expansion of the B-1 population was observed in DBA congenic mice (DmiR-/-) relative to wild-type (DmiR+/+). These studies support our hypothesis that the mutations in the mir-15a/16-1 loci are responsible for decreased expression of this regulatory microRNA leading to B-1 expansion and CLL development.
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Affiliation(s)
- Siddha Kasar
- New Jersey Medical School, Rutgers University, Newark, New Jersey, 07103, United States of America
| | - Chingiz Underbayev
- New Jersey Medical School, Rutgers University, Newark, New Jersey, 07103, United States of America
| | | | - Ilko Ilev
- OSEL/CDRH/FDA White Oak, Maryland, United States of America
| | - Heba Degheidy
- CBER/FDA White Oak, Maryland, United States of America
| | - Steven Bauer
- CBER/FDA White Oak, Maryland, United States of America
| | - Gerald Marti
- OSEL/CDRH/FDA White Oak, Maryland, United States of America
| | - Carol Lutz
- New Jersey Medical School, Rutgers University, Newark, New Jersey, 07103, United States of America
| | - Elizabeth Raveche
- New Jersey Medical School, Rutgers University, Newark, New Jersey, 07103, United States of America
| | - Mona Batish
- New Jersey Medical School, Rutgers University, Newark, New Jersey, 07103, United States of America
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Association between ERBB4 gene polymorphism in the microRNA binding site and endometrial carcinoma risk. Genes Genomics 2015. [DOI: 10.1007/s13258-015-0336-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Thomas J, Ohtsuka M, Pichler M, Ling H. MicroRNAs: Clinical Relevance in Colorectal Cancer. Int J Mol Sci 2015; 16:28063-76. [PMID: 26602923 PMCID: PMC4691027 DOI: 10.3390/ijms161226080] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 10/27/2015] [Accepted: 11/13/2015] [Indexed: 12/27/2022] Open
Abstract
Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer.
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Affiliation(s)
- Joe Thomas
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
| | - Masahisa Ohtsuka
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
| | - Martin Pichler
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
- Division of Oncology, Medical University of Graz, 8010 Graz, Austria.
| | - Hui Ling
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
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Ragusa M, Barbagallo C, Statello L, Condorelli AG, Battaglia R, Tamburello L, Barbagallo D, Di Pietro C, Purrello M. Non-coding landscapes of colorectal cancer. World J Gastroenterol 2015; 21:11709-11739. [PMID: 26556998 PMCID: PMC4631972 DOI: 10.3748/wjg.v21.i41.11709] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 07/28/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
For two decades Vogelstein’s model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy.
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Pipan V, Zorc M, Kunej T. MicroRNA Polymorphisms in Cancer: A Literature Analysis. Cancers (Basel) 2015; 7:1806-14. [PMID: 26371044 PMCID: PMC4586796 DOI: 10.3390/cancers7030863] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 08/26/2015] [Accepted: 09/02/2015] [Indexed: 12/26/2022] Open
Abstract
Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) genes (miR-SNPs) have attracted increasing attention in recent years due to their involvement in the development of various types of cancer. Therefore, a systematic review on this topic was needed. From 55 scientific publications we collected 20 SNPs, which are located within 18 miRNA encoding genes and have been associated with 16 types of cancer. Among 20 miRNA gene polymorphisms 13 are located within the premature miRNA region, five within mature, and two within mature seed miRNA region. We graphically visualized a network of miRNA-cancer associations which revealed miRNA genes and cancer types with the highest number of connections. Our study showed that, despite a large number of variations currently known to be located within miRNA genes in humans, most of them have not yet been tested for association with cancer. MicroRNA SNPs collected in this study represent only 0.43% of known miRNA gene variations (20/4687). Results of the present study will be useful to researchers investigating the clinical use of miRNAs, such as the roles of miRNAs as diagnostic markers and therapeutic targets.
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Affiliation(s)
- Veronika Pipan
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana,Groblje 3, SI-1230 Domzale, Slovenia.
| | - Minja Zorc
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana,Groblje 3, SI-1230 Domzale, Slovenia.
| | - Tanja Kunej
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana,Groblje 3, SI-1230 Domzale, Slovenia.
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Smolle MA, Pichler M, Haybaeck J, Gerger A. Genetic markers of recurrence in colorectal cancer. Pharmacogenomics 2015; 16:1315-28. [DOI: 10.2217/pgs.15.83] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) worldwide belongs to one of the most frequent cancers affecting both genders. Surgery and 5-fluorouracil-based adjuvant chemotherapy are recommended for patients with high-risk stage II and stage III colon carcinoma. Mutations of genes encoding for specific proteins may have an impact on the time to recurrence. These proteins act over specific signaling pathways, are implicated in metabolic processes and regulate the cell cycle. Though many retrospective studies show strong associations between genetic mutations and the clinical outcome of patients with CRC, currently no validated biomarkers are used in clinical routine settings. Therefore, large prospective validation studies should be carried out in order to strengthen the position of genetic mutations in personalized treatment of patients with CRC.
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Affiliation(s)
- Maria Anna Smolle
- Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Martin Pichler
- Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | | | - Armin Gerger
- Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
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Wang J, Du Y, Liu X, Cho WC, Yang Y. MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer. BIOMED RESEARCH INTERNATIONAL 2015; 2015:823620. [PMID: 26064956 PMCID: PMC4438141 DOI: 10.1155/2015/823620] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 04/06/2015] [Accepted: 04/06/2015] [Indexed: 02/06/2023]
Abstract
MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.
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Affiliation(s)
- Jian Wang
- Human Stem Cell Institute of the General Hospital, Ningxia Medical University, Yinchuan 750004, China
- Department of Colorectal Surgery, The General Hospital of Ningxia Medical University, Yinchuan 750004, China
| | - Yong Du
- Human Stem Cell Institute of the General Hospital, Ningxia Medical University, Yinchuan 750004, China
- Department of Colorectal Surgery, The General Hospital of Ningxia Medical University, Yinchuan 750004, China
| | - Xiaoming Liu
- Human Stem Cell Institute of the General Hospital, Ningxia Medical University, Yinchuan 750004, China
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
| | - Yinxue Yang
- Human Stem Cell Institute of the General Hospital, Ningxia Medical University, Yinchuan 750004, China
- Department of Colorectal Surgery, The General Hospital of Ningxia Medical University, Yinchuan 750004, China
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Su X, Hu Y, Li Y, Cao JL, Wang XQ, Ma X, Xia HF. The polymorphism of rs6505162 in the MIR423 coding region and recurrent pregnancy loss. Reproduction 2015; 150:65-76. [PMID: 25926693 DOI: 10.1530/rep-15-0007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 04/25/2015] [Indexed: 12/30/2022]
Abstract
Although the relationship between polymorphisms in microRNAs (miRNAs) and recurrent pregnancy loss (RPL) has been studied, there is very little data available in the literature. In the present study, we scanned 55 potentially functional polymorphisms in the miRNA coding region in Chinese women with unexplained RPL (URPL; no. 2011-10). The rs6505162 C>A in the MIR423 coding region was found to be significantly associated with the occurrence of human URPL. The rare A allele contributed to an increase in the expression of mature MIR423. C to A substitution in the polymorphism rs6505162 in pre-MIR423 repressed cell proliferation and migratory capacity. Further investigations showed that MIR423 could inversely regulate the expression of proliferation-associated 2 group 4 (PA2G4) by binding the 3'-UTR of PA2G4. Dual-luciferase assay indicated that the A allele in the polymorphism rs6505162 could more effectively suppress the expression of PA2G4 than the C allele could. Collectively, the present data suggest that rs6505162 C>A in pre-MIR423 may contribute to the genetic predisposition to RPL by disrupting the production of mature MIR423 and its target gene, which consequently interferes with MIR423 functioning.
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Affiliation(s)
- Xing Su
- Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
| | - Yi Hu
- Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
| | - Ying Li
- Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
| | - Jing-Li Cao
- Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
| | - Xue-Qin Wang
- Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
| | - Xu Ma
- Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
| | - Hong-Fei Xia
- Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China
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Zhou F, Huang X, Zhang Z, Chen Y, Liu X, Xing J, He X. Functional polymorphisms of ITGB1 are associated with clinical outcome of Chinese patients with resected colorectal cancer. Cancer Chemother Pharmacol 2015; 75:1207-15. [PMID: 25894721 DOI: 10.1007/s00280-015-2745-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 04/02/2015] [Indexed: 01/05/2023]
Abstract
PURPOSE Integrin β1 (ITGB1) has been recognized to play a major role in tumor growth, invasion and metastasis. However, effects of single-nucleotide polymorphisms (SNPs) in ITGB1 gene on the prognosis of patients with colorectal cancer (CRC) have not been reported. METHODS A total of 372 patients with resected colorectal adenocarcinoma were enrolled in our study. Three functional SNPs (rs2230395, rs1187075 and rs1187076) in ITGB1 were selected and genotyped using the Sequenom iPLEX genotyping system. RESULTS We identified two SNPs (rs2230395 and rs1187075) in ITGB1 gene to be significantly associated with CRC overall survival (OS). Compared with the homozygous wild-type (AA) and heterozygous variant (AC), rs2230395 homozygous variant (CC) conferred a 1.55-fold (95 % CI 1.00-2.41, P = 0.049) increased risk of death. Similar result was obtained for homozygous variant (AA) in rs1187075 with a 1.62-fold (95 % CI 1.08-2.42, P = 0.020). In stratified analysis, this association in rs2230395 remained to be significant in patients receiving chemotherapy, but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival in subgroups stratified by rs2230395 and rs1187075 genotypes. We found that chemotherapy resulted in a significantly better OS in patients with the homozygous wild-type (WW) or heterozygous variant (WV) genotype in both rs2230395 and rs1187075 when compared with patients with homozygous variant (VV) genotype. CONCLUSIONS Our data suggest that ITGB1 SNPs might be a prognostic biomarker for CRC patients, especially in those receiving chemotherapy. Our findings warrant validation in larger independent populations.
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Affiliation(s)
- Feng Zhou
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi'an, 710032, China
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Genetic variants of microRNA sequences and susceptibility to sepsis in patients with major blunt trauma. Ann Surg 2015; 261:189-96. [PMID: 24743625 DOI: 10.1097/sla.0000000000000687] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE The objective of this study was to conduct a systematic survey of common precursor microRNA (pre-miRNA) single nucleotide polymorphisms (SNPs) and evaluate their clinical relevance in patients with major blunt trauma. BACKGROUND Recent evidence indicates that small noncoding RNA molecules known as miRNAs can function as important negative gene regulators and are implicated in the pathogenesis of various diseases. METHODS We conducted a 2-stage study to examine the impact of 9 selected SNPs with potential functional significance on the susceptibility to sepsis of 1268 trauma patients (1 screening cohort, n = 666) and 2 independent validated cohorts (n = 286 and n = 316, respectively) in China. RESULTS Among the 9 selected SNPs with potential functional significance, only 1 (miR-608 rs4919510) was found to be strongly associated with a higher risk of developing sepsis and multiple organ dysfunction in all 3 independent study cohorts. An even stronger association was observed for the rs4919510 polymorphism when combining these 3 study cohorts together. In addition, the rs4919510 polymorphism showed a significant correlation with a higher production of proinflammatory cytokines and a lower production of anti-inflammatory cytokines. In vitro experiments further indicated that the G→C variant of this polymorphism could significantly increase the expression of mature miR-608. CONCLUSIONS Our results indicate that the rs4919510G/C SNP in hsa-mir-608 may be a prognostic biomarker for sepsis in patients with major trauma. Further characterization of miRNA SNPs may open new avenues for studying sepsis and developing novel therapeutic approaches.
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Muhammad S, Kaur K, Huang R, Zhang Q, Kaur P, Yazdani HO, Bilal MU, Zheng J, Zheng L, Wang XS. MicroRNAs in colorectal cancer: Role in metastasis and clinical perspectives. World J Gastroenterol 2014; 20:17011-17019. [PMID: 25493013 PMCID: PMC4258569 DOI: 10.3748/wjg.v20.i45.17011] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 06/19/2014] [Accepted: 07/30/2014] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients’ outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.
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Xie WQ, Tan SY, Wang XF. Effect of a common genetic variant microRNA-146a rs2910164 on colorectal cancer: a meta-analysis. J Dig Dis 2014; 15:647-53. [PMID: 25283877 DOI: 10.1111/1751-2980.12201] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE There is emerging evidence that the microRNA-146a (miR-146a) rs2910164 polymorphism might be associated with the susceptibility to colorectal cancer (CRC). However, previous published studies have failed to achieve a definitive conclusion. We aimed to address this issue in an updated meta-analysis. METHODS A comprehensive literature search was conducted in PubMed, Embase, China BioMedicine, the Cochrane Library and Google Scholar to identify eligible studies. Case-control studies written in English that evaluated the association between miR-146a polymorphism and CRC were included. Odds ratio and 95% confidence interval were calculated in the quantitative synthesis. RESULTS Overall seven case-control studies including a total of 2978 cases and 3576 cancer-free or healthy controls were enrolled in the meta-analysis. The results indicated that there was no association between miR-146a G/C rs2910164 polymorphism and CRC risk either in the overall analysis or among Asians, when stratified on the basis of ethnicity. CONCLUSION miR-146a G/C genetic polymorphism was not related to the susceptibility to CRC.
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Affiliation(s)
- Wen Qun Xie
- Key Laboratory of Digestive Disease, Department of Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, China
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Pardini B, Rosa F, Naccarati A, Vymetalkova V, Ye Y, Wu X, di Gaetano C, Buchler T, Novotny J, Matullo G, Vodicka P. Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients. Carcinogenesis 2014; 36:82-6. [PMID: 25368035 DOI: 10.1093/carcin/bgu224] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. It is routinely cured by a 5-fluorouracil (5-FU)-based chemotherapy which improves outcomes in patients. We investigated the effect of single nucleotide polymorphisms (SNPs) in two microRNA (miRNA)-encoding genes that have been previously reported as important in prognosis in patients with stage III CRC and treated with 5-FU-based chemotherapy. Two SNPs (rs4919510 in miR-608 and rs213210 in miR-219-1) were genotyped in 1083 CRC patients recruited in the Czech Republic to evaluate their effect on clinical outcomes. Carriers of the variant T allele in rs213210 and receiving 5-FU chemotherapy were associated with a significantly worse survival [hazard ratio (HR) = 2.18; 95% confidence interval (CI): 1.20-3.98; adjusted P = 0.01] and an increased risk of relapse (HR = 1.94; 95% CI: 1.16-3.25; adjusted P = 0.01). After further stratification for tumor grading, stage III patients carrying the G allele of rs4919510 and undergoing adjuvant chemotherapy were at decreased risk of relapse (HR = 0.44; 95% CI: 0.20-0.94; adjusted P = 0.03). The present study confirms that variations in miRNA-encoding genes may be an important factor for modulating CRC prognosis and predicting therapy response.
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Affiliation(s)
- Barbara Pardini
- Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy,
| | - Fabio Rosa
- Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Alessio Naccarati
- Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Molecular Biology of Cancer, Institute of Experimental Medicine, 14200 Prague, Czech Republic
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine, 14200 Prague, Czech Republic, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic
| | - Yuanqing Ye
- Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, 77030 Houston, TX, USA
| | - Xifeng Wu
- Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, 77030 Houston, TX, USA
| | - Cornelia di Gaetano
- Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Tomas Buchler
- Department of Surgery, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic, Department of Oncology, Thomayer University Hospital, Prague, Czech Republic and
| | - Jan Novotny
- Department of Oncology, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic
| | - Giuseppe Matullo
- Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine, 14200 Prague, Czech Republic, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic
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Xia L, Ren Y, Fang X, Yin Z, Li X, Wu W, Guan P, Zhou B. Prognostic role of common microRNA polymorphisms in cancers: evidence from a meta-analysis. PLoS One 2014; 9:e106799. [PMID: 25337946 PMCID: PMC4206268 DOI: 10.1371/journal.pone.0106799] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Accepted: 08/01/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The morbidity and mortality of cancer increase remarkably every year. It's a heavy burden for family and society. The detection of prognostic biomarkers can help to improve the theraputic effect and prolong the lifetime of patients. microRNAs have an influential role in cancer prognosis. The results of articles discussing the relationship between microRNA polymorphisms and cancer prognosis are inconsistent. METHODS We conduct a meta-analysis of 19 publications concerning the association of four common polymorphisms, mir-146a rs2910164, mir-149 rs2292832, mir-196a2 rs11614913 and mir-499 rs3746444, with cancer prognosis. Pooled Hazard Ratios with 95% Confidence Intervals for the relationship between four genetic polymorphisms and Overall Survival, Recurrence-free Survival, Disease-free survival, recurrence are calculated. Subgroup analysis by population and type of tumor are conducted. RESULTS GG genotype of mir-146a may be the protective factor for overall survival, especially in Caucasian population. C-containing genotypes of mir-196a2 act as a risk role for overall survival. The same result exists in Asian population, in Non-Small Cell Lung Cancer and digestive cancer. The patients with C allele of mir-149 have a better overall survival, especially in Non-Small Cell Lung Cancer. No significant results are obtained for mir-499 polymorphisms. CONCLUSIONS Genetic polymorphisms in mir-146a, mir-196a2 and mir-149 may be associated with overall survival. This effect varies with different types of cancer. Genetic polymorphism in mir-499 may have nothing to do with cancer prognosis.
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Affiliation(s)
- Lingzi Xia
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
| | - Yangwu Ren
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
| | - Xue Fang
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
| | - Zhihua Yin
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
| | - Xuelian Li
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
| | - Wei Wu
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
| | - Peng Guan
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
| | - Baosen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning Province, China
- Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China
- * E-mail:
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Dong Y, Yu J, Ng SS. MicroRNA dysregulation as a prognostic biomarker in colorectal cancer. Cancer Manag Res 2014; 6:405-22. [PMID: 25342918 PMCID: PMC4206254 DOI: 10.2147/cmar.s35164] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most potentially curable cancers, yet it remains the fourth most common overall cause of cancer death worldwide. The identification of robust molecular prognostic biomarkers can refine the conventional tumor–node–metastasis staging system, avoid understaging of tumor, and help pinpoint patients with early-stage CRC who may benefit from aggressive treatments. Recently, epigenetic studies have provided new molecular evidence to better categorize the CRC subtypes and predict clinical outcomes. In this review, we summarize recent findings concerning the prognostic potential of microRNAs (miRNAs) in CRC. We first discuss the prognostic value of three tissue miRNAs (miR-21-5p, miR-29-3p, miR-148-3p) that have been examined in multiple studies. We also summarize the dysregulation of miRNA processing machinery DICER in CRC and its association with risk for mortality. We also reviewe the potential application of miRNA-associated single-nucleotide polymorphisms as prognostic biomarkers for CRC, especially the miRNA-associated polymorphism in the KRAS gene. Last but not least, we discuss the microsatellite instability-related miRNA candidates. Among all these candidates, miR-21-5p is the most promising prognostic marker, yet further prospective validation studies are required before it can go into clinical usage.
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Affiliation(s)
- Yujuan Dong
- Division of Colorectal Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong ; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Jun Yu
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Simon Sm Ng
- Division of Colorectal Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong ; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
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Zhang MF, Zheng MC, Liu WY, Wen YS, Wu XD, Liu QW. The influence of demographics, psychological factors and self-efficacy on symptom distress in colorectal cancer patients undergoing post-surgical adjuvant chemotherapy. Eur J Oncol Nurs 2014; 19:89-96. [PMID: 25227458 DOI: 10.1016/j.ejon.2014.08.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 07/31/2014] [Accepted: 08/12/2014] [Indexed: 01/02/2023]
Abstract
PURPOSE To explore the influence of self-efficacy and demographic, disease-related, and psychological factors on symptom distress among Chinese colorectal cancer patients receiving postoperative adjuvant chemotherapy. METHODS Two-hundred and fifty-two colorectal cancer patients who had undergone postoperative adjuvant chemotherapy completed Chinese versions of M. D. Anderson Symptom Inventory (MDASI-GI), Stanford Inventory of Cancer Patient Adjustment (SICPA), and Hospital Anxiety and Depression Scale (HADS). Associations between patients' self-efficacy and demographic, disease-related, psychological factors and symptom distress were examined. RESULTS Patients' overall symptom distress level was mild; MDASI median subscale scores showed mild symptom severity and symptom interference. Anxiety and depression were positively associated with symptom distress. Multivariable analysis showed that more severe symptoms were associated with age ≥60 years, female gender, suburban residence, body mass index <18.5, and stage III cancer. Age ≥60 years, female gender, marital status of single or divorced, and suburban residence were associated with greater symptom interference with daily activities. Greater self-efficacy was associated with milder symptoms severity and less symptom interference with daily life. After adjusting for confounders, patients with higher SICPA scores had less symptom distress. CONCLUSIONS Self-efficacy is strongly associated with reduced symptom severity and symptom interference with daily life in CRC patients. Symptom severity is associated with age >60 years, female gender, body mass index <18.5, suburban residence and stage III disease. Nurse-administered self-efficacy interventions may help to improve self-efficacy and reduce symptom distress.
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Affiliation(s)
- Mei-fen Zhang
- School of Nursing, Sun Yat-sen University, Guangzhou 510080, China.
| | - Mei-chun Zheng
- Department of Nursing, Cancer Center of Sun Yat-sen University, Guangzhou 510275, China
| | - Wei-yan Liu
- Department of Nursing, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China
| | - Yong-shan Wen
- Department of Nursing, Cancer Center of Sun Yat-sen University, Guangzhou 510275, China
| | - Xiao-dan Wu
- Department of Nursing, Cancer Center of Sun Yat-sen University, Guangzhou 510275, China
| | - Qian-wen Liu
- Department of Nursing, Cancer Center of Sun Yat-sen University, Guangzhou 510275, China
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Zhang W, Yi X, Guo S, Shi Q, Wei C, Li X, Gao L, Wang G, Gao T, Wang L, Li C. A single-nucleotide polymorphism of miR-146a and psoriasis: an association and functional study. J Cell Mol Med 2014; 18:2225-34. [PMID: 25209759 PMCID: PMC4224556 DOI: 10.1111/jcmm.12359] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Accepted: 06/10/2014] [Indexed: 01/21/2023] Open
Abstract
Epidermal growth factor receptor (EGFR), which is overexpressed in psoriatic lesions, has been proven to contribute to the hyperproliferation of keratinocytes in psoriasis. Single nucleotide polymorphisms (SNPs) involved in miRNAs that can regulate the expression of EGFR could potentially influence the development of psoriasis. The present study investigated the association between a functional SNP of rs2910164 in miR-146a and the risk of psoriasis in the Chinese Han population. A total of 521 Han Chinese patients with psoriasis and 582 healthy controls were recruited in this study. The miR-146a rs2910164 SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Overall, a significantly increased risk of psoriasis was associated with the rs2910164 miR-146a CG and GG genotypes (adjusted OR, 1.38; 95% CI, 1.06–1.80). Furthermore, the rs2910164G allele in miR-146a attenuated its inhibitory regulation on the expression of EGFR as well as the proliferation of human keratinocytes, and lowered the level of miR-146a in the psoriatic lesions. These findings indicate that the rs2910164G allele in miR-146a weakens its suppression on the proliferation of keratinocytes probably through the decreased inhibition of the target gene, EGFR, which may account for the increased risk of psoriasis in this study population.
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Affiliation(s)
- Weigang Zhang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
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Wang R, Zhang J, Ma Y, Chen L, Guo S, Zhang X, Ma Y, Wu L, Pei X, Liu S, Wang J, Hu H, Liu J. Association study of miR‑149 rs2292832 and miR‑608 rs4919510 and the risk of hepatocellular carcinoma in a large‑scale population. Mol Med Rep 2014; 10:2736-44. [PMID: 25190221 DOI: 10.3892/mmr.2014.2536] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Accepted: 06/05/2014] [Indexed: 11/06/2022] Open
Abstract
Polymorphisms in pre‑microRNAs (miRNAs) or mature miRNAs may influence miRNA processing or target binding, thus contributing to tumorigenesis and cancer development. The present study aimed to evaluate whether miR‑149 rs2292832 (C>T) and miR‑608 rs4919510 (G>C) are associated with the risk and clinical characteristics of hepatocellular carcinoma (HCC) in a large‑scale population. miR‑149 rs2292832 and miR‑608 rs4919510 were genotyped in a total of 993 patients with HCC and 992 unrelated healthy subjects by Sequenom MassARRAY. The results showed that, compared with the reference CC genotype, the TC+TT genotype of miR‑149 was more highly associated with HCC [CC vs. TC+TT: Odds ratio (OR)=1.384, 95% confidence interval (CI)=1.013‑1.892, P=0.041], and was also associated with an increased risk of hepatitis B virus (HBV)‑associated HCC (CC vs. TC+TT: OR=1.453, 95% CI=1.034‑2.042, P=0.031). However, no significant association between miRNA‑608 rs4919510 and the risk of HCC/HBV‑associated HCC was found. In addition, these two SNPs were shown not to be correlated with a range of clinical characteristics. The present study may provide an indicator for identification of the high risk of HCC in patients.
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Affiliation(s)
- Rui Wang
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Jun Zhang
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Yanyun Ma
- Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China
| | - Linqi Chen
- Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China
| | - Shicheng Guo
- Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China
| | - Xiaojiao Zhang
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Yunfang Ma
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Lijun Wu
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Xiaoyu Pei
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Siran Liu
- Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA
| | - Jiucun Wang
- Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China
| | - Heping Hu
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, P.R. China
| | - Jie Liu
- Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
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