Circ-LRP1B functions as a competing endogenous RNA to regulate proliferation, apoptosis and oxidative stress of LPS-induced human C28/I2 chondrocytes.

Circular RNAs (circRNAs) are crucial for the pathogenesis of human diseases, including osteoarthritis (OA). Here, we set to elucidate the biological action of circ-LRP1B in OA pathogenesis. Human C28/I2 chondrocytes were stimulated by lipopolysaccharide (LPS). Circ-LRP1B, nuclear factor, erythroid 2 like 1 (NRF1) and microRNA (miR)-34a-5p were quantified by quantitative real-time PCR (qRT-PCR) or immunoblotting. Cell viability, proliferation, and apoptosis abilities were gauged by MTT, 5-Ethynyl-2'-Deoxyuridine (EdU) staining, and flow cytometry assays, respectively. Direct relationship between miR-34a-5p and circ-LRP1B or NRF1 was validated by RNA pull-down and dual-luciferase reporter assays. Circ-LRP1B was found to be underexpressed in OA cartilage and LPS-stimulated C28/I2 chondrocytes. Enforced expression of circ-LRP1B promoted cell proliferation, and repressed apoptosis and oxidative stress, as well as impacted OA-specific hallmarks expression of LPS-stimulated C28/I2 cells. NRF1 was identified as a downstream effector of circ-LRP1B function. Moreover, NRF1 was identified as a miR-34a-5p target in LPS-stimulated C28/I2 cells. Circ-LRP1B acted as a competing endogenous RNA (ceRNA) for miR-34a-5p to involve the post-transcriptional regulation of NRF1 expression. Furthermore, the effects of circ-LRP1B overexpression partly depended on the reduction of available miR-34a-5p. These findings demonstrate that circ-LRP1B functions as a ceRNA to regulate the proliferation, apoptosis and oxidative stress of LPS-stimulated human C28/I2 chondrocytes by miR-34a-5p/NRF1 network.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)