ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental Approach
Background and purpose: after heart diseases and accidents, cancer is considered the third cause of death in Iran (1), and is a major health problem not only in Iran but also in many developed and developing countries. (2). Breast cancer is a disease in which breast cells grow out of control. This d...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Mazandaran University of Medical Sciences
2024-02-01
|
| Series: | Journal of Mazandaran University of Medical Sciences |
| Subjects: | |
| Online Access: | http://jmums.mazums.ac.ir/article-1-20350-en.pdf |
| _version_ | 1797260161172111360 |
|---|---|
| author | Pardis Mirzaeyan Mohammad Shokrzadeh Ali Salehzadeh Farzam Ajamian |
| author_facet | Pardis Mirzaeyan Mohammad Shokrzadeh Ali Salehzadeh Farzam Ajamian |
| author_sort | Pardis Mirzaeyan |
| collection | DOAJ |
| description | Background and purpose: after heart diseases and accidents, cancer is considered the third cause of death in Iran (1), and is a major health problem not only in Iran but also in many developed and developing countries. (2). Breast cancer is a disease in which breast cells grow out of control. This disease has different types based on the type of breast cells that become cancerous. Breast cancer accounts for about one-third of all types of cancer in the female population and is the main cause of cancer-related deaths in women worldwide (3). Estrogen receptor-α is one of the isoforms of estrogen receptor encoded by the ESR1 gene. ESR-α is a nuclear receptor that acts as a ligand-dependent transcription factor (4). After binding of estrogen, ESR-α binds to the estrogen response regions in the promoter of the target genes and causes changes in the expression of the target genes (5). The present study investigates the expression level of the estrogen receptor gene (ESR1) and long non-coding RNAs (lncRNAs) related to It investigates the allele frequency and genotype of single nucleotide polymorphism (SNP) rs2234693 in ESR1 gene in patients with breast cancer.
Materials and methods: In this case-control study, the expression of ESR1 and related coding and non-coding RNAs were investigated by microarray (17 control samples and 104 patient samples), TCGA RNAseq (on 113 normal samples, 1102 primary tumors and seven Metastatic tumor samples) and data analysis was done by R Studio and limma, and ENCORI and GEPIA2 databases. Evaluation of microRNA interaction was done by miRWalk and lncRNA interaction finding was done by lncBase 3. Protein-protein interaction was analyzed by STRING and survival and correlation analysis by GEPIA2 and ENCORI. Pathway enrichment and gene ontology (GO) analyses were performed by KEGG and Enrichr and SNP analysis was performed by RFLP test.
Results: ESR1 gene expression was increased in breast cancer and miR-15a-3p gene had a significant interaction with ESR1 and lncRNA OIP5-AS1. OIP5-AS1 and ESR1 had significant positive expression in patient samples. The frequency of TC, TT, and CC genotypes in healthy people was 65%, 15%, and 20%, respectively, and in the patient group it was 38.5%, 38.5% and 23%. There was a significant difference in the prevalence of ESR1 gene genotypes between patients and controls.
Conclusion: ESR1 polymorphism may be associated with an increased risk of breast cancer and rs2234693 T>C SNP can be considered a strong marker for breast cancer screening. OIP5-AS1 may regulate breast cancer progression by altering ESR1 expression regulation. |
| first_indexed | 2024-04-24T23:20:55Z |
| format | Article |
| id | doaj.art-bca6d4a5f75f4b41a7c98a4109b4cfab |
| institution | Directory Open Access Journal |
| issn | 1735-9260 1735-9279 |
| language | English |
| last_indexed | 2024-04-24T23:20:55Z |
| publishDate | 2024-02-01 |
| publisher | Mazandaran University of Medical Sciences |
| record_format | Article |
| series | Journal of Mazandaran University of Medical Sciences |
| spelling | doaj.art-bca6d4a5f75f4b41a7c98a4109b4cfab2024-03-16T11:16:05ZengMazandaran University of Medical SciencesJournal of Mazandaran University of Medical Sciences1735-92601735-92792024-02-01332305069ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental ApproachPardis Mirzaeyan0Mohammad Shokrzadeh1Ali Salehzadeh2Farzam Ajamian3 PhD Student in Cellular and Molecular Biology, Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran Professor, Pharmaceutical Research Center, Department of Toxicology and Pharmacology, Mazandaran University of Medical Sciences, Sari, Iran and Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran Associate Professor, Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran Assistant Professor, Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran Background and purpose: after heart diseases and accidents, cancer is considered the third cause of death in Iran (1), and is a major health problem not only in Iran but also in many developed and developing countries. (2). Breast cancer is a disease in which breast cells grow out of control. This disease has different types based on the type of breast cells that become cancerous. Breast cancer accounts for about one-third of all types of cancer in the female population and is the main cause of cancer-related deaths in women worldwide (3). Estrogen receptor-α is one of the isoforms of estrogen receptor encoded by the ESR1 gene. ESR-α is a nuclear receptor that acts as a ligand-dependent transcription factor (4). After binding of estrogen, ESR-α binds to the estrogen response regions in the promoter of the target genes and causes changes in the expression of the target genes (5). The present study investigates the expression level of the estrogen receptor gene (ESR1) and long non-coding RNAs (lncRNAs) related to It investigates the allele frequency and genotype of single nucleotide polymorphism (SNP) rs2234693 in ESR1 gene in patients with breast cancer. Materials and methods: In this case-control study, the expression of ESR1 and related coding and non-coding RNAs were investigated by microarray (17 control samples and 104 patient samples), TCGA RNAseq (on 113 normal samples, 1102 primary tumors and seven Metastatic tumor samples) and data analysis was done by R Studio and limma, and ENCORI and GEPIA2 databases. Evaluation of microRNA interaction was done by miRWalk and lncRNA interaction finding was done by lncBase 3. Protein-protein interaction was analyzed by STRING and survival and correlation analysis by GEPIA2 and ENCORI. Pathway enrichment and gene ontology (GO) analyses were performed by KEGG and Enrichr and SNP analysis was performed by RFLP test. Results: ESR1 gene expression was increased in breast cancer and miR-15a-3p gene had a significant interaction with ESR1 and lncRNA OIP5-AS1. OIP5-AS1 and ESR1 had significant positive expression in patient samples. The frequency of TC, TT, and CC genotypes in healthy people was 65%, 15%, and 20%, respectively, and in the patient group it was 38.5%, 38.5% and 23%. There was a significant difference in the prevalence of ESR1 gene genotypes between patients and controls. Conclusion: ESR1 polymorphism may be associated with an increased risk of breast cancer and rs2234693 T>C SNP can be considered a strong marker for breast cancer screening. OIP5-AS1 may regulate breast cancer progression by altering ESR1 expression regulation.http://jmums.mazums.ac.ir/article-1-20350-en.pdfsingle nucleotide polymorphismbreast canceresr1 generflp-pcrrs2234693mirnacerna network |
| spellingShingle | Pardis Mirzaeyan Mohammad Shokrzadeh Ali Salehzadeh Farzam Ajamian ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental Approach Journal of Mazandaran University of Medical Sciences single nucleotide polymorphism breast cancer esr1 gene rflp-pcr rs2234693 mirna cerna network |
| title | ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental Approach |
| title_full | ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental Approach |
| title_fullStr | ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental Approach |
| title_full_unstemmed | ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental Approach |
| title_short | ESR1 Could be a Novel Target of miR-15a-3p and lncRNA OIP5-AS1 in the Breast Cancer Patients, Regulating by rs2234693 Polymorphism: Integrated Bioinformatics and Experimental Approach |
| title_sort | esr1 could be a novel target of mir 15a 3p and lncrna oip5 as1 in the breast cancer patients regulating by rs2234693 polymorphism integrated bioinformatics and experimental approach |
| topic | single nucleotide polymorphism breast cancer esr1 gene rflp-pcr rs2234693 mirna cerna network |
| url | http://jmums.mazums.ac.ir/article-1-20350-en.pdf |
| work_keys_str_mv | AT pardismirzaeyan esr1couldbeanoveltargetofmir15a3pandlncrnaoip5as1inthebreastcancerpatientsregulatingbyrs2234693polymorphismintegratedbioinformaticsandexperimentalapproach AT mohammadshokrzadeh esr1couldbeanoveltargetofmir15a3pandlncrnaoip5as1inthebreastcancerpatientsregulatingbyrs2234693polymorphismintegratedbioinformaticsandexperimentalapproach AT alisalehzadeh esr1couldbeanoveltargetofmir15a3pandlncrnaoip5as1inthebreastcancerpatientsregulatingbyrs2234693polymorphismintegratedbioinformaticsandexperimentalapproach AT farzamajamian esr1couldbeanoveltargetofmir15a3pandlncrnaoip5as1inthebreastcancerpatientsregulatingbyrs2234693polymorphismintegratedbioinformaticsandexperimentalapproach |