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Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma
BACKGROUND: Hypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood. METHODS: A total of 113 patients with MM osteolytic lesions w...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458875/ https://www.ncbi.nlm.nih.gov/pubmed/36091107 http://dx.doi.org/10.3389/fonc.2022.978755 |
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author | Bian, Sicheng Zhang, Xialin Lin, Leilei Sun, Lili Guo, Zhibo Pan, Jie Cui, Jiangxia Yao, Hanbing Xu, Jing Hao, Zhuanghui Wang, Yuzhu Tong, Liguo Bu, Xingpeng Kong, Desheng Liu, Nianjiao Li, Yinghua |
author_facet | Bian, Sicheng Zhang, Xialin Lin, Leilei Sun, Lili Guo, Zhibo Pan, Jie Cui, Jiangxia Yao, Hanbing Xu, Jing Hao, Zhuanghui Wang, Yuzhu Tong, Liguo Bu, Xingpeng Kong, Desheng Liu, Nianjiao Li, Yinghua |
author_sort | Bian, Sicheng |
collection | PubMed |
description | BACKGROUND: Hypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood. METHODS: A total of 113 patients with MM osteolytic lesions were studied retrospectively. Flow cytometry and atomic absorption spectroscopy were used to detect calcium content. Immunofluorescence and Western blotting were used to investigate protein expression. GEO and miRNA databases were used to screen miRNAs. Exosomal miR-4261 migration was investigated by Transwell assay. Dual-luciferase assays confirmed the targeting relationship between miR-4261 and ATP2B4. An RBC oxidative stress model was constructed, and Omega-Agatoxin IVA was used to study the role of plasma membrane Ca(2+)-ATPase 4 (PMCA4) in RBCs. RESULTS: The results showed that MM RBCs had calcium overload, and serum calcium levels increased as the number of RBCs decreased. The expression of PMCA4 in MM RBCs was significantly lower than in normal RBCs. The exosomal miR-4261 produced by MM cells could be transferred to RBCs to downregulate the expression of ATP2B4. CONCLUSIONS: Studies have confirmed that RBCs experience calcium overload in MM with osteolytic lesions, which is related to the downregulation of ATP2B4 by MM exosomal miR-4261. |
format | Online Article Text |
id | pubmed-9458875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94588752022-09-10 Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma Bian, Sicheng Zhang, Xialin Lin, Leilei Sun, Lili Guo, Zhibo Pan, Jie Cui, Jiangxia Yao, Hanbing Xu, Jing Hao, Zhuanghui Wang, Yuzhu Tong, Liguo Bu, Xingpeng Kong, Desheng Liu, Nianjiao Li, Yinghua Front Oncol Oncology BACKGROUND: Hypercalcemia induced by multiple myeloma (MM) affects the biological functions of excitable and non-excitable cells. However, red blood cells (RBCs) regulatory effect on calcium in hypercalcemia is still not fully understood. METHODS: A total of 113 patients with MM osteolytic lesions were studied retrospectively. Flow cytometry and atomic absorption spectroscopy were used to detect calcium content. Immunofluorescence and Western blotting were used to investigate protein expression. GEO and miRNA databases were used to screen miRNAs. Exosomal miR-4261 migration was investigated by Transwell assay. Dual-luciferase assays confirmed the targeting relationship between miR-4261 and ATP2B4. An RBC oxidative stress model was constructed, and Omega-Agatoxin IVA was used to study the role of plasma membrane Ca(2+)-ATPase 4 (PMCA4) in RBCs. RESULTS: The results showed that MM RBCs had calcium overload, and serum calcium levels increased as the number of RBCs decreased. The expression of PMCA4 in MM RBCs was significantly lower than in normal RBCs. The exosomal miR-4261 produced by MM cells could be transferred to RBCs to downregulate the expression of ATP2B4. CONCLUSIONS: Studies have confirmed that RBCs experience calcium overload in MM with osteolytic lesions, which is related to the downregulation of ATP2B4 by MM exosomal miR-4261. Frontiers Media S.A. 2022-08-26 /pmc/articles/PMC9458875/ /pubmed/36091107 http://dx.doi.org/10.3389/fonc.2022.978755 Text en Copyright © 2022 Bian, Zhang, Lin, Sun, Guo, Pan, Cui, Yao, Xu, Hao, Wang, Tong, Bu, Kong, Liu and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Bian, Sicheng Zhang, Xialin Lin, Leilei Sun, Lili Guo, Zhibo Pan, Jie Cui, Jiangxia Yao, Hanbing Xu, Jing Hao, Zhuanghui Wang, Yuzhu Tong, Liguo Bu, Xingpeng Kong, Desheng Liu, Nianjiao Li, Yinghua Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma |
title | Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma |
title_full | Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma |
title_fullStr | Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma |
title_full_unstemmed | Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma |
title_short | Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma |
title_sort | exosomal mir-4261 mediates calcium overload in rbcs by downregulating the expression of atp2b4 in multiple myeloma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458875/ https://www.ncbi.nlm.nih.gov/pubmed/36091107 http://dx.doi.org/10.3389/fonc.2022.978755 |
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