NBR2/miR-561-5p/DLC1 axis inhibited the development of multiple myeloma by activating the AMPK/mTOR pathway to repress glycolysis

 Chang-Sheng Wang, Xiao-Bo Zhang, Xi-Tian Zhu, Rong-Sheng Chen

Abstract:

Long non-coding RNA NBR2 exerts a tumor-suppressive effect in a variety of cancers, but its role in multiple myeloma (MM) is unclear. This article will elucidate the role of NBR2 in MM. The expressions of NBR2, miR-561-5p, and deleted in liver cancer 1 (DLC1) in MM cell lines were determined by quantitative real time polymerase chain reaction (qRT-PCR). The regulatory relationship of the NBR2/miR-561-5p/DLC1 axis was predicted by bioinformatics and confirmed via a dual-luciferase reporter assay. The effect of NBR2 on the biological behavior of MM cells was verified by loss- and gain-of-function experiments (cell counting kit-8, colony formation, flow cytometry, extracellular acidification rate, and lactate production measurement). The effects of the NBR2/miR-561-5p axis on the biological behavior of MM cells, the activation of the AMPK/mTOR signaling pathway (western blot), and DLC1 expression (western blot) were verified by rescue experiments. The upregulation of NBR2 in MM cell lines induced a decrease in the viability, proliferation capacity, glycolysis, and lactic acid production, and an increase in apoptosis of MM cells. NBR2 regulated the biological behavior of MM cells and the activation of the AMPK/mTOR signaling pathway by targeting miR-561-5p. DLC1 was the target gene of miR-561-5p and the protein expression of DLC1 was regulated by the NBR2/miR-561-5p axis. Collectively, NBR2/miR-561-5p/DLC1 axis inhibits the development of MM by activating the AMPK/mTOR pathway to repress glycolysis.