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Morales-González S, Calaf GM, Acuña M, Tapia JC, Jara L. The miR-146a Single Nucleotide Polymorphism rs2910164 Promotes Proliferation, Chemoresistance, Migration, Invasion, and Apoptosis Suppression in Breast Cancer Cells. Cells 2025; 14:612. [PMID: 40277937 PMCID: PMC12025401 DOI: 10.3390/cells14080612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/27/2025] [Accepted: 04/16/2025] [Indexed: 04/26/2025] Open
Abstract
Breast cancer (BC) is the most common malignant disease in women worldwide. Several studies have reported that microRNA-146a (miR-146a) dysregulation plays a role in multiple cancers, including BC. However, the mechanism underlying this association is controversial, possibly reflecting diverse roles for this miR in different types of cancer. The SNP rs2910164:G>C, located within the miR-146a precursor, has been linked to a BC risk. Our group previously showed a specific association between rs2910164:G>C and an increased BC risk in patients with early-onset sporadic BC. There are no studies in the literature that evaluate the functional consequences of the rs2910164 polymorphism in the BC process. Therefore, the goal of the present study was to evaluate in vitro the effect of the SNP rs2910164:G>C on BC progression in luminal A and triple-negative cell lines. We found that rs2910164:G>C upregulated the expression of two mature miR-146a sequences, 3p and 5p. Furthermore, pre-miR-146a-C enhanced proliferation, migration, and invasion in luminal A and triple-negative breast cells, as well as decreasing cisplatin-induced apoptosis. Interestingly, the pre-miR-146a C allele decreased cisplatin resistance in MCF-7 cells but increased cisplatin resistance in MDA-MB-231 cells. We propose that the rs2910164 C allele promotes miR-146a overexpression, which is causally involved in proliferation, migration, invasion, apoptosis, and cisplatin resistance.
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Affiliation(s)
- Sarai Morales-González
- Núcleo Interdisciplinario de Biología y Genética, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia, Santiago 8380000, Chile; (S.M.-G.); (M.A.)
| | - Gloria M. Calaf
- Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1010069, Chile;
| | - Mónica Acuña
- Núcleo Interdisciplinario de Biología y Genética, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia, Santiago 8380000, Chile; (S.M.-G.); (M.A.)
| | - Julio C. Tapia
- Núcleo Interdisciplinario de Biología y Genética, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia, Santiago 8380000, Chile; (S.M.-G.); (M.A.)
| | - Lilian Jara
- Núcleo Interdisciplinario de Biología y Genética, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia, Santiago 8380000, Chile; (S.M.-G.); (M.A.)
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Tutunchi S, Nourmohammadi P, Tofigh R, Akhavan S, Zare M, Samavarchi Tehrani S, Panahi G. The critical role and functional mechanism of microRNA-146a in doxorubicin-induced apoptosis in breast cancer cells. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2024; 44:124-135. [PMID: 38531028 DOI: 10.1080/15257770.2024.2330592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 03/28/2024]
Abstract
BACKGROUND Breast cancer among women is the most frequently diagnosed cancer and the leading cause of death worldwide. There many advances in diagnosing and treating this disease, early diagnosis and treatment are still a significant challenge in the early stages. In recent years, microRNAs have attracted much attention in cancer diagnosis and treatment. However, the role of miR-146a in breast cancer is still controversial. We aimed to investigate the roles of miR-146a in apoptosis in breast cancer cells. METHODS A microarray dataset from the GEO database was selected, and using the GEO2R tool, the gene expression profile of this dataset was extracted. Then, the target scan database was used to explore the miR-146a target genes. The link between the signaling pathways was collected. We used miR-146a mimic, which was transfected to the MCF-7 cells to investigate the miR-146a roles in the apoptosis. The expression levels of miR-146a and BAX, BCL-2, and p-21(most essential genes in the apoptosis) were quantified by qPCR and western blot analysis. RESULTS Our findings indicated that doxorubicin induces miR-146a expression. In addition, overexpression of miR-146a affected MCF-7 cell viability, induced apoptosis, and led to reduced expression levels of BCL-2 and P-21, as well as increased BAX expression levels. CONCLUSION Considering the role of doxorubicin in inducing apoptosis and increasing the expression of miR-146a, it can be suggested that this miR is involved in inducing apoptosis in BC cells. In addition, miR-146a can be considered a therapeutic candidate.
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Affiliation(s)
- Sara Tutunchi
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Parisa Nourmohammadi
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Roghayeh Tofigh
- Department of Animal Biology, Tabriz University, Tabriz, Iran
| | - Saeedeh Akhavan
- Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University (IAU), Tehran, Iran
| | - Mina Zare
- Recombinant Protein Laboratory, Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sadra Samavarchi Tehrani
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Science, Tehran, Iran
| | - Ghodratollah Panahi
- Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Can Demirdöğen B, Öztürk Başer T, Köylü MT, Özge G, Gürbüz Köz Ö, Mumcuoğlu T. Circulating miRNAs and their functional genetic variants in pseudoexfoliative glaucoma: potential of miR-146a-5p as a diagnostic biomarker. Int Ophthalmol 2023; 43:3953-3967. [PMID: 37420124 DOI: 10.1007/s10792-023-02797-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 06/22/2023] [Indexed: 07/09/2023]
Abstract
PURPOSE The etiology and pathogenesis of pseudoexfoliation syndrome (PEX) and its advancement into pseudoexfoliative glaucoma (PEG) are not fully understood. In this study, we aimed to evaluate the possible role played by two circulating microRNAs (miR-146a-5p and miR-196a-5p) in plasma and their functional genetic variants MIR146A rs2910164 and MIR196A2 rs11614913 in susceptibility to PEG or PEX. METHODS Plasma miRNA relative expression of 27 patients with PEG, 25 patients with PEX and 27 controls was determined using quantitative RT-PCR, and fold change was calculated using the 2-ΔΔCt method. Genotyping of 300 patients with PEG, 300 patients with PEX, and 300 controls was performed using a PCR-restriction fragment length polymorphism analysis. RESULT Plasma miR-146a-5p relative expression was significantly elevated in patients with PEG (3.9-fold) (P < .000) and patients with PEX (2.7-fold) relative to controls (P = .001). The diagnostic ability of plasma miR-146a-5p expression fold change was good for discriminating PEG vs. controls (AUC = 0.897, P < .000), and the optimal decision threshold was 1.83 (sensitivity = 74%, specificity = 93%). Plasma miR-196a-5p relative expression did not differ significantly between study groups. No significant difference in terms of the minor allele frequency or the distribution of genotypes for MIR146A rs2910164 G/C or MIR196A2 rs11614913 C/T was observed between study groups. CONCLUSIONS Circulating miR-146a-5p can contribute to the risk of PEX/PEG. Therefore, we propose that plasma miR-146a-5p can be developed as a potential biomarker for the minimally invasive diagnoses of PEX/PEG and as a potential therapeutic target with further studies.
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Affiliation(s)
- Birsen Can Demirdöğen
- Department of Biomedical Engineering, TOBB University of Economics and Technology, 06560, Söğütözü, Ankara, Turkey.
| | - Tuğba Öztürk Başer
- Department of Biomedical Engineering, TOBB University of Economics and Technology, 06560, Söğütözü, Ankara, Turkey
| | - Mehmet Talay Köylü
- Department of Ophthalmology, Gülhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Gökhan Özge
- Department of Ophthalmology, Gülhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Özlem Gürbüz Köz
- Department of Ophthalmology, Ankara City Hospital, Ankara, Turkey
| | - Tarkan Mumcuoğlu
- Department of Ophthalmology, Ankara Güven Hospital, Ankara, Turkey
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Zhou H, Hao X, Zhang P, He S. Noncoding RNA mutations in cancer. WILEY INTERDISCIPLINARY REVIEWS. RNA 2023; 14:e1812. [PMID: 37544928 DOI: 10.1002/wrna.1812] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 07/14/2023] [Accepted: 07/17/2023] [Indexed: 08/08/2023]
Abstract
Cancer is driven by both germline and somatic genetic changes. Efforts have been devoted to characterizing essential genetic variations in cancer initiation and development. Most attention has been given to mutations in protein-coding genes and associated regulatory elements such as promoters and enhancers. The development of sequencing technologies and in silico and experimental methods has allowed further exploration of cancer predisposition variants and important somatic mutations in noncoding RNAs, mainly for long noncoding RNAs and microRNAs. Association studies including GWAS have revealed hereditary variations including SNPs and indels in lncRNA or miRNA genes and regulatory regions. These mutations altered RNA secondary structures, expression levels, and target recognition and then conferred cancer predisposition to carriers. Whole-exome/genome sequencing comparing cancer and normal tissues has revealed important somatic mutations in noncoding RNA genes. Mutation hotspots and somatic copy number alterations have been identified in various tumor-associated noncoding RNAs. Increasing focus and effort have been devoted to studying the noncoding region of the genome. The complex genetic network of cancer initiation is being unveiled. This article is categorized under: RNA in Disease and Development > RNA in Disease.
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Affiliation(s)
- Honghong Zhou
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Xinpei Hao
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Peng Zhang
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Shunmin He
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
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Liu H, Sun L, Liu X, Wang R, Luo Q. Associations between non-coding RNAs genetic polymorphisms with ovarian cancer risk: A systematic review and meta-analysis update with trial sequential analysis. Medicine (Baltimore) 2023; 102:e35257. [PMID: 37773807 PMCID: PMC10545158 DOI: 10.1097/md.0000000000035257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 08/25/2023] [Indexed: 10/01/2023] Open
Abstract
BACKGROUND This systemic review and meta-analysis seeks to systematically analyze and summarize the association between non-coding RNA polymorphisms and ovarian cancer risk. METHODS We searched PubMed, Web of Science and CNKI for available articles on non-coding RNA polymorphisms in patients with ovarian cancer from inception to March 1, 2023. The quality of each study included in the meta-analysis was rated according to the Newcastle-Ottawa Scale.Odds ratios (ORs) with their 95% confidence intervals (95% CI) were used to assess associations. Chi-square Q-test combined with inconsistency index (I2) was used to test for heterogeneity among studies. Lastly, trial sequential analysis (TSA) software was used to verify the reliability of meta-analysis results, and in-silico miRNA expression were also performed. The meta-analysis was registered with PROSPERO (No. CRD42023422091). RESULTS A total of 17 case-control studies with 18 SNPs were selected, including 2 studies with H19 rs2107425 and HOTAIR rs4759314, and 5 studies with miR-146a rs2910164 and miR-196a rs11614913. Significant associations were found between H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 and ovarian cancer risk. Three genetic models of H19 rs2107425 (CT vs TT (heterozygote model): OR = 1.36, 95% CI = 1.22-1.52, P < .00001; CC + CT vs TT (dominant model): OR = 1.12, 95% CI = 1.02-1.24, P = .02; and CC vs CT + TT (recessive model): OR = 1.23, 95% CI = 1.16-1.31, P < .00001), 2 genetic models of miR-146a rs2910164 (allele model: OR = 1.75, 95% CI = 1.05-2.91, P = .03; and heterozygote model: OR = 0.33, 95% CI = 0.11-0.98, P = .05), 3 genetic models of miR-196a rs11614913 (allele model: OR = 0.70, 95% CI = 0.59-0.82, P < .0001; dominant model: OR = 1.62, 95% CI = 1.18-2.24, P = .0001; and recessive model: OR = 0.70, 95% CI = 0.57-0.87, P = .03) were statistically linked to ovarian cancer risk. Subgroup analysis for miR-146a rs2910164 was performed according to ethnicity. No association was found in any genetic model. The outcomes of TSA also validated the findings of this meta-analysis. CONCLUSION This study summarizes that H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 polymorphisms are significantly linked with the risk of ovarian cancer, and moreover, large-scale and well-designed studies are needed to validate our result.
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Affiliation(s)
- Huaying Liu
- Department of Traditional Chinese Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Lili Sun
- Department of Gynaecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiaoping Liu
- Department of Geriatrics, The Central Hospital of Xianning, Xianning, China
| | - Ruichai Wang
- Department of Geriatrics, The Central Hospital of Xianning, Xianning, China
| | - Qinqin Luo
- Department of Traditional Chinese Medicine, Wuhan No.1 Hospital, Wuhan, China
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Tiwari S, Pandey R, Kumar V, Das S, Gupta V, Vishwakarma S, Nema R, Sindhuja T, Hashmi S, Kumar A. Association of single nucleotide polymorphism miRNA-146a (rs2910164) with increased predisposition to oral squamous cell carcinoma in central India population. Cancer Biomark 2023; 38:203-214. [PMID: 37545224 DOI: 10.3233/cbm-230064] [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] [Indexed: 08/08/2023]
Abstract
BACKGROUND miRNAs play a crucial role in the genesis of cancer, either as tumor suppressor genes or as oncogenes. Single Nucleotide Polymorphisms (SNPs) in the seed region of microRNAs (miRNAs) can dysregulate their levels in the tissues and thereby affect carcinogenesis. The association of SNP in miR-146a (rs2910164) with the risk of oral squamous cell carcinoma (OSCC) has not been understood. OBJECTIVE In the present study, we have determined the association and functional significance of miR-146a (rs2910164) SNP with susceptibility to OSCC predisposition. METHODS In the present case-control study, we enrolled 430 subjects from central India (215 OSCC cases and 215 healthy controls). We performed genotyping by Kompetitive Allele Specific PCR (KASP), and their correlation with OSCC susceptibility was analyzed. miRNA expression profiling in tumor tissues and adjacent normal tissues from six OSCC patients was done by a NanoString n-Counter-based assay. Subsequently, gene ontology and pathway analysis were performed with FunRich version 3.13. RESULTS The CC genotype of rs2910164 miR-146a was significantly associated with the increased risk for OSCC (CC vs GC, OR = 2.62; 95% CI: 1.48-4.66; p value = 0.001). However, the GC genotype was protective with GC vs CC (OR = 0.38, 95%CI =0.21-0.67, p-value = 0.001), and GC vs GG (OR = 0.58, 95%CI = 0.37-0.89, p-value = 0.01). CONCLUSION Our finding suggests that SNP rs2910164 of miR-146a may be a genetic risk factor for OSCC susceptibility in the Central India population. However, more extensive multicenter studies are required to validate these findings.
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Affiliation(s)
- Shikha Tiwari
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Ritu Pandey
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Vinay Kumar
- Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Saikat Das
- Department of Radiotherapy, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Vikas Gupta
- Department of ENT and Head and Neck Surgery, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Supriya Vishwakarma
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Rajeev Nema
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Tulasi Sindhuja
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Sana Hashmi
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
| | - Ashok Kumar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Saket Nagar, Bhopal, India
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Dos Santos JS, Bonafé GA, Lourenço GJ, Ortega MM. Evaluating Single-Nucleotide Variants in MicroRNA Targeting Sites and Mature MicroRNA In Vitro Cell Culture by Luciferase Reporter Gene Assays. Methods Mol Biol 2023; 2595:185-201. [PMID: 36441463 DOI: 10.1007/978-1-0716-2823-2_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
MicroRNAs (miRs) are small non-coding RNAs of 21-24 nucleotides in length that modulate gene expression by targeting the untranslated region (UTR) of mRNA. Single-nucleotide variants (SNVs) in primary miRs (pri-miRs), precursor miRs (pre-miRs), promoters of pri-miRs, and seed regions can affect miR stability or processing, may influence mature miR expression, and can affect target gene identification, respectively. The present protocol tests the binding and activity of miRs on 3'-UTR target sequences based on the expression of luciferase as a reporter gene fused to the UTR sequence in the presence of plasmids containing pre-miR of interest to test in vitro cell culture assay.
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Affiliation(s)
- Jéssica Silva Dos Santos
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University, Bragança Paulista, São Paulo, Brazil
| | - Gabriel Alves Bonafé
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University, Bragança Paulista, São Paulo, Brazil
| | - Gustavo Jacob Lourenço
- Laboratory of Cancer Genetics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
| | - Manoela Marques Ortega
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University, Bragança Paulista, São Paulo, Brazil.
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Consequences of genetic variants in miRNA genes. Comput Struct Biotechnol J 2022; 20:6443-6457. [DOI: 10.1016/j.csbj.2022.11.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/16/2022] [Accepted: 11/16/2022] [Indexed: 11/20/2022] Open
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da Silva MNS, da Veiga Borges Leal DF, Sena C, Pinto P, Gobbo AR, da Silva MB, Salgado CG, dos Santos NPC, dos Santos SEB. Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population. Int J Mol Sci 2022; 23:ijms231810628. [PMID: 36142557 PMCID: PMC9503809 DOI: 10.3390/ijms231810628] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/01/2022] [Accepted: 09/06/2022] [Indexed: 11/16/2022] Open
Abstract
Leprosy is a chronic neurodermatological disease caused by the bacillus Mycobacterium leprae. Recent studies show that SNPs in genes related to miRNAs have been associated with several diseases in different populations. This study aimed to evaluate the association of twenty-five SNPs in genes encoding miRNAs related to biological processes and immune response with susceptibility to leprosy and its polar forms paucibacillary and multibacillary in the Brazilian Amazon. A total of 114 leprosy patients and 71 household contacts were included in this study. Genotyping was performed using TaqMan Open Array Genotyping. Ancestry-informative markers were used to estimate individual proportions of case and control groups. The SNP rs2505901 (pre-miR938) was associated with protection against the development of paucibacillary leprosy, while the SNPs rs639174 (DROSHA), rs636832 (AGO1), and rs4143815 (miR570) were associated with protection against the development of multibacillary leprosy. In contrast, the SNPs rs10739971 (pri-let-7a1), rs12904 (miR200C), and rs2168518 (miR4513) are associated with the development of the paucibacillary leprosy. The rs10739971 (pri-let-7a1) polymorphism was associated with the development of leprosy, while rs2910164 (miR146A) and rs10035440 (DROSHA) was significantly associated with an increased risk of developing multibacillary leprosy.
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Affiliation(s)
- Mayara Natália Santana da Silva
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
- Laboratório de Biologia e Eletrofisiologia Celular, Seção de Parasitologia, Instituto Evandro Chagas, Ananindeua 67030-000, PA, Brazil
- Correspondence:
| | - Diana Feio da Veiga Borges Leal
- Núcleo de Pesquisas em Oncologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66073-000, PA, Brazil
| | - Camille Sena
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
| | - Pablo Pinto
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
- Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
| | - Angélica Rita Gobbo
- Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
| | - Moises Batista da Silva
- Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
| | - Claudio Guedes Salgado
- Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
| | - Ney Pereira Carneiro dos Santos
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
- Núcleo de Pesquisas em Oncologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66073-000, PA, Brazil
| | - Sidney Emanuel Batista dos Santos
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil
- Núcleo de Pesquisas em Oncologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66073-000, PA, Brazil
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Khajah MA, Al-Ateyah A, Luqmani YA. MicroRNA expression profiling of endocrine sensitive and resistant breast cancer cell lines. Biochem Biophys Rep 2022; 31:101316. [PMID: 35879960 PMCID: PMC9307586 DOI: 10.1016/j.bbrep.2022.101316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 11/27/2022] Open
Abstract
Background Methods Results Conclusions
Around 50–60% of microRNAs were significantly differentially expressed between ER- and ER + breast cancer cell lines. Transfection of miR-200c-3p mimic into ER -ve cells induced MET and reduced cell motility. Transfecting of miR-449a inhibitor into ER -ve cells reduced cell invasion but did not induce EMT.
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Ni L, Tang C, Wang Y, Wan J, Charles MG, Zhang Z, Li C, Zeng R, Jin Y, Song P, Wei M, Li B, Zhang J, Wu Z. Construction of a miRNA-Based Nomogram Model to Predict the Prognosis of Endometrial Cancer. J Pers Med 2022; 12:jpm12071154. [PMID: 35887651 PMCID: PMC9318842 DOI: 10.3390/jpm12071154] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 12/11/2022] Open
Abstract
Objective: To investigate the differential expression of microRNA (miRNA) in patients with endometrial cancer and its relationship with prognosis and survival. Method: We used The Cancer Genome Atlas (TCGA) database to analyze differentially expressed miRNAs in endometrial cancer tissues and adjacent normal tissues. In addition, we successfully screened out key microRNAs to build nomogram models for predicting prognosis and we performed survival analysis on the key miRNAs as well. Result: We identified 187 differentially expressed miRNAs, which includes 134 up-regulated miRNAs and 53 down-regulated miRNAs. Further univariate Cox regression analysis screened out 47 significantly differentially expressed miRNAs and selected 12 miRNAs from which the prognostic nomogram model for ECA patients by LASSO analysis was constructed. Survival analysis showed that high expression of hsa-mir-138-2, hsa-mir-548f-1, hsa-mir-934, hsa-mir-940, and hsa-mir-4758 as well as low-expression of hsa-mir-146a, hsa-mir-3170, hsa-mir-3614, hsa-mir-3616, and hsa-mir-4687 are associated with poor prognosis in EC patients. However, significant correlations between the expressions levels of has-mir-876 and hsa-mir-1269a and patients' prognosis are not found. Conclusion: Our study found that 12 significantly differentially expressed miRNAs might promote the proliferation, invasion, and metastasis of cancer cells by regulating the expression of upstream target genes, thereby affecting the prognosis of patients with endometrial cancer.
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Affiliation(s)
- Leyi Ni
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Chengyun Tang
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Yuning Wang
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Jiaming Wan
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Morgan G. Charles
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Zilong Zhang
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Chen Li
- Department of Biology, Chemistry, Pharmacy, Free University of Berlin, 14195 Berlin, Germany;
| | - Ruijie Zeng
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Yiyao Jin
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Penghao Song
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Ming Wei
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Bocen Li
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
| | - Jin Zhang
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Correspondence: (J.Z.); (Z.W.)
| | - Zhenghao Wu
- School of Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health, Russian Federation, 8/2 Trubetskaya Street, 119991 Moscow, Russia; (L.N.); (C.T.); (Y.W.); (J.W.); (M.G.C.); (Z.Z.); (R.Z.); (Y.J.); (P.S.); (M.W.); (B.L.)
- Correspondence: (J.Z.); (Z.W.)
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Ezat SA, Haji AI. Study of association between different microRNA variants and the risk of idiopathic recurrent pregnancy loss. Arch Gynecol Obstet 2022; 306:1281-1286. [PMID: 35841423 DOI: 10.1007/s00404-022-06663-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 06/07/2022] [Indexed: 11/24/2022]
Abstract
AIM Recurrent pregnancy loss (RPL) is a common reproductive disorder among women and a major cause of infertility among them; however, the underlying causes of RPL remain unknown which have led to great difficulties and complications in the treatment. MicroRNAs (miRNA) have been shown to be a potential diagnosis tools in different reproductive disorders. This study aimed to investigate the association of four different miRNA variants with the risk of idiopathic RPL (iRPL). METHODS A total of 450 women including 225 patients and 225 controls were recruited in this study. DNA was extracted, and genotyped by PCR method. Haplotype analysis, as well as linkage disequilibrium between SNPs, was performed. CONCLUSION This study suggested that rs4636297, rs41291957, and rs353292, but not rs531564 can play a risk factor role for iRLP.
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Affiliation(s)
- Shayma Abd Ezat
- Department of Obstetrics and Gynecology, College of Medicine, Iraqi Board in Obstetrics/Gynecology, Hawler Medical University, Erbil, Kurdistan Region, 54612504, Iraq.
| | - Azheen Ismael Haji
- Department of Obstetrics and Gynecology, Maternity Teaching Hospital, Erbil, Kurdistan Region, Iraq
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Tian J, Dong Y, Chang S, Wang Y, Shen C, Che G. Epidemiological evidence for associations between variants in microRNA and cancer risk. Carcinogenesis 2022; 43:321-337. [PMID: 35084494 DOI: 10.1093/carcin/bgac011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 01/16/2022] [Accepted: 01/25/2022] [Indexed: 02/05/2023] Open
Abstract
Numerous papers have reported variants in microRNAs (miRNAs) associated with cancer risk; these results, however, are controversial. We seek to offer an updated, comprehensive synopsis of genetic associations between single nucleotide polymorphisms (SNPs) in miRNAs and cancer risk. We did a systematic field synopsis and meta-analysis to investigate 29 SNPs in 24 miRNAs associated with risk of 18 different kinds of cancer based on data from 247 eligible articles. We graded levels of cumulative epidemiological evidence of significant association using Venice criteria and a false-positive report probability (FPRP) test. We constructed functional annotations for these variants using data from the Encyclopedia of DNA Elements Project. We used FPRP to find additional noteworthy associations between 278 SNPs in 117 miRNAs and risk of 26 cancers based on each SNP with one data source. Sixteen SNPs were statistically associated with risk of 17 cancers. We graded the cumulative epidemiological evidence as strong for statistical associations between 10 SNPs in 8 miRNAs and risk of 11 cancers, moderate for 9 SNPs with 12 cancers and weak for 11 SNPs with 11 cancers. Bioinformatics analysis suggested that the SNPs with strong evidence might fall in putative functional regions. In addition, 38 significant associations were observed in 38 SNPs and risk of 13 cancers. This study offered a comprehensive research on miRNA gene variants and cancer risk and provided referenced information for the genetic predisposition to cancer risk in future research.
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Affiliation(s)
- Jie Tian
- Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, China
| | - Yingxian Dong
- Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, China
| | - Shuai Chang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, China
| | - Yan Wang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, China
| | - Cheng Shen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, China
| | - Guowei Che
- Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, China
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Yi C, Li J, Xin Q, Shan S, Ding E, Jin M, Li B, Li J, Liu Q. Association of microRNA polymorphisms with gastric cancer risk in the North Chinese Han population. J Cancer Res Ther 2022; 18:581-586. [DOI: 10.4103/jcrt.jcrt_74_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Abstract
Since their first discovery more than 20 years ago, miRNAs have been subject to deliberate research and analysis for revealing their physiological or pathological involvement. Regulatory roles of miRNAs in signal transduction, gene expression, and cellular processes in development, differentiation, proliferation, apoptosis, and homeostasis also imply their critical role in disease pathogenesis. Their roles in cancer, neurodegenerative diseases, and other systemic diseases have been studied broadly. In these regulatory pathways, their mutations and target sequence variations play critical roles to determine their functional repertoire. In this chapter, we summarize studies that investigated the role of mutations, polymorphisms, and other variations of miRNAs in respect to pathological processes.
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16
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Jiménez-Morales S, Núñez-Enríquez JC, Cruz-Islas J, Bekker-Méndez VC, Jiménez-Hernández E, Medina-Sanson A, Olarte-Carrillo I, Martínez-Tovar A, Flores-Lujano J, Ramírez-Bello J, Pérez-Saldívar ML, Martín-Trejo JA, Pérez-Lorenzana H, Amador-Sánchez R, Mora-Ríos FG, Peñaloza-González JG, Duarte-Rodríguez DA, Torres-Nava JR, Flores-Bautista JE, Espinosa-Elizondo RM, Román-Zepeda PF, Flores-Villegas LV, Tamez-Gómez EL, López-García VH, Lara-Ramos JR, González-Ulivarri JE, Martínez-Silva SI, Espinoza-Anrubio G, Almeida-Hernández C, Ramírez-Colorado R, Hernández-Mora L, García-López LR, Cruz-Ojeda GA, Godoy-Esquivel AE, Contreras-Hernández I, Medina-Hernández A, López-Caballero MG, Hernández-Pineda NA, Granados-Kraulles J, Rodríguez-Vázquez MA, Torres-Valle D, Cortés-Reyes C, Medrano-López F, Pérez-Gómez JA, Martínez-Ríos A, Aguilar-De-Los-Santos A, Serafin-Díaz B, Gutiérrez-Rivera MDL, Merino-Pasaye LE, Vargas-Alarcón G, Mata-Rocha M, Sepúlveda-Robles OA, Rosas-Vargas H, Hidalgo-Miranda A, Mejía-Aranguré JM. Association Analysis Between the Functional Single Nucleotide Variants in miR-146a, miR-196a-2, miR-499a, and miR-612 With Acute Lymphoblastic Leukemia. Front Oncol 2021; 11:762063. [PMID: 34804964 PMCID: PMC8602911 DOI: 10.3389/fonc.2021.762063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/12/2021] [Indexed: 01/26/2023] Open
Abstract
Background Acute lymphoblastic leukemia (ALL) is characterized by an abnormal proliferation of immature lymphocytes, in whose development involves both environmental and genetic factors. It is well known that single nucleotide polymorphisms (SNPs) in coding and noncoding genes contribute to the susceptibility to ALL. This study aims to determine whether SNPs in miR-146a, miR-196a-2, miR-499a, and miR-612 genes are associated with the risk to ALL in pediatric Mexican population. Methods A multicenter case-control study was carried out including patients with de novo diagnosis of ALL and healthy subjects as control group. The DNA samples were obtained from saliva and peripheral blood, and the genotyping of rs2910164, rs12803915, rs11614913, and rs3746444 was performed using the 5′exonuclease technique. Gene-gene interaction was evaluated by the multifactor dimensionality reduction (MDR) software. Results miR-499a rs3746444 showed significant differences among cases and controls. The rs3746444G allele was found as a risk factor to ALL (OR, 1.6 [95% CI, 1.05–2.5]; p = 0.028). The homozygous GG genotype of rs3746444 confers higher risk to ALL than the AA genotype (OR, 5.3 [95% CI, 1.23–23.4]; p = 0.01). Moreover, GG genotype highly increases the risk to ALL in male group (OR, 17.6 [95% CI, 1.04–298.9]; p = 0.00393). In addition, an association in a gender-dependent manner among SNPs located in miR-146a and miR-196a-2 genes and ALL susceptibility was found. Conclusion Our findings suggest that SNP located in miR-499a, miR-146a, and miR-196a-2 genes confer risk to ALL in Mexican children. Experimental analysis to decipher the role of these SNPs in human hematopoiesis could improve our understanding of the molecular mechanism underlying the development of ALL.
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Affiliation(s)
- Silvia Jiménez-Morales
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Juan Carlos Núñez-Enríquez
- Unidad de Investigación Médica en Epidemiología Clínica, Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional "Siglo XXI", Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
| | - Jazmín Cruz-Islas
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Vilma Carolina Bekker-Méndez
- Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología "Dr. Daniel Méndez Hernández", "La Raza", IMSS, Mexico City, Mexico
| | - Elva Jiménez-Hernández
- Servicio de Hematología Pediátrica, Hospital General "Gaudencio González Garza", Centro Médico Nacional "La Raza", IMSS, Mexico City, Mexico
| | - Aurora Medina-Sanson
- Departamento de Hemato-Oncología, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
| | - Irma Olarte-Carrillo
- Servicio de Hematología, Departamento de Investigación, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
| | - Adolfo Martínez-Tovar
- Servicio de Hematología, Departamento de Investigación, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
| | - Janet Flores-Lujano
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Julian Ramírez-Bello
- Departamento de Endocrinología, Instituto Nacional de Cardiología, Ignacio Chávez, México City, Mexico
| | | | - Jorge Alfonso Martín-Trejo
- Servicio de Hematología Pediátrica Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional "Siglo XXI", IMSS, Mexico City, Mexico
| | - Héctor Pérez-Lorenzana
- Servicio de Cirugía Pediátrica, Hospital General "Gaudencio González Garza", Centro Médico Nacional (CMN) "La Raza", IMSS, Mexico City, Mexico
| | - Raquel Amador-Sánchez
- Servicio de Hematología Pediátrica, Hospital General Regional "Carlos McGregor Sánchez Navarro", IMSS, Mexico City, Mexico
| | - Felix Gustavo Mora-Ríos
- Cirugía Pediátrica, Hospital Regional "General Ignacio Zaragoza", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Mexico City, Mexico
| | | | | | - José Refugio Torres-Nava
- Servicio de Oncología, Hospital Pediátrico de Moctezuma, Secretaría de Salud de la Ciudad de México (SSCDMX), Mexico City, Mexico
| | | | | | - Pedro Francisco Román-Zepeda
- Coordinación Clínica y Servicio de Cirugía Pediátrica, Hospital General Regional (HGR) No. 1 "Dr. Carlos Mac Gregor Sánchez Navarro", IMSS, Mexico City, Mexico
| | | | | | | | | | | | | | - Gilberto Espinoza-Anrubio
- Servicio de Pediatría, Hospital General Zona (HGZ) No. 8 "Dr. Gilberto Flores Izquierdo" IMSS, Mexico City, Mexico
| | - Carolina Almeida-Hernández
- Jefatura de Enseñanza, Hospital General de Ecatepec "Las Américas", Instituto de Salud del Estado de México (ISEM), Mexico City, Mexico
| | | | - Luis Hernández-Mora
- Jefatura de Enseñanza, Hospital Pediátrico San Juan de Aragón, Secretaría de Salud (SS), Mexico City, Mexico
| | | | | | | | | | | | | | | | | | | | - Delfino Torres-Valle
- Coordinación Clínica y Pediatría del Hospital General de Zona 71, IMSS, Mexico City, Mexico
| | - Carlos Cortés-Reyes
- Pediatría, Hospital General Dr. Darío Fernández Fierro, ISSSTE, Mexico City, Mexico
| | - Francisco Medrano-López
- Coordinación Clínica y Servicio de Pediatría, HGR No. 72 "Dr. Vicente Santos Guajardo", IMSS, Mexico City, Mexico
| | - Jessica Arleet Pérez-Gómez
- Coordinación Clínica y Servicio de Pediatría, HGR No. 72 "Dr. Vicente Santos Guajardo", IMSS, Mexico City, Mexico
| | - Annel Martínez-Ríos
- Cirugía Pediátrica del Hospital Regional "General Ignacio Zaragoza", ISSSTE, Mexico City, Mexico
| | | | - Berenice Serafin-Díaz
- Coordinación Clínica y Pediatría del Hospital General de Zona 57, IMSS, Mexico City, Mexico
| | - María de Lourdes Gutiérrez-Rivera
- Servicio de Oncología Pediátrica Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría "Dr. Silvestre Frenk Freund", IMSS, Mexico City, Mexico
| | | | - Gilberto Vargas-Alarcón
- Departamento of Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | - Minerva Mata-Rocha
- Unidad de Investigación Médica en Genética Humana, Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional "Siglo XXI", IMSS, Mexico City, Mexico
| | - Omar Alejandro Sepúlveda-Robles
- Unidad de Investigación Médica en Genética Humana, Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional "Siglo XXI", IMSS, Mexico City, Mexico
| | - Haydeé Rosas-Vargas
- Unidad de Investigación Médica en Genética Humana, Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional "Siglo XXI", IMSS, Mexico City, Mexico
| | - Alfredo Hidalgo-Miranda
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Juan Manuel Mejía-Aranguré
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.,Unidad de Investigación Médica en Genética Humana, Unidad Medica de Alta Especialidad (UMAE) Hospital de Pediatría "Dr. Silvestre Frenk Freund", Centro Médico Nacional "Siglo XXI", IMSS, Mexico City, Mexico.,Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
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Mirahmadi Y, Nabavi R, Taheri F, Samadian MM, Ghale-Noie ZN, Farjami M, Samadi-khouzani A, Yousefi M, Azhdari S, Salmaninejad A, Sahebkar A. MicroRNAs as Biomarkers for Early Diagnosis, Prognosis, and Therapeutic Targeting of Ovarian Cancer. JOURNAL OF ONCOLOGY 2021; 2021:3408937. [PMID: 34721577 PMCID: PMC8553480 DOI: 10.1155/2021/3408937] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/27/2021] [Indexed: 02/06/2023]
Abstract
Ovarian cancer is the major cause of gynecologic cancer-related mortality. Regardless of outstanding advances, which have been made for improving the prognosis, diagnosis, and treatment of ovarian cancer, the majority of the patients will die of the disease. Late-stage diagnosis and the occurrence of recurrent cancer after treatment are the most important causes of the high mortality rate observed in ovarian cancer patients. Unraveling the molecular mechanisms involved in the pathogenesis of ovarian cancer may help find new biomarkers and therapeutic targets for ovarian cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression, mostly at the posttranscriptional stage, through binding to mRNA targets and inducing translational repression or degradation of target via the RNA-induced silencing complex. Over the last two decades, the role of miRNAs in the pathogenesis of various human cancers, including ovarian cancer, has been documented in multiple studies. Consequently, these small RNAs could be considered as reliable markers for prognosis and early diagnosis. Furthermore, given the function of miRNAs in various cellular pathways, including cell survival and differentiation, targeting miRNAs could be an interesting approach for the treatment of human cancers. Here, we review our current understanding of the most updated role of the important dysregulation of miRNAs and their roles in the progression and metastasis of ovarian cancer. Furthermore, we meticulously discuss the significance of miRNAs as prognostic and diagnostic markers. Lastly, we mention the opportunities and the efforts made for targeting ovarian cancer through inhibition and/or stimulation of the miRNAs.
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Affiliation(s)
- Yegane Mirahmadi
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Fourough Taheri
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Mohammad Mahdi Samadian
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zari Naderi Ghale-Noie
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahsa Farjami
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abbas Samadi-khouzani
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Meysam Yousefi
- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sara Azhdari
- Department of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Arash Salmaninejad
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Genetics, Faculty of Medicine, Guilan University of Medical Sciences, Guilan, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Liu F, Wang S, Luo Z. Associations of the miRNA-146a rs2910164 and the miRNA-499a rs3746444 Polymorphisms With Plasma Lipid Levels: A Meta-Analysis. Front Genet 2021; 12:746686. [PMID: 34646311 PMCID: PMC8503190 DOI: 10.3389/fgene.2021.746686] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 08/24/2021] [Indexed: 12/02/2022] Open
Abstract
Background: The studies of miRNAs are vibrant and remain at the forefront in the cardiovascular system. Emerging studies indicate that the genetic polymorphisms of the miRNA gene may affect lipid metabolism; this study aims to clarify the specific correlations between the rs2910164 and rs3746444 polymorphisms and lipid levels. Methods and Results: A comprehensive search of literature was performed from December 31, 2020, to May 31, 2021, by searching of the PubMed and the Cochrane databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the differences in lipid levels between the genotypes. rs2910164, a functional polymorphism in the miRNA-146a gene, was associated with increased triglycerides (TG) (SMD = 0.35, 95% CI = 0.15-0.54, p < 0.001), total cholesterol (TC) (SMD = 0.43, 95% CI = 0.16-0.70, p < 0.001), and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.37, 95% CI = 0.11-0.63, p = 0.01) as well as decreased high-density lipoprotein cholesterol (HDL-C) (SMD = -0.27, 95% CI = -0.47-0.07, p = 0.01) levels. rs3746444, a functional polymorphism in the miRNA-499a gene, was only correlated with decreased TG (SMD = -0.09, 95% CI = -0.17-0.01, P = 0.03) levels. Conclusions: The miRNA-146a rs2910164 polymorphism is significantly associated with atherogenic dyslipidemia.
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Affiliation(s)
- Fuqiang Liu
- Department of Cardiology, First People's Hospital of Chengdu, Chengdu, China
| | - Shengping Wang
- Department of Cardiology, First People's Hospital of Chengdu, Chengdu, China
| | - Zhi Luo
- Department of Internal Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
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Tommasi C, Pellegrino B, Boggiani D, Sikokis A, Michiara M, Uliana V, Bortesi B, Bonatti F, Mozzoni P, Pinelli S, Squadrilli A, Viani MV, Cassi D, Maglietta G, Meleti M, Musolino A. Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers. Front Oncol 2021; 11:700853. [PMID: 34552867 PMCID: PMC8450578 DOI: 10.3389/fonc.2021.700853] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 08/20/2021] [Indexed: 12/20/2022] Open
Abstract
Women with pathogenic germline mutations in BRCA1 and BRCA2 genes have an increased risk to develop breast and ovarian cancer. There is, however, a high interpersonal variability in the modality and timing of tumor onset in those subjects, thus suggesting a potential role of other individual’s genetic, epigenetic, and environmental risk factors in modulating the penetrance of BRCA mutations. MicroRNAs (miRNAs) are small noncoding RNAs that can modulate the expression of several genes involved in cancer initiation and progression. MiRNAs are dysregulated at all stages of breast cancer and although they are accessible and evaluable, a standardized method for miRNA assessment is needed to ensure comparable data analysis and accuracy of results. The aim of this review was to highlight the role of miRNAs as potential biological markers for BRCA mutation carriers. In particular, biological and clinical implications of a link between lifestyle and nutritional modifiable factors, miRNA expression and germline BRCA1 and BRCA2 mutations are discussed with the knowledge of the best available scientific evidence.
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Affiliation(s)
- Chiara Tommasi
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,Department of Medicine and Surgery, University of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Benedetta Pellegrino
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,Department of Medicine and Surgery, University of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Daniela Boggiani
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Angelica Sikokis
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Maria Michiara
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - Vera Uliana
- Medical Genetics Unit, University Hospital of Parma, Parma, Italy
| | - Beatrice Bortesi
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Francesco Bonatti
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - Paola Mozzoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Silvana Pinelli
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Anna Squadrilli
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - Maria Vittoria Viani
- Dental School, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Diana Cassi
- Unit of Dentistry and Oral-Maxillo-Facial Surgery, Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Giuseppe Maglietta
- GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy.,Research and Innovation Unit, University Hospital of Parma, Parma, Italy
| | - Marco Meleti
- Dental School, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Antonino Musolino
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,Department of Medicine and Surgery, University of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
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Massignam ET, Dieter C, Pellenz FM, Assmann TS, Crispim D. Involvement of miR-126 rs4636297 and miR-146a rs2910164 polymorphisms in the susceptibility for diabetic retinopathy: a case-control study in a type 1 diabetes population. Acta Ophthalmol 2021; 99:e461-e469. [PMID: 33124182 DOI: 10.1111/aos.14638] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 08/20/2020] [Accepted: 09/08/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND PURPOSE MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. MiRNA-126 and miRNA-146a have been described as having abnormal expressions in diabetic retinopathy (DR) patients. Polymorphisms in genes codifying miRNAs (miRSNPs) may alter the expression of the corresponding miRNA and, thus, interfere with susceptibility to DR. Therefore, miRSNPs in miR-126 and miR-146a genes could be associated with DR susceptibility. The purpose of this study was to investigate the association between miR-126 rs4636297 (G/A) and miR-146a rs2910164 (G/C) miRSNPs and DR. METHODS This case-control study included 195 type 1 diabetes mellitus (T1DM) patients with DR (cases) and 215 patients without DR and with ≥10 years of T1DM (controls). MiRSNPs were genotyped by real-time PCR. RESULTS Genotype distributions of two analysed miRSNPs were in Hardy-Weinberg equilibrium in controls (p > 0.050). Frequencies of the miR-126 rs4636297 miRSNP were not significantly different between case and control groups (p = 0.169). However, after adjustment for age, glycated haemoglobin, triglycerides, estimated glomerular filtration rate and ethnicity, the A allele of this miRSNP was associated with protection for DR under additive [OR: 0.444 (95% CI: 0.211-0.936), p = 0.033] and dominant [OR: 0.512 (95% CI: 0.303-0.865), p = 0.012] inheritance models. Genotype and allele frequencies of miR-146a rs2910164 miRSNP did not differ between groups (p = 0.368 and p = 0.957), and this polymorphism was not associated with DR when assuming different inheritance models. CONCLUSION Our results suggest an association between the A allele of miR-126 rs4636297 miRSNP and protection for DR in a Southern Brazilian population.
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Affiliation(s)
- Eloísa Toscan Massignam
- Endocrine Division Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
- Graduate Program in Medical Sciences: Endocrinology Faculty of Medicine Department of Internal Medicine Universidade Federal do Rio Grande do Sul Porto Alegre Brazil
| | - Cristine Dieter
- Endocrine Division Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
- Graduate Program in Medical Sciences: Endocrinology Faculty of Medicine Department of Internal Medicine Universidade Federal do Rio Grande do Sul Porto Alegre Brazil
| | - Felipe Mateus Pellenz
- Endocrine Division Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
- Graduate Program in Medical Sciences: Endocrinology Faculty of Medicine Department of Internal Medicine Universidade Federal do Rio Grande do Sul Porto Alegre Brazil
| | - Taís Silveira Assmann
- Endocrine Division Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
- Graduate Program in Medical Sciences: Endocrinology Faculty of Medicine Department of Internal Medicine Universidade Federal do Rio Grande do Sul Porto Alegre Brazil
| | - Daisy Crispim
- Endocrine Division Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
- Graduate Program in Medical Sciences: Endocrinology Faculty of Medicine Department of Internal Medicine Universidade Federal do Rio Grande do Sul Porto Alegre Brazil
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21
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Pawlina-Tyszko K, Semik-Gurgul E, Gurgul A, Oczkowicz M, Szmatoła T, Bugno-Poniewierska M. Application of the targeted sequencing approach reveals the single nucleotide polymorphism (SNP) repertoire in microRNA genes in the pig genome. Sci Rep 2021; 11:9848. [PMID: 33972633 PMCID: PMC8110958 DOI: 10.1038/s41598-021-89363-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 04/21/2021] [Indexed: 12/26/2022] Open
Abstract
MicroRNAs (miRNAs) are recognized as gene expression regulators, indirectly orchestrating a plethora of biological processes. Single nucleotide polymorphism (SNP), one of the most common genetic variations in the genome, is established to affect miRNA functioning and influence complex traits and diseases. SNPs in miRNAs have also been associated with important production traits in livestock. Thus, the aim of our study was to reveal the SNP variability of miRNA genes in the genome of the pig, which is a significant farm animal and large-mammal human model. To this end, we applied the targeted sequencing approach, enabling deep sequencing of specified genomic regions. As a result, 73 SNPs localized in 50 distinct pre-miRNAs were identified. In silico analysis revealed that many of the identified SNPs influenced the structure and energy of the hairpin precursors. Moreover, SNPs localized in the seed regions were shown to alter targeted genes and, as a result, enrich different biological pathways. The obtained results corroborate a significant impact of SNPs on the miRNA processing and broaden the state of knowledge in the field of animal genomics. We also report the targeted sequencing approach to be a promising alternative for the whole genome sequencing in miRNA genes focused studies.
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Affiliation(s)
- Klaudia Pawlina-Tyszko
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1, Balice, 32-083, Kraków, Poland.
| | - Ewelina Semik-Gurgul
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1, Balice, 32-083, Kraków, Poland
| | - Artur Gurgul
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1, Balice, 32-083, Kraków, Poland
- Center for Experimental and Innovative Medicine, The University of Agriculture in Kraków, Rędzina 1c, 30-248, Kraków, Poland
| | - Maria Oczkowicz
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1, Balice, 32-083, Kraków, Poland
| | - Tomasz Szmatoła
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1, Balice, 32-083, Kraków, Poland
- Center for Experimental and Innovative Medicine, The University of Agriculture in Kraków, Rędzina 1c, 30-248, Kraków, Poland
| | - Monika Bugno-Poniewierska
- Department of Animal Reproduction, Anatomy and Genomics, The University of Agriculture in Kraków, al. Mickiewicza 24/28, 30-059, Kraków, Poland
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22
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Khan MS, Rahman B, Haq TU, Jalil F, Khan BM, Maodaa SN, Al-Farraj SA, El-Serehy HA, Shah AA. Deciphering the Variants Located in the MIR196A2, MIR146A, and MIR423 with Type-2 Diabetes Mellitus in Pakistani Population. Genes (Basel) 2021; 12:genes12050664. [PMID: 33925232 PMCID: PMC8146332 DOI: 10.3390/genes12050664] [Citation(s) in RCA: 4] [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: 02/27/2021] [Revised: 04/07/2021] [Accepted: 04/09/2021] [Indexed: 12/22/2022] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that control the post-transcriptional gene expression. They play a pivotal role in the regulation of important physiological processes. Variations in miRNA genes coding for mature miRNA sequences have been implicated in several diseases. However, the association of variants in miRNAs genes with Type 2 Diabetes Mellitus (T2DM) in the Pakistani population is rarely reported. Therefore, the current study was designed to investigate the association of rs11614913 T/C (MIR196A2), rs2910164 G/C (MIR146A), and rs6505162 C/A (MIR423) in clinicopathological proven T2DM patients and gender-matched healthy controls. The tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR) reaction method was used to determine the genotypes and to establish the association of each variant with T2DM through inherited models. In conclusion, the present study showed that variants rs11614913 T/C and rs2910164 G/C were linked with the risk of T2DM. The data suggested that rs11614913 T/C and rs2910164 G/C could be considered as novel risk factors in the pathogenesis of T2DM in the Pakistani population.
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Affiliation(s)
- Muhammad Sohail Khan
- Department of Biotechnology, University of Malakand, Chakdara 18800, Pakistan; (M.S.K.); (B.R.); (T.U.H.)
| | - Bashir Rahman
- Department of Biotechnology, University of Malakand, Chakdara 18800, Pakistan; (M.S.K.); (B.R.); (T.U.H.)
| | - Taqweem Ul Haq
- Department of Biotechnology, University of Malakand, Chakdara 18800, Pakistan; (M.S.K.); (B.R.); (T.U.H.)
| | - Fazal Jalil
- Department of Biotechnology, Abdul Wali Khan University Mardan (AWKUM), Mardan 23200, Pakistan;
| | - Bilal Muhammad Khan
- University Institute of Biochemistry and Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan;
- National Center of Industrial Biotechnology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46300, Pakistan
| | - Saleh N. Maodaa
- Department of Zoology, College of Science, King Saud University, Riyadh l1451, Saudi Arabia; (S.N.M.); (S.A.A.-F.); (H.A.E.-S.)
| | - Saleh A. Al-Farraj
- Department of Zoology, College of Science, King Saud University, Riyadh l1451, Saudi Arabia; (S.N.M.); (S.A.A.-F.); (H.A.E.-S.)
| | - Hamed A. El-Serehy
- Department of Zoology, College of Science, King Saud University, Riyadh l1451, Saudi Arabia; (S.N.M.); (S.A.A.-F.); (H.A.E.-S.)
| | - Aftab Ali Shah
- Department of Biotechnology, University of Malakand, Chakdara 18800, Pakistan; (M.S.K.); (B.R.); (T.U.H.)
- Correspondence:
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Liu J, Dong P, Zhou L, Wang S. The Association between Five Genetic Variants in MicroRNAs (rs2910164, rs11614913, rs3746444, rs11134527, and rs531564) and Cervical Cancer Risk: A Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9180874. [PMID: 33816633 PMCID: PMC7987420 DOI: 10.1155/2021/9180874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 01/17/2021] [Accepted: 02/15/2021] [Indexed: 12/28/2022]
Abstract
The objective of this study was to conduct a meta-analysis to systematically summarize and investigate the association of miRNA-124 rs531564, miRNA-218 rs11134527, miRNA-146a rs2910164, miRNA-196a2 rs11614913, and miRNA-499 rs3746444 polymorphisms with cervical cancer. A systematic review was performed to identify relevant studies using Embase and PubMed databases. A chi-square-based Q-test combined with the inconsistency index (I 2) was used to check the heterogeneity between studies. A total of six case-control studies on rs2910164 and rs11614913, 4 studies on rs3746444 and rs11134527, and three studies on rs531564 were included. No evidence of association was found between miR-146a rs2910164, miR-196a2 rs11614913, miRNA-499 rs3746444, and miR-218 rs11134527 polymorphisms and cervical cancer risk in all the genetic models. The miR-124 rs531564 polymorphism was associated with a statistically increased risk of cervical cancer in a homozygote model (CC vs. GG: OR = 2.87, 95% CI: 1.40-5.91, P H = 0.887), dominant model (GC/CC vs. GG: OR = 1.38, 95% CI: 1.07-1.80, P H = 0.409), and recessive model (CC vs. GC/GG: OR = 2.26, 95% CI: 1.58-3.23, P H = 0.979). However, this finding should be interpreted with caution for limited samples and heterogeneity. Large-scale and well-designed studies are needed to validate our result.
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Affiliation(s)
- Jia Liu
- Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Peng Dong
- Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Liane Zhou
- Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Shijun Wang
- Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University, Beijing, China
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Carotid Intima-Media Thickness, Genetic Risk, and Ischemic Stroke: A Family-Based Study in Rural China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 18:ijerph18010119. [PMID: 33375320 PMCID: PMC7795493 DOI: 10.3390/ijerph18010119] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/16/2020] [Accepted: 12/21/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND Carotid intima-media thickness (cIMT) has been associated with an elevated risk of ischemic stroke (IS) in several studies, but the results are inconsistent. We investigated whether the association between cIMT and IS varied across different IS subtypes, and further assessed gene-cIMT interactions' association with IS risk. METHODS A total of 1048 IS cases (795 large-artery atherosclerosis (LAA) cases, 103 small-vessel occlusion (SVO) cases, and 150 other subtypes) and 2696 IS-free controls across 2179 families were included in the analysis. Self-reported IS cases were confirmed through medical records' review and head imaging by computed tomography and/or magnetic resonance imaging. The mean values of the common cIMT obtained in bilateral distal and proximal carotid artery segments were used. The genotype information of rs2910164 polymorphism in microRNA-146a (miR-146a) was also collected. RESULTS We found that cIMT was significantly associated with a higher risk of IS and LAA subtype but not SVO subtype in the multivariate-adjusted models. The odds ratio (OR) and 95% confidence interval (CI) in the highest quartile versus the lowest quartile of cIMT was 2.48 (1.92-3.20) for IS and 2.75 (2.08-3.64) for LAA (both p trend <0.001). The results also showed that there was a significant interaction between cIMT and rs2910164 genotype with the risk of IS (p interaction = 0.03) and LAA (p interaction = 0.02). The associations of cIMT with IS and LAA were strengthened among participants carried rs2910164_GG genotype compared with those with rs2910164_CC genotype. CONCLUSIONS Our results indicate that higher cIMT levels were significantly associated with IS and LAA subtype but not SVO subtype, and the relations were modified by rs2910164 polymorphism in miR-146a.
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Ayadilord M, Tavakoli T, Fakharian T, Soltaninejad E, Naseri M. Relationship analysis of the miR-196a2 polymorphism (rs11614913) with colorectal cancer risk in southern Khorasan, eastern Iran. Meta Gene 2020; 26:100813. [DOI: 10.1016/j.mgene.2020.100813] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma. Radiol Oncol 2020; 54:429-436. [PMID: 33085641 PMCID: PMC7585336 DOI: 10.2478/raon-2020-0057] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 08/06/2020] [Indexed: 02/07/2023] Open
Abstract
Background Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13–0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14–0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28–0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions Our findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.
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NGUYEN TTN, TRAN MTH, NGUYEN VTL, NGUYEN UDP, NGUYEN GDT, HUYNH LH, NGUYEN HT. Single nucleotide polymorphisms in microRNAs action as biomarkers for breast cancer. Turk J Biol 2020; 44:284-294. [PMID: 33110366 PMCID: PMC7585164 DOI: 10.3906/biy-2004-78] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 06/10/2020] [Indexed: 12/16/2022] Open
Abstract
MicroRNAs (miRNAs) have been recently described as small noncoding RNAs that are involved in numerous crucial physiological processes, such as cell cycles, differentiation, development, and metabolism. Thus, dysregulation of these molecules could lead to several severe disorders, including breast cancer (BC). Ongoing investigations in malignant growth diagnostics have distinguished miRNAs as promising disease biomarkers. As with any other mRNAs, single nucleotide polymorphisms (SNPs) in DNA sequence encoding for miRNA (miR-SNPs) indeed lead to potential changes in the function of miRNA. In this study, miR-SNPs located in different miRNA sequence regions, which have been associated with BC in different ways, and the potential mechanisms of how these miR-SNPs develop the risk of the disease were discussed.
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Affiliation(s)
- Thanh Thi Ngoc NGUYEN
- Department of Physiology and Animal Biotechnology, Faculty of Biology and Biotechnology, University of Science, Ho Chi Minh CityVietnam
- Vietnam National University, Ho Chi Minh CityVietnam
| | - Minh Thi Hong TRAN
- Department of Physiology and Animal Biotechnology, Faculty of Biology and Biotechnology, University of Science, Ho Chi Minh CityVietnam
- Vietnam National University, Ho Chi Minh CityVietnam
| | - Vy Thi Lan NGUYEN
- Department of Physiology and Animal Biotechnology, Faculty of Biology and Biotechnology, University of Science, Ho Chi Minh CityVietnam
- Vietnam National University, Ho Chi Minh CityVietnam
| | - Uyen Doan Phuong NGUYEN
- Department of Physiology and Animal Biotechnology, Faculty of Biology and Biotechnology, University of Science, Ho Chi Minh CityVietnam
- Vietnam National University, Ho Chi Minh CityVietnam
| | - Giang Dien Thanh NGUYEN
- Department of Physiology and Animal Biotechnology, Faculty of Biology and Biotechnology, University of Science, Ho Chi Minh CityVietnam
- Vietnam National University, Ho Chi Minh CityVietnam
| | - Luan Huu HUYNH
- Department of Physiology and Animal Biotechnology, Faculty of Biology and Biotechnology, University of Science, Ho Chi Minh CityVietnam
- Vietnam National University, Ho Chi Minh CityVietnam
| | - Hue Thi NGUYEN
- Department of Physiology and Animal Biotechnology, Faculty of Biology and Biotechnology, University of Science, Ho Chi Minh CityVietnam
- Vietnam National University, Ho Chi Minh CityVietnam
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Yang J, Bahcecioglu G, Zorlutuna P. The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment. Bioengineering (Basel) 2020; 7:E124. [PMID: 33050609 PMCID: PMC7712041 DOI: 10.3390/bioengineering7040124] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 10/06/2020] [Accepted: 10/08/2020] [Indexed: 12/18/2022] Open
Abstract
Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes.
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Affiliation(s)
- Jun Yang
- Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA;
| | - Gokhan Bahcecioglu
- Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA;
| | - Pinar Zorlutuna
- Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA;
- Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA;
- Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA
- Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA
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Zhu Y, Lin A, Zheng Y, Xie X, He Q, Zhong W. miR-100 rs1834306 A>G Increases the Risk of Hirschsprung Disease in Southern Chinese Children. PHARMACOGENOMICS & PERSONALIZED MEDICINE 2020; 13:283-288. [PMID: 32848443 PMCID: PMC7428404 DOI: 10.2147/pgpm.s265730] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 07/27/2020] [Indexed: 12/18/2022]
Abstract
Background Hirschsprung disease (HSCR) is a rare congenital gastrointestinal disease characterized by the absence of intestinal submucosal and myometrial ganglion cells. Recently, researches indicated that miR-100 regulated the growth, differentiation and apoptosis of neurons, and affected the functions of HSCR-associated pathways. While miR-100 rs1834306 A>G polymorphism was shown to modify the susceptibility to tumors, the association between this polymorphism and HSCR susceptibility is still unknown. Methods This was a case-control study consisting of 1470 HSCR cases and 1473 controls from southern China. DNA was genotyped by TaqMan real-time PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as statistical indicators. Results We found that miR-100 rs1834306 G allele and GG genotype significantly increased HSCR susceptibility (GG vs AA: adjusted OR=1.31, 95% CI=1.04-1.64, P=0.020; G vs A: adjusted OR=1.12, 95% CI=1.01-1.25, P=0.041; GG vs AA/AG: adjusted OR=1.30, 95% CI=1.07-1.59, P=0.010). In the stratified analysis, miR-100 rs1834306 GG genotype carriers had higher risk to develop HSCR in all clinical subtypes when compared with those with AA/AG genotypes, and OR was rising with HSCR aggravation (SHSCR: adjusted OR=1.28, 95% CI=1.03-1.59, P=0.029; LHSCR: adjusted OR=1.48, 95% CI=1.06-2.07, P=0.020; TCA: adjusted OR=2.12, 95% CI=1.22-3.69, P=0.008). Conclusion Our findings suggested that miR-100 rs1834306 A>G polymorphism was associated with increased HSCR susceptibility in southern Chinese children. Furthermore, miR-100 rs1834306 GG genotype had a greater genetic pathopoiesis in severe HSCR.
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Affiliation(s)
- Yun Zhu
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China
| | - Ao Lin
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China
| | - Yi Zheng
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China
| | - Xiaoli Xie
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China
| | - Qiuming He
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China
| | - Wei Zhong
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China
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Bahreini F, Rayzan E, Rezaei N. microRNA-related single-nucleotide polymorphisms and breast cancer. J Cell Physiol 2020; 236:1593-1605. [PMID: 32716070 DOI: 10.1002/jcp.29966] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 07/13/2020] [Indexed: 12/15/2022]
Abstract
Breast cancer, as the most common cancer in women which affects patients both mentally and physically, requires great attention in many areas and many levels as this cancer is known to be multifactorial. Single-stranded molecules called microRNAs with near 22 nucleotides are seen to act in central dogma of molecular biology by inhibiting the translation process; it is demonstrated that any alteration in their sequence especially single-nucleotide polymorphisms (SNPs) may lead into increasing the breast cancer risk. miR-SNPs are considered to be the potential biomarkers for early detection of breast cancer. As a result, this review documents the well-known miR-SNPs that are known to be associated with breast cancer. In this regard, two principals were discussed: (a) SNPs in the target genes of microRNAs and the alteration in gene expression due to this phenomenon; (b) changes based on the SNPs in the microRNA coding region and the impact on their interaction with target messenger RNA.
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Affiliation(s)
- Farbod Bahreini
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Elham Rayzan
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- International Hematology/Oncology of Pediatrics Experts, Universal Scientific Education and Research Network, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity, Universal Scientific Education and Research Network, Tehran, Iran
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Santos JSD, Zunta GL, Negrini AB, Ribeiro MSG, Martinez CAR, Ribeiro ML, Lourenço GJ, Ortega MM. The association of a single-nucleotide variant in the microRNA-146a with advanced colorectal cancer prognosis. Tumour Biol 2020; 42:1010428320923856. [PMID: 32438863 DOI: 10.1177/1010428320923856] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The aim of this study was to evaluate the association of single-nucleotide variant n.60G>C (rs2910164) of microRNA (miR)-146a, related to suppressing of BRCA1/2 DNA repair protein, with the risk and survival of colorectal cancer patients, as well as miR-146a and BRCA1/2 levels and miR binding efficiency. The genotypes were identified in 125 colorectal cancer patients and 276 controls using TaqMan polymerase chain reaction assay. The miR-146a and BRCA1/2 levels were assessed by quantitative-polymerase chain reaction protocols. Primary precursor of miR-146a containing G (wild-type) and C (variant) allele were cloned into pcDNA.3.3 vector and co-transfected in HT-29 colorectal cancer cell line. Luciferase reporter assay was performed to assess miR-146a binding to BRCA2 3'-untranslated region in HT-29. The differences between groups were calculated using chi-square or Fisher's exact test, logistic regression, and Mann-Whitney test. The prognostic impact of single-nucleotide variant genotypes on overall survival was evaluated by Kaplan-Meier estimate and Cox regression. The GC or CC genotypes prevalence was similar in patients and controls (50.4% vs 50.7%, p = 0.74). However, patients with tumors in advanced stage with miR-146a GG genotype had 2.41 more chance of dying than GC or CC genotypes. In addition, tumor tissues of patients with GG genotype presented higher miR-146a (p = 0.02) and lower BRCA1 (p = 0.01) and BRCA2 (p < 0.0001) levels when compared to those with GC or CC genotypes. In fact, pcDNA.3.3-miR-146a-G presented increased binding capacity to the 3'-untranslated region of BRCA2 (p = 0.001) compared to pcDNA.3.3-miR-146a-C. In addition, the G allele altered the binding affinity between miR-146a and its BRCA2 3'-untranslated region target (p < 0.001), thus enhancing suppression of BRCA2 expression. Our results suggest that single-nucleotide variant rs2910164 does not influence the colorectal cancer risk in Brazilian patients; however, the GG genotype could act as a factor of worse prognosis in patients with advanced disease due to suppression of BRCA1/2 modulated by miR-146a.
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Affiliation(s)
- Jéssica Silva Dos Santos
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University (USF), Bragança Paulista, Brazil
| | - Gabriella Lucatto Zunta
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University (USF), Bragança Paulista, Brazil
| | - Amanda Binatto Negrini
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University (USF), Bragança Paulista, Brazil
| | - Marina Silva Guinda Ribeiro
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University (USF), Bragança Paulista, Brazil
| | | | - Marcelo Lima Ribeiro
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University (USF), Bragança Paulista, Brazil
| | - Gustavo Jacob Lourenço
- Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil
| | - Manoela Marques Ortega
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University (USF), Bragança Paulista, Brazil
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Siasi E, Solimani M. Associations of Single Nucleotide Polymorphism in miR-146a Gene with Susceptibility to Breast Cancer in the Iranian Female. Asian Pac J Cancer Prev 2020; 21:1585-1593. [PMID: 32592352 PMCID: PMC7568866 DOI: 10.31557/apjcp.2020.21.6.1585] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 05/07/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs), short regulatory RNAs, function as negative regulators able to modulate gene expression. Just as other genetic variant, single nucleotide polymorphisms (SNPs) in miRNA genes, may have an impact on their expression and/or maturation and hence leading to different consequences in carcinogenesis. Accordingly, this study aimed to assess the frequency of miR-146a G/C (rs2910164) polymorphism and its association with susceptibility to breast cancer in Iranian women. METHODS We conducted a case-control study using Tetra ARMS polymerase chain reaction (Tetra ARMS PCR) method in 100 Iranian female participants (50 breast cancer patients and 50 controls). Besides, a number of sequenced samples were chosen to confirm the accuracy of genotyping by Tetra ARMA PCR. SPSS software was utilized for all statistical analyses. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to analyze the association between the SNP frequency and breast cancer. RESULTS The frequency of genotypes for G/G, G/C, and C/C were 23 (46%), 26 (52%), and 1 (2%) among cases and 15 (30%), 33 (66%), and 2(4%) among controls, respectively. The results generated by the groups did not show any significant correlation between miR-146a G/C (rs2910164) polymorphism and breast cancer, either at genotype or allele levels (P>0.05). F-SNP-based in silico analysis indicated possible modifications in transcriptional regulations induced by miR-146a G/C (rs2910164) variations. CONCLUSION Overall, our results indicated no correlation between miR-146a G/C (rs2910164) polymorphism and genetic susceptibility to breast cancer in Iranian female populations. However, these findings need to be further confirmed by analyses of a larger number of cases.
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Affiliation(s)
- Elham Siasi
- Department of Genetic, Collage of Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
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Abstract
OBJECTIVES Studies have demonstrated that genetic variants in the miRNA-coding genes might be associated with cancer susceptibility and survival. Here, we aimed to investigate the influence of MIR3142HG single-nucleotide polymorphisms on the individual's susceptibility to and patients' prognosis of glioma. MATERIALS AND METHODS Six variants were genotyped by Agena MassARRAY iPLEX Gold assay among 529 glioma patients and 502 healthy controls. Association of MIR3142HG polymorphisms with the risk for and prognosis of glioma was analyzed by logistic regression analysis and Cox proportional hazards model, respectively. RESULTS In the risk analysis, rs17057846 (odds ratio [OR]=1.93, P=0.047), rs2961920 (OR=1.53, P=0.019), and rs58747524 (OR=1.23, P=0.046) polymorphisms were associated with increased glioma risk, while rs7727115 (OR=0.76, P=0.030) and rs1582417 (female individuals, OR=0.49, P=0.017) variants were associated with decreased risk. In the survival analysis, rs1582417 polymorphism (hazard ratio=1.26, P=0.017) contributed to poorer prognosis overall. Rs17057846, rs1582417, and rs2431689 polymorphisms were associated with prognosis of astrocytoma, and rs1582417, rs17057846, and rs58747524 variants were associated with the survival rate in patients with low-grade glioma (I to II). CONCLUSION Our study provided the first evidence for the impact of rs1582417, rs17057846, rs2431689, rs2961920, rs58747524, and rs7727115 polymorphisms in MIR3142HG on the susceptibility to and/or prognosis of glioma in the Chinese Han population.
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Ahmad M, Shah AA. Predictive role of single nucleotide polymorphism (rs11614913) in the development of breast cancer in Pakistani population. Per Med 2020; 17:213-227. [PMID: 32320336 DOI: 10.2217/pme-2019-0086] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Aim: miRNAs play an important role in breast cancer (BC). Variations in miRNAs influence their maturation, expression and consequently regulation of their target genes. Materials & methods: In this study, single nucleotide polymorphism rs11614913 was genotyped in BC patients (n = 300) and 230 controls by employing tetra primer amplification refractory mutation system PCR and Sanger sequencing (Macrogen Korea). Results: A significant difference was observed in the genotypes through co-dominant (χ2.#x00A0;= 42.03; p < 0.0001), additive (odds ratio [OR] = 0.6441 [0.4887-0.8490, 95% confidence interval]; p < 0.0019), dominant (OR = 0.3996 [0.2809-0.5686], p < 0.0001) and recessive (OR = 0.2993 [0.1220-0.7347], p < 0.009) statistical models showed decreased risk association of C allele with BC. Conclusion: Females having CT genotype are at higher risk of BC as compared with those having CC genotype.
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Affiliation(s)
- Mushtaq Ahmad
- Department of Biotechnology, Faculty of Biological Sciences, University of Malakand, Chakdara, Pakistan
| | - Aftab Ali Shah
- Department of Biotechnology, Faculty of Biological Sciences, University of Malakand, Chakdara, Pakistan
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Fehlmann T, Sahay S, Keller A, Backes C. A review of databases predicting the effects of SNPs in miRNA genes or miRNA-binding sites. Brief Bioinform 2020; 20:1011-1020. [PMID: 29186316 DOI: 10.1093/bib/bbx155] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 10/23/2017] [Indexed: 12/16/2022] Open
Abstract
Modern precision medicine comprises the knowledge and understanding of individual differences in the genomic sequence of patients to provide tailor-made treatments. Regularly, such variants are considered in coding regions only, and their effects are predicted based on their impact on the amino acid sequence of expressed proteins. However, assessing the effects of variants in noncoding elements, in particular microRNAs (miRNAs) and their binding sites, is important as well, as a single miRNA can influence the expression patterns of many genes at the same time. To analyze the effects of variants in miRNAs and their target sites, several databases storing variant impact predictions have been published. In this review, we will compare the core functionalities and features of these databases and discuss the importance of up-to-date data resources in the context of web applications. Finally, we will outline some recommendations for future developments in the field.
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Affiliation(s)
- Tobias Fehlmann
- Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany
| | - Shashwat Sahay
- Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany
| | - Andreas Keller
- Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany
| | - Christina Backes
- Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany
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Omariba G, Xu F, Wang M, Li K, Zhou Y, Xiao J. Genome-Wide Analysis of MicroRNA-related Single Nucleotide Polymorphisms (SNPs) in Mouse Genome. Sci Rep 2020; 10:5789. [PMID: 32238847 PMCID: PMC7113310 DOI: 10.1038/s41598-020-62588-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 03/02/2020] [Indexed: 12/20/2022] Open
Abstract
MicroRNAs are widely referred to as gene expression regulators for different diseases. The integration between single nucleotide polymorphisms (SNPs) and miRNAs has been associated with both human and animal diseases. In order to gain new insights on the effects of SNPs on miRNA and their related sequences, we steadily characterized a whole mouse genome miRNA related SNPs, analyzed their effects on the miRNA structural stability and target alteration. In this study, we collected 73643859 SNPs across the mouse genome, analyzed 1187 pre-miRNAs and 2027 mature miRNAs. Upon mapping the SNPs, 1700 of them were identified in 702 pre-miRNAs and 609 SNPs in mature miRNAs. We also discovered that SNP densities of the pre-miRNA and mature miRNAs are lower than the adjacent flanking regions. Also the flanking regions far away from miRNAs appeared to have higher SNP density. In addition, we also found that transitions were more frequent than transversions in miRNAs. Notably, 841 SNPs could change their corresponding miRNA's secondary structure from stable to unstable. We also performed target gain and loss analysis of 163 miRNAs and our results showed that few miRNAs remained unchanged and many miRNAs from wild mice gained target site. These results outline the first case of SNP variations in the mouse whole genome scale. Those miRNAs with changes in structure or target could be of interest for further studies.
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Affiliation(s)
- Gideon Omariba
- College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai, 201620, China
| | - Fuyi Xu
- College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai, 201620, China
- Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38163, United States
| | - Maochun Wang
- College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai, 201620, China
| | - Kai Li
- College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai, 201620, China
| | - Yuxun Zhou
- College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai, 201620, China
| | - Junhua Xiao
- College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai, 201620, China.
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Brincas HM, Augusto DG, Mathias C, Cavalli IJ, Lima RSD, Kuroda F, Urban CDA, Gradia DF, de Oliveira J, de Almeida RC, Ribeiro EMDSF. A genetic variant in microRNA-146a is associated with sporadic breast cancer in a Southern Brazilian Population. Genet Mol Biol 2020; 42:e20190278. [PMID: 32142098 PMCID: PMC7198002 DOI: 10.1590/1678-4685-gmb-2019-0278] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 11/21/2019] [Indexed: 01/20/2023] Open
Abstract
MicroRNAs (miRNAs) play an essential role in gene expression and affect the
development of tumours, including breast cancer (BC). Polymorphisms in miRNA
genes can affect the interaction of miRNAs with their target messenger RNA by
interfering, creating or disrupting target sites. The single nucleotide
polymorphism (SNP) rs2910164, located in the seed region of
miR146a, was shown to be associated with BC among different populations. In the
present study, we investigated whether rs2910164 is associated
with BC in 326 patients and 411 controls from a Brazilian population of
predominantly European ancestry. The presence of the allele
rs2910164*C was associated with an increased risk of BC
(OR=1.4, 95% CI=1.03-1.85, p = 0.03). We also analysed publicly
available RNA-seq data to evaluate if miR146a is differentially expressed in
different subtypes of BC. Genotyping was performed by polymerase chain reaction
with sequence-specific primers (PCR-SSP). By leveraging public data from TCGA
database, we analysed 461 patients and found that miR146a is significantly more
expressed in BC than in non-tumor tissue (1.47 fold, p = 0.02)
and is expressed to a greater degree in aggressive BC subtypes.
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Affiliation(s)
| | - Danillo G Augusto
- Hospital Nossa Senhora das Graças, Centro de Doenças da Mama, Curitiba, Paraná, Brazil
| | - Carolina Mathias
- Universidade Federal do Paraná, Departamento de Genética, Curitiba, Paraná, Brazil
| | - Iglenir João Cavalli
- Universidade Federal do Paraná, Departamento de Genética, Curitiba, Paraná, Brazil
| | | | - Flávia Kuroda
- Hospital Nossa Senhora das Graças, Centro de Doenças da Mama, Curitiba, Paraná, Brazil
| | | | - Daniela Fiori Gradia
- Universidade Federal do Paraná, Departamento de Genética, Curitiba, Paraná, Brazil
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Ibrahim RR, Amer RA, Abozeid AA, Elsharaby RM, Shafik NM. Micro RNA 146a gene variant / TNF-α / IL-6 / IL-1 β; A cross-link axis inbetween oxidative stress, endothelial dysfunction and neuro-inflammation in acute ischemic stroke and chronic schizophrenic patients. Arch Biochem Biophys 2020; 679:108193. [DOI: 10.1016/j.abb.2019.108193] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 11/09/2019] [Accepted: 11/12/2019] [Indexed: 12/18/2022]
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Weidhaas JB. Identifying MicroRNA Pathway Variants as Biomarkers of Patient Selection for Immune Therapy. Methods Mol Biol 2020; 2055:203-212. [PMID: 31502153 DOI: 10.1007/978-1-4939-9773-2_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
In this chapter we discuss the discovery and validation of microRNA (miRNA) associated germline biomarkers, as well as their application on a cohort of patients treated with immune therapy to predict response and toxicity. MiRNAs are the first class of noncoding RNAs discovered, and these pathways have been shown to be important regulators of the systemic stress response, including that to cancer therapy. We detail the original discovery efforts identifying germline biomarkers that disrupt miRNA circuitry, and then the selection, application, and validation of these biomarkers and their potential to predict important outcomes to checkpoint therapy.
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Affiliation(s)
- Joanne B Weidhaas
- Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA.
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Buranjiang G, Kuerban R, Abuduwanke A, Li X, Kuerban G. MicroRNA-331-3p inhibits proliferation and metastasis of ovarian cancer by targeting RCC2. Arch Med Sci 2019; 15:1520-1529. [PMID: 31749881 PMCID: PMC6855167 DOI: 10.5114/aoms.2018.77858] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 08/04/2018] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION Epithelial ovarian carcinoma (EOC) is one of the most lethal gynecologic malignancies, with a poor 5-year survival rate. Numerous studies have shown that microRNAs participate in the malignant behavior of ovarian cancer cells by directly targeting multiple oncogenes or tumor suppressor genes. MATERIAL AND METHODS Reverse transcription-PCR was used to determine the level of miR-331-3p in EOC. Cells proliferation was measured with the Cell Counting Kit-8. Cell mobility were measured by wound-healing assay. Cell migration and invasion were measured by transwell assay. Luciferase assays were used to demonstrate that RCC2 was a directed target of miR-331-3p in EOC. Western blots were used to measure the protein expression. RESULTS We found that the expression of microRNA-331-3p (miR-331-3p) in ovarian cancer cell lines is reduced (p < 0.01), and an increase of expression of miR-331-3p in ovarian cancer cells significantly inhibits cell proliferation (p < 0.001). Transwell and wound-healing assays showed that miR-331-3p inhibits the cell motility of ovarian cancer cells (p < 0.001). Regulator of chromosome condensation 2 (RCC2) was predicted to be a novel target for miR-331-3p. Our luciferase activity assay confirmed that RCC2 is directly targeted by miR-331-3p. RCC2 was negatively regulated by miR-331-3p (p < 0.001), and overexpression of RCC2 could restore the malignant behaviors of ovarian cancer cells, which was suppressed by miR-331-3p. CONCLUSIONS These data indicate that miR-331-3p can inhibit proliferation, migration, and invasion of ovarian cancer cells via directly targeting RCC2. Our study provides potential therapeutic targets for the treatment of ovarian cancer.
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Affiliation(s)
- Gulimire Buranjiang
- Department of Gynecologic Oncology Radiation Therapy (Ward II), Xinjiang Medical University Third Clinical Medical College (Affiliated Tumor Hospital), Urumqi, Xinjiang, China
| | - Reziya Kuerban
- Department of Gynecological Special Disease Clinic, Xinjiang Medical University Third Clinical Medical College (Affiliated Tumor Hospital), Urumqi, Xinjiang, China
| | - Ailikemu Abuduwanke
- Department of Pediatric Ward, Xinjiang Uygur Autonomous Region People’s Hospital, Urumqi, Xinjiang, China
| | - Xiaowen Li
- Department of Gynecologic Oncology Radiation Therapy (Ward II), Xinjiang Medical University Third Clinical Medical College (Affiliated Tumor Hospital), Urumqi, Xinjiang, China
| | - Gulina Kuerban
- Department of Gynecologic Oncology Radiation Therapy (Ward II), Xinjiang Medical University Third Clinical Medical College (Affiliated Tumor Hospital), Urumqi, Xinjiang, China
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Abstract
BACKGROUND Previous studies have demonstrated that single-nucleotide polymorphisms (SNPs) in miRNAs are related to the susceptibility to brain tumors, but the conclusions remain controversial. This study was to perform a meta-analysis to re-assess the associations between miRNA SNPs and brain tumor risk. METHODS Relevant studies were identified in the databases of PubMed and the Cochrane Library databases. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the relationships between SNPs and the risk of brain tumors under various genetic models by the STATA software. RESULTS Five studies, containing 2275 cases, and 2323 controls, were included, 4 of which evaluated miR-196a2 (rs11614913), 3 for miR-146a (rs2910164) and 2 for miR-499 (rs3746444) and miR-149 (rs2292832), respectively. The meta-analysis indicated that the GG genotype carriers of miR-146a were more susceptible to brain tumors compared with GC genotype carriers (OR = 1.19, 95%CI = 1.01-1.41, P = .036). No significant associations were observed between the SNPs of other miRNAs and the risk of brain tumors. Furthermore, all miRNA polymorphisms did not show significant associations with the risk of glioma subgroup in any genetic models, while meta-analysis of non-glioma subgroup could not be performed due to low statistical power and analysis of only 1 study. CONCLUSION Our study suggests that miR-146a polymorphism may modify the risk for brain tumors, but which type (glioma or benign non-glioma tumors) should be verified with large sample size.
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Affiliation(s)
| | - Yuntao Zhu
- Department of Clinical Laboratory, People's Hospital of Jinxiang, Jining 272200, Shandong Province, China
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Dostal Z, Modriansky M. The effect of quercetin on microRNA expression: A critical review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2019; 163:95-106. [PMID: 31263290 DOI: 10.5507/bp.2019.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 06/11/2019] [Indexed: 02/06/2023] Open
Abstract
Quercetin, a flavonoid with multiple proven health benefits to both man and animals, displays a plethora of biological activities, collectively referred to as pleiotropic. The most studied of these are antioxidant and anti-inflammatory but modulation of signalling pathways is important as well. One of the lesser-known and recently discovered roles of quercetin, is modulation of microRNA (miRNA) expression. miRNAs are important posttranscriptional modulators that play a critical role in health and disease and many of these non-coding oligonucleotides are recognized as oncogenic or tumor suppressor miRNAs. This review is an evaluation of the recent relevant literature on the subject, with focus on the ability of quercetin to modulate miRNA expression. It includes a summary of recent knowledge on miRNAs deregulated by quercetin, an overview of quercetin pharmacokinetics and miRNA biogenesis, for the interested reader.
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Affiliation(s)
- Zdenek Dostal
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.,Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic Corresponding author: Martin Modriansky, e-mail
| | - Martin Modriansky
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.,Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic Corresponding author: Martin Modriansky, e-mail
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Rajalingam D, Jacobsen DP, Nielsen MB, Einarsen SV, Gjerstad J. Exposure to Workplace Bullying, Distress, and Insomnia: The Moderating Role of the miR-146a Genotype. Front Psychol 2019; 10:1204. [PMID: 31178808 PMCID: PMC6542980 DOI: 10.3389/fpsyg.2019.01204] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 05/07/2019] [Indexed: 12/29/2022] Open
Abstract
Several lines of evidence show that systematic exposure to negative social acts at the workplace i.e., workplace bullying, results in symptoms of depression and anxiety among those targeted. However, little is known about the association between bullying, inflammatory genes and sleep problems. In the present study, we examined the indirect association between exposure to negative social acts and sleep through distress, as moderated by the miR-146a genotype. The study was based on a nationally representative survey of 1179 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to workplace bullying was measured with the 9-item version of Negative Acts Questionnaire - Revised (NAQ-R) inventory. Seventeen items from Hopkins Symptom Checklist (HSCL-25) was used to measure distress. Insomnia was assessed with three items reflecting problems with sleep onset, maintenance of sleep and early morning awakening. Genotyping with regard to miR-146a rs2910164, previously linked to inflammatory processes, was carried out using Taqman assay. The data revealed that individuals systematically exposed to negative social acts at the workplace reported higher levels of sleep problems than non-exposed individuals. Moreover, the relationship between distress induced by exposure to negative social acts and insomnia was significantly stronger for individuals with the miR-146a GG genotype. Thus, the miR-146a genotype moderated the association between distress and insomnia among individuals exposed to negative social acts. The present report support the hypothesis that inflammation could play a role in stress-induced insomnia among individuals exposed to workplace bullying.
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Affiliation(s)
| | | | - Morten Birkeland Nielsen
- Department of Psychosocial Science, University of Bergen, Bergen, Norway
- National Institute of Occupational Health, Oslo, Norway
| | | | - Johannes Gjerstad
- Department of Psychosocial Science, University of Bergen, Bergen, Norway
- National Institute of Occupational Health, Oslo, Norway
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Heidari Z, Mohammadpour-Gharehbagh A, Eskandari M, Harati-Sadegh M, Salimi S. Genetic polymorphisms of miRNA let7a-2 and pri-mir-34b/c are associated with an increased risk of papillary thyroid carcinoma and clinical/pathological features. J Cell Biochem 2019; 120:8640-8647. [PMID: 30552691 DOI: 10.1002/jcb.28152] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Accepted: 11/05/2018] [Indexed: 01/24/2023]
Abstract
microRNAs (miRNAs) as a group of short noncoding RNAs are crucial molecules in transcriptional and translational regulation of oncogenes and tumor suppressor genes. Evidence showed there was an association between the miRNA polymorphisms and various cancers, including papillary thyroid carcinoma (PTC). The present study aims to evaluate the possible effects of let7a-2 rs1143770 and pri-mir-34b/c rs4938723 polymorphisms on PTC susceptibility. A total of 120 patients with PTC and 130 age, sex, and race matched controls were enrolled in the case-control study. The polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping of let7a-2 rs1143770 and pri-mir-34b/c rs4938723 polymorphisms. The let7a-2 rs1143770 CT and TT genotypes were associated with a 1.9-fold and 2.2-fold higher risk of PTC, respectively (P = 0.027 and P = 0.041). Moreover, the let7a-2 rs1143770 polymorphism was associated with increased PTC risk in both dominant (2-fold, P = 0.015) and the allelic model (1.5-fold, P = 0.03). The frequency of pri-mir-34b/c rs4938723TC genotype was significantly higher in patients with PTC and associated with a two-fold higher risk of PTC (P = 0.013). In addition, this polymorphism was associated with a 1.8-fold increased risk of PTC in dominant model (P = 0.021). The let7a-2 rs1143770CT genotype was associated with a 3.5-fold increased risk of N1 stage in PTC patients (P = 0.04), however, pri-mir-34b/c rs4938723TC genotype was associated with a 3.4-fold and 5.1-fold increased risk of III-IV stage and vascular invasion in PTC group, respectively (P = 0.04 and P = 0.04). In conclusion, the present study shows that let7a-2 rs1143770 and pri-mir-34b/c rs4938723 polymorphisms could be susceptible factors for PTC and some clinical features.
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Affiliation(s)
- Zahra Heidari
- Department of Endocrinology, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | - Moein Eskandari
- Department of Laboratory Sciences, School of Paramedical Sciences, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mahdiyeh Harati-Sadegh
- Department of Genetics, Fars Science and Research Branch, Islamic Azad University, Marvdasht, Iran.,Department of Genetics, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
| | - Saeedeh Salimi
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.,Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
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Thakur N, Singhal P, Mehrotra R, Bharadwaj M. Impacts of single nucleotide polymorphisms in three microRNAs (miR-146a, miR-196a2 and miR-499) on the susceptibility to cervical cancer among Indian women. Biosci Rep 2019; 39:BSR20180723. [PMID: 30872409 PMCID: PMC6465206 DOI: 10.1042/bsr20180723] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 01/08/2019] [Accepted: 01/14/2019] [Indexed: 12/26/2022] Open
Abstract
Background: Cervical cancer is the second major female cancer in India and constitutes one-fourth of the world's burden. Human Papilloma Virus (HPV) infection is an essential but insufficient cause for cervical cancer. Genetic variants in microRNAs (miRNAs/miRs) play an important role in the susceptibility of various types of cancers.Objective: To evaluate the association of Single Nucleotide Polymorphisms (SNPs) in miR-146a (rs2910164), miR-196a2 (rs11614913), and miR-499 (rs3746444), with cervical cancer susceptibility in Indian population.Methods: Three hundred samples were genotyped by Polymerase chain reaction (PCR)-Restriction fragment length polymorphism (RFLP). Both patients and controls were also screened for the presence of HPV DNA.Results: In this case-control study, 125 (83.3%) cervical cancer cases were found to be infected with HPV DNA. The frequency of miR-146a C allele was higher in controls than in cases [odds ratio (OR) (95% confidence interval (CI)) = 0.81 (0.57-1.14), P-value = 0.258]. miR-196a2 T allele was found to be associated with the decreased risk of cervical cancer [OR (95% CI) = 0.36 (0.26-0.50), P-value<0.0001]. Approximately 1.22-fold increased risk has been observed in individuals carrying miR-499 TT genotypes [OR (95% CI) = 1.22 (0.63-2.36), P-value = 0.617]. Interaction studies for miR-196a2/miR-499 loci showed that women carrying TT/CC and TT/CT genotypes were less likely to develop cervical cancer than CC/CC combination [P<0.05]. Likewise, miR-146a/miR-196a2 genotypic combinations (CC/TT, CG/TT, GG/TT) followed the similar trend [P<0.05], exhibited the protective effect against cervical cancer with reference to CC/CC group. Combined genotypes of miR-146a/miR-499 [CC/CT, CG/CC, CG/CT, CG/TT, GG/CC, GG/CT, GG/TT] demonstrated a non-significant trend toward higher cervical cancer risk [OR > 1.00, P>0.05].Conclusion: Polymorphisms in miR-146a, miR-196a2, and miR-499 individually or collectively have the prospective to emerge as biomarkers for cervical cancer.
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Affiliation(s)
- Nisha Thakur
- Division of Molecular Genetics and Biochemistry, National Institute of Cancer Prevention and Research (ICMR), Noida, Uttar Pradesh, India
| | - Pallavi Singhal
- Division of Molecular Genetics and Biochemistry, National Institute of Cancer Prevention and Research (ICMR), Noida, Uttar Pradesh, India
| | - Ravi Mehrotra
- Division of Preventive Oncology, National Institute of Cancer Prevention and Research (Formerly Institute of Cytology and Preventive Oncology (ICPO) (ICMR), I-7, Sector-39, Noida, Gautam Buddha Nagar, Uttar Pradesh 201301, India
| | - Mausumi Bharadwaj
- Division of Molecular Genetics and Biochemistry, National Institute of Cancer Prevention and Research (ICMR), Noida, Uttar Pradesh, India
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Ahmad M, Ahmad S, Rahman B, Haq TU, Jalil F, Shah AA. Association of MIR146A rs2910164 variation with a predisposition to sporadic breast cancer in a Pakistani cohort. Ann Hum Genet 2019; 83:325-330. [PMID: 30963551 DOI: 10.1111/ahg.12316] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 02/26/2019] [Accepted: 03/19/2019] [Indexed: 12/24/2022]
Abstract
Single-nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 GC polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated and the association between genotypes and the risk of BC was calculated by odds ratio (OR) and confidence interval (95%). A significant difference in genotypic frequencies (χ2 = 63.10; P = <0.0001) and allelic frequencies (OR = 0.3955 (0.3132-0.4993); P = < 0.0001) was observed between cases and controls. Furthermore, we also found that miR-146 rs2910164 CC homozygote increased the risk of BC in the dominant (OR = 0.2397 (0.1629-0.3526); P = 0.0001; GG vs. GC + CC) and recessive (OR = 2.803 (1.865-4.213); P = <0.0001; CC vs. GC + GG) inheritance models. In summary, miR-146a rs2910164 GC is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G > C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm of these findings.
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Affiliation(s)
- Mushtaq Ahmad
- Department of Biotechnology, University of Malakand, Chakdara, Pakistan
| | - Sadia Ahmad
- Department of Biotechnology, University of Malakand, Chakdara, Pakistan
| | - Bashir Rahman
- Department of Biotechnology, University of Malakand, Chakdara, Pakistan
| | - Taqweem Ul Haq
- Department of Biotechnology, University of Malakand, Chakdara, Pakistan
| | - Fazal Jalil
- Department of Biotechnology, Abdul Wali Khan University Mardan (AWKUM), Mardan, Pakistan
| | - Aftab Ali Shah
- Department of Biotechnology, University of Malakand, Chakdara, Pakistan
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Lukács J, Soltész B, Penyige A, Nagy B, Póka R. Identification of miR-146a and miR-196a-2 single nucleotide polymorphisms at patients with high-grade serous ovarian cancer. J Biotechnol 2019; 297:54-57. [PMID: 30904593 DOI: 10.1016/j.jbiotec.2019.03.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 03/19/2019] [Accepted: 03/19/2019] [Indexed: 12/17/2022]
Abstract
MicroRNAs play an essential role in the regulation of gene expression and tumor development. Single nucleotide polymorphism (SNP) can be observed in miRNAs and could influence gene expression. We aimed to identify miR-146a rs2910164 and miR-196a-2 rs11614913 polymorphisms in ovarian cancer patients and controls. 75 patients and 75 controls were involved. DNA was isolated from blood samples. MiR-146a rs2910164 and miR-196a-2 rs11614913 were determined by LightSnip kit. We used melting curve analysis for allele classification. Network analysis was made to find common target genes. We detected 72.67% G allele frequency of miR-146a rs2910164 in controls and 82.00% in patients group (p = 0,053). GG, GC and CC genotypes occurred with 53.33%, 38.67% and 8.00% among controls, with 65.33%, 33.33% and 1.33% among patients, (p = 0.0917). Allele C of miR-196a-2 rs11614913 occurred in 59.33% of controls and in 67.33% of patients (p = 0.15). CC, CT and TT genotypes occurred with 37.33%, 44.00%, and 18.67% frequency in controls, with 46.67%; 41.33% and 12.00% in patients (p = 0.3815). Network analysis found ATG9A, LBR, MBD4 and RUFY2 genes to be targets for both miRNAs. SNPs of miR-146a and miR-196a-2 showed no significant differences between patients and controls. More investigations are required to clarify the exact role of these SNPs in ovarian cancer.
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Affiliation(s)
- János Lukács
- Department of Obstetrics and Gynecology, University of Debrecen, Debrecen Hungary
| | - Beáta Soltész
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Debrecen Hungary
| | - András Penyige
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Debrecen Hungary
| | - Bálint Nagy
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, Debrecen Hungary
| | - Róbert Póka
- Department of Obstetrics and Gynecology, University of Debrecen, Debrecen Hungary.
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McAnena P, Lowery A, Kerin MJ. Role of micro-RNAs in breast cancer surgery. Br J Surg 2018; 105:e19-e30. [PMID: 29341144 DOI: 10.1002/bjs.10790] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 11/17/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND The management of breast cancer has changed dramatically in the molecular era. Micro-RNAs can contribute to multiple facets of cancer surgery. METHODS This narrative review, based on years of research on the role of micro-RNAs, focused on the potential of these small, robust RNAs to influence all aspects of breast cancer surgery. RESULTS Micro-RNAs have a potential role as biomarkers in the diagnosis, prognosis and evaluation of response to therapy in breast cancer. They may also contribute to future therapeutic strategies. CONCLUSION The molecular era has changed understanding of cancer. Micro-RNAs have the potential for use in personalized cancer strategies.
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Affiliation(s)
- P McAnena
- Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland, Galway, Ireland
| | - A Lowery
- Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland, Galway, Ireland
| | - M J Kerin
- Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland, Galway, Ireland
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Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis. Immunol Lett 2018; 204:1-8. [DOI: 10.1016/j.imlet.2018.10.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 09/24/2018] [Accepted: 10/07/2018] [Indexed: 12/14/2022]
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Thapar R. Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs. Molecules 2018; 23:molecules23112789. [PMID: 30373256 PMCID: PMC6278438 DOI: 10.3390/molecules23112789] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 10/25/2018] [Accepted: 10/26/2018] [Indexed: 01/12/2023] Open
Abstract
DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs. Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair.
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Affiliation(s)
- Roopa Thapar
- Department of Molecular and Cellular Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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