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Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R

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Abstract

In recent years, some studies have been made on the effects of circular RNA (circRNA) in osteoarthritis (OA) and so on; however, its mechanisms remain to be further explored. Studies have shown that tumor necrosis factor-alpha can inhibit hsa_circ_0045714 expression in chondrocytes so as to upregulate miR-193b expression. Dual-luciferase reporter assay showed that insulin-like growth factor 1 receptor (IGF1R) is a key target gene of miR-193b. Hsa_circ_0045714 over-expression does not influence miR-193b expression, but can inhibit its transcriptional activity, thereby upregulating IGF1R expression. Hsa_circ_0045714 can promote the expression of type II collagen and aggrecan, and upregulate chondrocyte proliferation, while its linear sequences cannot. IGF1R has similar function, while miR-193b can inhibit the expression of type II collagen and aggrecan, and downregulate chondrocyte proliferation but enhance their apoptosis. IGF1R overexpression can reverse the effect of miR-193b, while miR-193b mimics or IGF1R siRNA can inhibit the function of hsa_circ_0045714. Therefore, hsa_circ_0045714 can regulate extracellular matrix synthesis as well as proliferation and apoptosis of chondrocytes by promoting the expression of miR-193b target gene IGF1R. The findings will provide new proofs for studies on the applications of circRNA in OA and other orthopedic diseases.

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Acknowledgements

This study was supported by Natural Science Foundation of Guangdong Province, China (No.: 2015A030313611).

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Correspondence to Hong Xia or Bei Chen.

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Li, Bf., Zhang, Y., Xiao, J. et al. Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R. Human Cell 30, 311–318 (2017). https://doi.org/10.1007/s13577-017-0177-7

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  • DOI: https://doi.org/10.1007/s13577-017-0177-7

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