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miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1
OBJECTIVE: To study the effect of miR-138 on the function of osteosarcoma (OS) T follicular helper cells (Tfh cells) and its mechanism. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with osteosarcoma (OS group) and healthy volunteers (control group). CD4+CXCR5+ Tfh...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691981/ https://www.ncbi.nlm.nih.gov/pubmed/34950224 http://dx.doi.org/10.1155/2021/2895893 |
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author | Jiang, Baoen Kang, Xiuqin Zhao, Gang Lu, Jianshu Wang, Zhitao |
author_facet | Jiang, Baoen Kang, Xiuqin Zhao, Gang Lu, Jianshu Wang, Zhitao |
author_sort | Jiang, Baoen |
collection | PubMed |
description | OBJECTIVE: To study the effect of miR-138 on the function of osteosarcoma (OS) T follicular helper cells (Tfh cells) and its mechanism. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with osteosarcoma (OS group) and healthy volunteers (control group). CD4+CXCR5+ Tfh cells and CD9+ B cells were sorted by flow cytometry. qRT-PCR was used to detect the expression of miR-138 and PDK1 in the peripheral blood and CD4+CXCR5+ Tfh cells. Flow cytometry was employed to detect the proportion of CD4+CXCR5+ Tfh cells in CD4+ T cells, the level of CD40L in CD4+CXCR5+ Tfh cells, and the expression of CD27 and CD38 in B cells. Western blot was used to determine the protein expression of PDK1, PI3K, p-Akt, Akt, p-mTOR, and mTOR. In addition, dual-luciferase reporter assay was performed to verify the relationship between miR-138 and PDK1. ELISA method was used to determine the levels of IgM, IgG, IL-10, and IL-21. RESULTS: Compared with that of the control group, the expression of miR-138 in PBMC and CD4+CXCR5+ Tfh cells of the OS group was lower; overexpression of miR-138 could promote the maturation of Tfh cells and immature B cells. The results of the dual-luciferase report experiment showed that miR-138 can target and negatively regulate PDK1, and PDK1 can reverse the effect of miR-138 on the function of Tfh cells and immature B cells. CONCLUSION: miR-138 inhibits the PI3K/Akt/mTOR pathway by targeting and negatively regulating PDK1 to alleviate the dysfunction of T follicular helper cells in OS. |
format | Online Article Text |
id | pubmed-8691981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-86919812021-12-22 miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1 Jiang, Baoen Kang, Xiuqin Zhao, Gang Lu, Jianshu Wang, Zhitao Comput Math Methods Med Research Article OBJECTIVE: To study the effect of miR-138 on the function of osteosarcoma (OS) T follicular helper cells (Tfh cells) and its mechanism. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with osteosarcoma (OS group) and healthy volunteers (control group). CD4+CXCR5+ Tfh cells and CD9+ B cells were sorted by flow cytometry. qRT-PCR was used to detect the expression of miR-138 and PDK1 in the peripheral blood and CD4+CXCR5+ Tfh cells. Flow cytometry was employed to detect the proportion of CD4+CXCR5+ Tfh cells in CD4+ T cells, the level of CD40L in CD4+CXCR5+ Tfh cells, and the expression of CD27 and CD38 in B cells. Western blot was used to determine the protein expression of PDK1, PI3K, p-Akt, Akt, p-mTOR, and mTOR. In addition, dual-luciferase reporter assay was performed to verify the relationship between miR-138 and PDK1. ELISA method was used to determine the levels of IgM, IgG, IL-10, and IL-21. RESULTS: Compared with that of the control group, the expression of miR-138 in PBMC and CD4+CXCR5+ Tfh cells of the OS group was lower; overexpression of miR-138 could promote the maturation of Tfh cells and immature B cells. The results of the dual-luciferase report experiment showed that miR-138 can target and negatively regulate PDK1, and PDK1 can reverse the effect of miR-138 on the function of Tfh cells and immature B cells. CONCLUSION: miR-138 inhibits the PI3K/Akt/mTOR pathway by targeting and negatively regulating PDK1 to alleviate the dysfunction of T follicular helper cells in OS. Hindawi 2021-12-14 /pmc/articles/PMC8691981/ /pubmed/34950224 http://dx.doi.org/10.1155/2021/2895893 Text en Copyright © 2021 Baoen Jiang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Jiang, Baoen Kang, Xiuqin Zhao, Gang Lu, Jianshu Wang, Zhitao miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1 |
title | miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1 |
title_full | miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1 |
title_fullStr | miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1 |
title_full_unstemmed | miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1 |
title_short | miR-138 Reduces the Dysfunction of T Follicular Helper Cells in Osteosarcoma via the PI3K/Akt/mTOR Pathway by Targeting PDK1 |
title_sort | mir-138 reduces the dysfunction of t follicular helper cells in osteosarcoma via the pi3k/akt/mtor pathway by targeting pdk1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691981/ https://www.ncbi.nlm.nih.gov/pubmed/34950224 http://dx.doi.org/10.1155/2021/2895893 |
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