Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients
BackgroundNon−small-cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are novel markers and targets in cancer therapy and can act as both tumor suppressors and oncogenes and affect immune function. The aim of this study was to investigate the expression of miR146a and miR...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.715677/full |
| _version_ | 1818729716578779136 |
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| author | Neda K. Dezfuli Neda K. Dezfuli Shamila D. Alipoor Neda Dalil Roofchayee Neda Dalil Roofchayee Sharareh Seyfi Babak Salimi Ian M. Adcock Esmaeil Mortaz Esmaeil Mortaz |
| author_facet | Neda K. Dezfuli Neda K. Dezfuli Shamila D. Alipoor Neda Dalil Roofchayee Neda Dalil Roofchayee Sharareh Seyfi Babak Salimi Ian M. Adcock Esmaeil Mortaz Esmaeil Mortaz |
| author_sort | Neda K. Dezfuli |
| collection | DOAJ |
| description | BackgroundNon−small-cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are novel markers and targets in cancer therapy and can act as both tumor suppressors and oncogenes and affect immune function. The aim of this study was to investigate the expression of miR146a and miR155 in linked to blood immune cell phenotypes and serum cytokines in NSCLC patients.MethodsThirty-three NSCLC patients and 30 healthy subjects were enrolled in this study. The allele frequencies of potential DNA polymorphisms were studied using polymerase chain reaction (PCR)–restriction fragment length polymorphism (PCR-RFLP) analysis in peripheral blood samples. Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of miR-146a and miR-155 in peripheral blood mononuclear cells (PBMCs). Serum cytokine (IL-1β, IL-6, TNF-α, TGF-β, IL-4, IFN-γ) levels were determined by ELISA. The frequency of circulating CD3+CTLA-4+ and CD4+CD25+FOXP3+ (T regulatory cells/Treg) expression was measured by flow cytometry.ResultsmiR-146a was significantly downregulated in PBMC of NSCLC patients (P ≤ 0.001). Moreover, IL-6 and TGF-β levels were elevated in NSCLC patients (P ≤ 0.001, P ≤ 0.018, respectively). CD3+ CTLA-4+ and Treg cells frequencies were higher in patients than in control subjects (P ≤ 0.0001, P ≤ 0.0001, respectively). There was a positive correlation between miR-155 and IL-1β levels (r=0.567, p ≤ 0.001) and a negative correlation between miR-146a and TGF-β levels (r=-0.376, P ≤ 0.031) in NSCLC patients. No significant differences were found in the relative expression of miR-146a and miR-155, cytokine levels or immune cell numbers according to miR-146a and miR-155 (GG/GC/CC, TT/AT/AA) genotypes. However, there was a positive correlation between miR-146a and IL-1β levels (r=0.74, P ≤ 0.009) in GG subjects and a positive correlation between miR-146a expression and CD3+CTLA4+ cell frequency (r=0.79, P ≤ 0.01) in CC genotyped subjects. Conversely, a negative correlation between miR-146a expression and Treg cell frequency (r=−0.87, P ≤ 0.05) was observed with the GG genotype. A positive correlation between miR-155 and IL-1β expression (r=0.58, p ≤ 0.009) in the TT genotype and between miR-155 expression and CD3+CTLA-4 cell frequency (r=0.75, P ≤ 0.01) was observed in the AT genotype.ConclusionsThe current data suggest that the miR-146a expression in PBMC and serum TGF-β and IL-1β levels may act as blood markers in NSCLC patients. Further study is needed to elucidate the link between immune cells and serum miR146 at early disease stages. |
| first_indexed | 2024-12-17T22:50:19Z |
| format | Article |
| id | doaj.art-26efb93a1b9e4a3f9d1535d2d16809d3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T22:50:19Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-26efb93a1b9e4a3f9d1535d2d16809d32022-12-21T21:29:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-11-011110.3389/fonc.2021.715677715677Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer PatientsNeda K. Dezfuli0Neda K. Dezfuli1Shamila D. Alipoor2Neda Dalil Roofchayee3Neda Dalil Roofchayee4Sharareh Seyfi5Babak Salimi6Ian M. Adcock7Esmaeil Mortaz8Esmaeil Mortaz9Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Immunology and Laboratory Sciences, School of Allied Medical Sciences, Dezful University of Medical Sciences, Dezful, IranMolecular Medicine Department, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, IranClinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranChronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, IranChronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, IranAirways Disease Section, National Heart and Lung Institute, Imperial College London, London, United KingdomClinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranBackgroundNon−small-cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are novel markers and targets in cancer therapy and can act as both tumor suppressors and oncogenes and affect immune function. The aim of this study was to investigate the expression of miR146a and miR155 in linked to blood immune cell phenotypes and serum cytokines in NSCLC patients.MethodsThirty-three NSCLC patients and 30 healthy subjects were enrolled in this study. The allele frequencies of potential DNA polymorphisms were studied using polymerase chain reaction (PCR)–restriction fragment length polymorphism (PCR-RFLP) analysis in peripheral blood samples. Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of miR-146a and miR-155 in peripheral blood mononuclear cells (PBMCs). Serum cytokine (IL-1β, IL-6, TNF-α, TGF-β, IL-4, IFN-γ) levels were determined by ELISA. The frequency of circulating CD3+CTLA-4+ and CD4+CD25+FOXP3+ (T regulatory cells/Treg) expression was measured by flow cytometry.ResultsmiR-146a was significantly downregulated in PBMC of NSCLC patients (P ≤ 0.001). Moreover, IL-6 and TGF-β levels were elevated in NSCLC patients (P ≤ 0.001, P ≤ 0.018, respectively). CD3+ CTLA-4+ and Treg cells frequencies were higher in patients than in control subjects (P ≤ 0.0001, P ≤ 0.0001, respectively). There was a positive correlation between miR-155 and IL-1β levels (r=0.567, p ≤ 0.001) and a negative correlation between miR-146a and TGF-β levels (r=-0.376, P ≤ 0.031) in NSCLC patients. No significant differences were found in the relative expression of miR-146a and miR-155, cytokine levels or immune cell numbers according to miR-146a and miR-155 (GG/GC/CC, TT/AT/AA) genotypes. However, there was a positive correlation between miR-146a and IL-1β levels (r=0.74, P ≤ 0.009) in GG subjects and a positive correlation between miR-146a expression and CD3+CTLA4+ cell frequency (r=0.79, P ≤ 0.01) in CC genotyped subjects. Conversely, a negative correlation between miR-146a expression and Treg cell frequency (r=−0.87, P ≤ 0.05) was observed with the GG genotype. A positive correlation between miR-155 and IL-1β expression (r=0.58, p ≤ 0.009) in the TT genotype and between miR-155 expression and CD3+CTLA-4 cell frequency (r=0.75, P ≤ 0.01) was observed in the AT genotype.ConclusionsThe current data suggest that the miR-146a expression in PBMC and serum TGF-β and IL-1β levels may act as blood markers in NSCLC patients. Further study is needed to elucidate the link between immune cells and serum miR146 at early disease stages.https://www.frontiersin.org/articles/10.3389/fonc.2021.715677/fullcytokinesimmune systemNSCLCmiR-155miR-146a |
| spellingShingle | Neda K. Dezfuli Neda K. Dezfuli Shamila D. Alipoor Neda Dalil Roofchayee Neda Dalil Roofchayee Sharareh Seyfi Babak Salimi Ian M. Adcock Esmaeil Mortaz Esmaeil Mortaz Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients Frontiers in Oncology cytokines immune system NSCLC miR-155 miR-146a |
| title | Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients |
| title_full | Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients |
| title_fullStr | Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients |
| title_full_unstemmed | Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients |
| title_short | Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients |
| title_sort | evaluation expression of mir 146a and mir 155 in non small cell lung cancer patients |
| topic | cytokines immune system NSCLC miR-155 miR-146a |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.715677/full |
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