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

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.