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

Autor: Ling Qiu, Lei Ma, Dan Chen, Nan Zhang, Jiao Cai, Qian Zhang, Xiao Wang, Hai Yi, Hao Yao, Fang-Yi Fan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Bone Oncology, Vol 43, Iss , Pp 100509- (2023)
Druh dokumentu: article
ISSN: 2212-1374
DOI: 10.1016/j.jbo.2023.100509
Popis: 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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