NORAD promotes multiple myeloma cell progression via BMP6/P-ERK1/2 axis

• Published in: Cellular signalling Vol. 100; p. 110474
• Main Authors: Ma, Tao, Chen, Yan, Yi, Zhi-Gang, Liu, Jia, Li, Yan-Hong, Bai, Jun, Tie, Wen-Ting, Huang, Mei, Zhu, Xiao-Feng, Wang, Ji, Du, Juan, Zuo, Xiu-Qin, Li, Qin, Lin, Fan-Li, Tang, Liu, Guo, Jing, Xiao, Hong-Wen, Lei, Qian, Ma, Xiao-Li, Li, Li-Juan, Zhang, Lian-Sheng
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.12.2022
• Subjects: Apoptosis; BMP6; Cell cycle; Multiple myeloma; NORAD; Proliferation; Proliferation; NORAD; BMP6; Multiple myeloma; Cell cycle; Apoptosis
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2022.110474

Multiple myeloma (MM) is one of the most common tumors of the hematological system and remains incurable. Recent studies have shown that long noncoding RNA NORAD is a potential oncogene in a variety of tumors. However, the general biological role and clinical value of NORAD in MM remains unknown. In this study, we measured NORAD expression in bone marrow of 60 newly diagnosed MM, 30 post treatment MM and 17 healthy donors by real-time quantitative polymerase chain reaction (qPCR). The NORAD gene was knockdown by lentiviral transfection in MM cell lines, and the effects of NORAD on apoptosis, cell cycle and cell proliferation in MM cells were examined by flow cytometry, CCK8 assay, EDU assay and Western blot, and the differential genes after knockdown of NORAD were screened by mRNA sequencing, followed by in vivo experiments and immunohistochemical assays. We found that knockdown of NORAD promoted MM cell apoptosis, induced cell cycle G1 phase arrest, and inhibited MM cell apoptosis in in vivo and in vitro experiments. Mechanistically, NORAD plays these roles through the BMP6/P-ERK1/2 axis. We discuss a novel mechanism by which NORAD acts pro-tumorigenically in MM via the BMP6/P-ERK1/2 axis.