MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells
IntroductionThe role of miRNAs in regulating variable molecular functions has been sought by scientists for its promising utility in regulating the immune response and, hence, in treating various diseases. In hepatocellular carcinoma (HCC) specifically, a reduction in the number and efficiency of ci...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1523068/full |
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| author | Rowan Abdelbary Rowan Abdelbary Manon Ragheb Manon Ragheb Shereen A. El Sobky Nagwa El-Badri Nourhan Aboud Ahmed Tawheed Asmaa Gomaa Mona Zidan Ramy K. Aziz Abd Elrahman Abouzid Radwa Ayman Salah Mohamed El-Kassas Imam Waked Ahmed Moustafa Ahmed Moustafa Injie Omar Fawzy Nada El-Ekiaby Ahmed Ihab Abdelaziz |
| author_facet | Rowan Abdelbary Rowan Abdelbary Manon Ragheb Manon Ragheb Shereen A. El Sobky Nagwa El-Badri Nourhan Aboud Ahmed Tawheed Asmaa Gomaa Mona Zidan Ramy K. Aziz Abd Elrahman Abouzid Radwa Ayman Salah Mohamed El-Kassas Imam Waked Ahmed Moustafa Ahmed Moustafa Injie Omar Fawzy Nada El-Ekiaby Ahmed Ihab Abdelaziz |
| author_sort | Rowan Abdelbary |
| collection | DOAJ |
| description | IntroductionThe role of miRNAs in regulating variable molecular functions has been sought by scientists for its promising utility in regulating the immune response and, hence, in treating various diseases. In hepatocellular carcinoma (HCC) specifically, a reduction in the number and efficiency of circulating and intrahepatic natural killer (NK) cells has been reported. Our project aims to investigate the role of miR-216a-3p in the regulation of NK cell cytotoxicity, especially since it plays a tumor suppressor role in the context of HCC.MethodsTo achieve our aim, we isolated NK cells from the whole blood of 86 patients with HCC and 23 healthy controls. We assessed the expression profile of miR-216a-3p in NK cells of patients and controls. Furthermore, we induced the expression of miR-216a-3p in NK cells isolated from healthy controls, followed by measuring the release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), perforins (PRF) and granzyme B (GrB) using ELISA as well as NK cells cytolytic activity against Huh7 cells using lactate dehydrogenase (LDH) cytotoxicity assay. After that, we performed an in silico analysis to understand the mechanistic regulation imposed by miR-216a-3p on NK cells to study its impact on one of its potential downstream targets.ResultsOur results have indicated that miR-216a-3p has higher expression in NK cells of patients with HCC, and simulating this elevated expression pattern via forcing miR-216a-3p expression in normal NK cells has negatively impacted the release of TNF- α, IFN- γ, GrB, and PRF. Consequently, a decrease in cell cytolysis was observed. Our in silico analysis revealed that the predicted downstream targets of miR-216a-3p are enriched in the FOXO-signaling pathway. Among those targets is FOXO-1, which has been reported to play a role in NK cell maturation. Thus, we evaluated FOXO-1 expression upon mimicking miR-216a-3p in control NK cells that showed significant downregulation of FOXO-1 on both RNA and protein levels.ConclusionIn conclusion, we report miR-216-3p as a negative regulator of NK cell cytotoxicity. |
| format | Article |
| id | doaj-art-a52ce6ce3a644729b6c7a55874ee2409 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-a52ce6ce3a644729b6c7a55874ee24092025-01-21T08:37:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15230681523068MiR-216a-3p inhibits the cytotoxicity of primary natural killer cellsRowan Abdelbary0Rowan Abdelbary1Manon Ragheb2Manon Ragheb3Shereen A. El Sobky4Nagwa El-Badri5Nourhan Aboud6Ahmed Tawheed7Asmaa Gomaa8Mona Zidan9Ramy K. Aziz10Abd Elrahman Abouzid11Radwa Ayman Salah12Mohamed El-Kassas13Imam Waked14Ahmed Moustafa15Ahmed Moustafa16Injie Omar Fawzy17Nada El-Ekiaby18Ahmed Ihab Abdelaziz19Biotechnology Graduate Program, American University in New Cairo, Cairo, EgyptSchool of Medicine, Newgiza University (NGU), Giza, EgyptBiotechnology Graduate Program, American University in New Cairo, Cairo, EgyptSchool of Medicine, Newgiza University (NGU), Giza, EgyptSchool of Medicine, Newgiza University (NGU), Giza, EgyptCenter of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, EgyptSchool of Medicine, Newgiza University (NGU), Giza, EgyptEndemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, EgyptNational Liver Institute, Menoufia University, Menoufia, EgyptMicrobiology and Immunology Research Program, Children’s Cancer Hospital Egypt 57357, Cairo, EgyptMicrobiology and Immunology Research Program, Children’s Cancer Hospital Egypt 57357, Cairo, EgyptCenter of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, EgyptCenter of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, EgyptEndemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, EgyptNational Liver Institute, Menoufia University, Menoufia, EgyptBiotechnology Graduate Program, American University in New Cairo, Cairo, EgyptDepartment of Biology, American University in Cairo, New Cairo, EgyptSchool of Medicine, Newgiza University (NGU), Giza, EgyptSchool of Medicine, Newgiza University (NGU), Giza, EgyptSchool of Medicine, Newgiza University (NGU), Giza, EgyptIntroductionThe role of miRNAs in regulating variable molecular functions has been sought by scientists for its promising utility in regulating the immune response and, hence, in treating various diseases. In hepatocellular carcinoma (HCC) specifically, a reduction in the number and efficiency of circulating and intrahepatic natural killer (NK) cells has been reported. Our project aims to investigate the role of miR-216a-3p in the regulation of NK cell cytotoxicity, especially since it plays a tumor suppressor role in the context of HCC.MethodsTo achieve our aim, we isolated NK cells from the whole blood of 86 patients with HCC and 23 healthy controls. We assessed the expression profile of miR-216a-3p in NK cells of patients and controls. Furthermore, we induced the expression of miR-216a-3p in NK cells isolated from healthy controls, followed by measuring the release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), perforins (PRF) and granzyme B (GrB) using ELISA as well as NK cells cytolytic activity against Huh7 cells using lactate dehydrogenase (LDH) cytotoxicity assay. After that, we performed an in silico analysis to understand the mechanistic regulation imposed by miR-216a-3p on NK cells to study its impact on one of its potential downstream targets.ResultsOur results have indicated that miR-216a-3p has higher expression in NK cells of patients with HCC, and simulating this elevated expression pattern via forcing miR-216a-3p expression in normal NK cells has negatively impacted the release of TNF- α, IFN- γ, GrB, and PRF. Consequently, a decrease in cell cytolysis was observed. Our in silico analysis revealed that the predicted downstream targets of miR-216a-3p are enriched in the FOXO-signaling pathway. Among those targets is FOXO-1, which has been reported to play a role in NK cell maturation. Thus, we evaluated FOXO-1 expression upon mimicking miR-216a-3p in control NK cells that showed significant downregulation of FOXO-1 on both RNA and protein levels.ConclusionIn conclusion, we report miR-216-3p as a negative regulator of NK cell cytotoxicity.https://www.frontiersin.org/articles/10.3389/fonc.2024.1523068/fullmicroRNAs (miRNAs)miR-216a-3phepatocellular carcinoma (HCC)natural killer (NK) cellstumor necrosis factor-alpha (TNF-alpha)interferon-gamma (IFN-gamma) |
| spellingShingle | Rowan Abdelbary Rowan Abdelbary Manon Ragheb Manon Ragheb Shereen A. El Sobky Nagwa El-Badri Nourhan Aboud Ahmed Tawheed Asmaa Gomaa Mona Zidan Ramy K. Aziz Abd Elrahman Abouzid Radwa Ayman Salah Mohamed El-Kassas Imam Waked Ahmed Moustafa Ahmed Moustafa Injie Omar Fawzy Nada El-Ekiaby Ahmed Ihab Abdelaziz MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells Frontiers in Oncology microRNAs (miRNAs) miR-216a-3p hepatocellular carcinoma (HCC) natural killer (NK) cells tumor necrosis factor-alpha (TNF-alpha) interferon-gamma (IFN-gamma) |
| title | MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells |
| title_full | MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells |
| title_fullStr | MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells |
| title_full_unstemmed | MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells |
| title_short | MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells |
| title_sort | mir 216a 3p inhibits the cytotoxicity of primary natural killer cells |
| topic | microRNAs (miRNAs) miR-216a-3p hepatocellular carcinoma (HCC) natural killer (NK) cells tumor necrosis factor-alpha (TNF-alpha) interferon-gamma (IFN-gamma) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1523068/full |
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