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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...

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Autores principales: Jiang, Baoen, Kang, Xiuqin, Zhao, Gang, Lu, Jianshu, Wang, Zhitao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
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.
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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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