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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Multiple myeloma (MM) treatment improved with proteasome inhibitors like bortezomib.
• Drug resistance, particularly to bortezomib, remains a significant clinical challenge in MM management.

Purpose of the Study:

• To investigate the role of the long non-coding RNA NEAT1 in mediating bortezomib resistance in multiple myeloma.
• To elucidate the molecular mechanisms underlying NEAT1's function in drug-resistant MM cells.

Main Methods:

• Generation and characterization of bortezomib-resistant MM cell lines.
• Assays included MTT, flow cytometry, dual luciferase reporter, RNA pulldown, and chromatin immunoprecipitation.
• Analysis of NEAT1, Sp1, and miR-29b-3p expression levels in cell lines and patient samples.

Main Results:

• NEAT1 and Sp1 were upregulated, while miR-29b-3p was downregulated in bortezomib-resistant MM cells and patients.
• NEAT1 promoted Sp1 expression by sponging miR-29b-3p, enhancing MM cell tolerance to bortezomib.
• A positive feedback loop was identified where Sp1 enhances NEAT1 transcription, further contributing to drug resistance.

Conclusions:

• The NEAT1/miR-29b-3p/Sp1 feedback loop plays a critical role in conferring bortezomib resistance in multiple myeloma.
• This regulatory axis represents a potential therapeutic target for overcoming bortezomib resistance in MM patients.