Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma

Sicheng Bian; Sicheng Bian; Xialin Zhang; Leilei Lin; Lili Sun; Lili Sun; Zhibo Guo; Zhibo Guo; Jie Pan; Jiangxia Cui; Hanbing Yao; Jing Xu; Zhuanghui Hao; Yuzhu Wang; Yuzhu Wang; Liguo Tong; Xingpeng Bu; Desheng Kong; Nianjiao Liu; Yinghua Li; Yinghua Li

doi:10.3389/fonc.2022.978755

Frontiers in Oncology (Aug 2022)

Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma

Sicheng Bian,
Sicheng Bian,
Xialin Zhang,
Leilei Lin,
Lili Sun,
Lili Sun,
Zhibo Guo,
Zhibo Guo,
Jie Pan,
Jiangxia Cui,
Hanbing Yao,
Jing Xu,
Zhuanghui Hao,
Yuzhu Wang,
Yuzhu Wang,
Liguo Tong,
Xingpeng Bu,
Desheng Kong,
Nianjiao Liu,
Yinghua Li,
Yinghua Li

Affiliations

Sicheng Bian: Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
Sicheng Bian: Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
Xialin Zhang: Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
Leilei Lin: Department of Hematology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
Lili Sun: Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
Lili Sun: Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
Zhibo Guo: Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
Zhibo Guo: Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
Jie Pan: Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, United States
Jiangxia Cui: Department of Hematology, Xi’an International Medical Center Hospital, Xi’an, China
Hanbing Yao: Department of Hematology, Xi’an International Medical Center Hospital, Xi’an, China
Jing Xu: Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China
Zhuanghui Hao: Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China
Yuzhu Wang: Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
Yuzhu Wang: Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
Liguo Tong: Central Laboratory, Shanxi Academy of Traditional Chinese Medicine, Taiyuan, China
Xingpeng Bu: Department of Geriatrics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
Desheng Kong: Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
Nianjiao Liu: Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
Yinghua Li: Key Laboratory of Cell Transplantation of National Health Commission, Heilongjiang Key Laboratory of Blood and Hematopoietic System, Harbin Medical University, Harbin, China
Yinghua Li: Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China

DOI: https://doi.org/10.3389/fonc.2022.978755
Journal volume & issue: Vol. 12

Abstract

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BackgroundHypercalcemia 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.MethodsA 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 Ca2+-ATPase 4 (PMCA4) in RBCs.ResultsThe 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.ConclusionsStudies 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.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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