Multiple Myeloma

NEAT1[LncRNA]

miR-29b-3p[miRNA]

Sp1[mRNA]

multiple myeloma cells

Homo sapiens (human)

Eur J Pharmacol. 2021 Jan 15;891:173752. doi: 10.1016/j.ejphar.2020.173752. Epub 2020 Nov 28.

Lnc NEAT1/miR-29b-3p/Sp1 form a positive feedback loop and modulate bortezomib resistance in human multiple myeloma cells.

MTT assay;Chromatin immunoprecipitation;Flow Cytometry assay;MTT assay;

The overall survival of multiple myeloma (MM) patients significantly improved with the use of proteasome inhibitor such as bortezomib. However, resistance to sorafenib limits its use. Bortezomib-resistant MM cells were generated and their bortezomib-resistant properties were confirmed by cell viability and apoptosis assays. To explore functions and underlying mechanisms of long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) on bortezomib resistance in MM, MTT assays, flow cytometry analyses, dual luciferase report gene assays, RNA pulldown assays and chromatin immunoprecipitation assays were carried out. NEAT1 and specific protein 1 (Sp1) was upregulated while miR-29b-3p was down regulated in bortezomib-resistant MM cells. NEAT1 promoted Sp1 expression by sponging miR-29b-3p and then enhanced the tolerance of MM cells to bortezomib. Sp1 targeted to NEAT1 promoter region promoting NEAT1 transcription and formed a positive feedback loop. NEAT1 and Sp1 levels were higher and miR-29b-3p was levels were lower in bortezomib-resistant MM patients. NEAT1/miR-29b-3p/Sp1 feedback loop enhanced the tolerance of MM cells to bortezomib. These results indicate potentially valuable targets for overcoming bortezomib resistance for MM.