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

Ling Qiu; Lei Ma; Dan Chen; Nan Zhang; Jiao Cai; Qian Zhang; Xiao Wang; Hai Yi; Hao Yao; Fang-Yi Fan

doi:10.1016/j.jbo.2023.100509

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

J Bone Oncol. 2023 Nov 3:43:100509. doi: 10.1016/j.jbo.2023.100509. eCollection 2023 Dec.

Authors

Ling Qiu¹, Lei Ma¹, Dan Chen¹, Nan Zhang¹, Jiao Cai¹, Qian Zhang¹, Xiao Wang¹, Hai Yi¹, Hao Yao¹, Fang-Yi Fan¹

Affiliation

¹ Department of Hematology and Hematopoietic Stem Cell Transplantation Center, General Hospital of the Chinese People's Liberation Army Western Theatre, Chengdu, SiChuan, China.

Abstract

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.

Keywords: Bone marrow mesenchymal stem cells; IGF1; Multiple myeloma bone disease; Novel_circ_003686; Osteogenesis-induced differentiation; miR-142-5p.