Hsa_Circ_0134426 Attenuates the Malignant Biological Behaviors of Multiple Myeloma by Suppressing miR-146b-3p to Upregulate NDNF.

Abstract

We focused on hsa_circ_0134426 (circ_0134426) to determine its functional effects and targets in multiple myeloma (MM) development. The relative expression of circ_0134426, miR-146b-3p, and neuron-derived neurotrophic factor (NDNF) in the MM samples was confirmed by quantitative real-time PCR (qPCR) or western blotting. The protein levels of epithelial-to-mesenchymal transition (EMT)-linked markers were identified using western blotting. Xenograft models in nude mice were used for in vivo functional analysis of circ_0134426. The binding of miR-146b-3p to circ_0134426 or NDNF was confirmed by dual-luciferase and RIP assays. Poor levels of circ_0134426 and NDNF and high levels of miR-146b-3p were observed in MM bone marrow samples and cell lines. Circ_0134426 overexpression blocked MM cell growth, colony formation, and migration and impeded tumor development in xenograft models. circRNA_0134426 decoys miR-146b-3p to repress its expression. Overexpression of miR-146b-3p restored MM cell activities that were blocked by circ_0134426 overexpression. NDNF is a functional molecule targeted by miR-146b-3p, and miR-146b-3p sequesters NDNF expression. The inhibitory effects of NDNF upregulation on MM cell growth, colony formation, and migration were partially abolished by miR-146b-3p overexpression. Circ_0134426 regulates the miR-146b-3p/NDNF network to restrain the development of MM, to some extent, suggesting that the development of MM therapeutic strategies might focus on circ_0134426 regulatory networks.