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

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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.

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Authors and Affiliations

  1. Department of Hematology, Taikang Tongji (Wuhan)Hospital, No. 322, Sixin North Road, Hanyang District, Wuhan, 430050, Hubei, China

    Menglan Li, Jingyuan Li & Yanyan Song

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Contributions

MLL and JYL: performed the experiments and data analysis. YYS and MLL: conceived and designed the study. YYS and JYL: made the acquisition of data. YYS and MLL: did the analysis and interpretation of data. All authors read and approved the manuscript.

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Correspondence to Yanyan Song.

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Research involving Human Participants and/or Animals

The present study was approved by the Ethics Committee of Taikang Tongji (Wuhan)Hospital (Wuhan, China). The processing of clinical tissue samples is in strict compliance with the ethical standards of the Declaration of Helsinki. All patients signed written informed consent. This animal experiment was conducted in accordance with the ARRIVE guidelines and was authorized by the Ethics Committee of Taikang Tongji (Wuhan)Hospital.

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Li, M., Li, J. & Song, Y. Hsa_Circ_0134426 Attenuates the Malignant Biological Behaviors of Multiple Myeloma by Suppressing miR-146b-3p to Upregulate NDNF. Mol Biotechnol 65, 1165–1177 (2023). https://doi.org/10.1007/s12033-022-00618-6

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