Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axis

Objectives: Circ_003686 is a novel_circRNA with abnormally low expression found in the samples of multiple myeloma bone disease (MBD) patients. The current research intended to investigate the effects of novel_circ_003686 in osteogenesis-induced differentiation of bone marrow mesenchymal stem cells...

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Main Authors: Ling Qiu, Lei Ma, Dan Chen, Nan Zhang, Jiao Cai, Qian Zhang, Xiao Wang, Hai Yi, Hao Yao, Fang-Yi Fan
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Journal of Bone Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2212137423000428
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author Ling Qiu
Lei Ma
Dan Chen
Nan Zhang
Jiao Cai
Qian Zhang
Xiao Wang
Hai Yi
Hao Yao
Fang-Yi Fan
author_facet Ling Qiu
Lei Ma
Dan Chen
Nan Zhang
Jiao Cai
Qian Zhang
Xiao Wang
Hai Yi
Hao Yao
Fang-Yi Fan
author_sort Ling Qiu
collection DOAJ
description Objectives: Circ_003686 is a novel_circRNA with abnormally low expression found in the samples of multiple myeloma bone disease (MBD) patients. The current research intended to investigate the effects of novel_circ_003686 in osteogenesis-induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in MBD. Methods: BMSCs were extracted from MBD patients and normal participants, the pcDNA3.1 encoding the circ_003686 (ov-circ_003686), miR-142-5p-mimic/inhibitor and siRNA oligonucleotides targeting insulin like growth factor 1 (IGF1, si-IGF1) were applied to intervene circ_003686, miR-142-5p and IGF1 levels, respectively. Results: Results showed that ov-circ_003686 could mediate the osteogenesis-induced differentiation of MBD-BMSC, and luciferase assay and RIP experiments confirmed that circ_003686 could bind to miR-142-5p. MiR-142-5p-inhibitor helped osteogenesis-induced differentiation, while miR-142-5p-mimic inhibited osteogenesis-induced differentiation and reversed the promoting effect of ov-circ_003686, suggesting that circ_003686/miR-142-5p axis participated in osteogenesis-induced differentiation of MBD-BMSC. In addition, miR-142-5p binds to the target gene IGF1 and negatively adjust its expression. Si-IGF1 significantly inhibited the osteogenesis-induced differentiation and reversed the promotion effects of miR-142-5p-inhibitor and ov-circ_003686. Moreover, circ_003686/miR-142-5p/IGF1 axis meaningfully regulates protein expressions in the PI3K/AKT pathway. Conclusion: In conclusion, this research confirmed that circ_003686 regulated the osteogenesis-induced differentiation of MBD-BMSC by sponging miR-142-5p and mediating IGF1, and the PI3K/AKT pathway may also be involved.
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spelling doaj.art-4d53983fd950438c8b032bfa7256d5762023-12-15T07:23:58ZengElsevierJournal of Bone Oncology2212-13742023-12-0143100509Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axisLing Qiu0Lei Ma1Dan Chen2Nan Zhang3Jiao Cai4Qian Zhang5Xiao Wang6Hai Yi7Hao Yao8Fang-Yi Fan9Department of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaDepartment of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaDepartment of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaDepartment of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaDepartment of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaDepartment of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaDepartment of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaDepartment of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaCorresponding authors.; Department of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaCorresponding authors.; Department of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People’s Liberation Army Western Theatre, Chengdu, SiChuan, ChinaObjectives: Circ_003686 is a novel_circRNA with abnormally low expression found in the samples of multiple myeloma bone disease (MBD) patients. The current research intended to investigate the effects of novel_circ_003686 in osteogenesis-induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in MBD. Methods: BMSCs were extracted from MBD patients and normal participants, the pcDNA3.1 encoding the circ_003686 (ov-circ_003686), miR-142-5p-mimic/inhibitor and siRNA oligonucleotides targeting insulin like growth factor 1 (IGF1, si-IGF1) were applied to intervene circ_003686, miR-142-5p and IGF1 levels, respectively. Results: Results showed that ov-circ_003686 could mediate the osteogenesis-induced differentiation of MBD-BMSC, and luciferase assay and RIP experiments confirmed that circ_003686 could bind to miR-142-5p. MiR-142-5p-inhibitor helped osteogenesis-induced differentiation, while miR-142-5p-mimic inhibited osteogenesis-induced differentiation and reversed the promoting effect of ov-circ_003686, suggesting that circ_003686/miR-142-5p axis participated in osteogenesis-induced differentiation of MBD-BMSC. In addition, miR-142-5p binds to the target gene IGF1 and negatively adjust its expression. Si-IGF1 significantly inhibited the osteogenesis-induced differentiation and reversed the promotion effects of miR-142-5p-inhibitor and ov-circ_003686. Moreover, circ_003686/miR-142-5p/IGF1 axis meaningfully regulates protein expressions in the PI3K/AKT pathway. Conclusion: In conclusion, this research confirmed that circ_003686 regulated the osteogenesis-induced differentiation of MBD-BMSC by sponging miR-142-5p and mediating IGF1, and the PI3K/AKT pathway may also be involved.http://www.sciencedirect.com/science/article/pii/S2212137423000428Novel_circ_003686miR-142-5pIGF1Multiple myeloma bone diseaseBone marrow mesenchymal stem cellsOsteogenesis-induced differentiation
spellingShingle Ling Qiu
Lei Ma
Dan Chen
Nan Zhang
Jiao Cai
Qian Zhang
Xiao Wang
Hai Yi
Hao Yao
Fang-Yi Fan
Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axis
Journal of Bone Oncology
Novel_circ_003686
miR-142-5p
IGF1
Multiple myeloma bone disease
Bone marrow mesenchymal stem cells
Osteogenesis-induced differentiation
title Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axis
title_full Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axis
title_fullStr Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axis
title_full_unstemmed Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axis
title_short Novel_circ_003686 regulates the osteogenic differentiation of MSCs in patients with myeloma bone disease through miR-142-5p/IGF1 axis
title_sort novel circ 003686 regulates the osteogenic differentiation of mscs in patients with myeloma bone disease through mir 142 5p igf1 axis
topic Novel_circ_003686
miR-142-5p
IGF1
Multiple myeloma bone disease
Bone marrow mesenchymal stem cells
Osteogenesis-induced differentiation
url http://www.sciencedirect.com/science/article/pii/S2212137423000428
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