Investigation of Non-Coding RNA-Related Autophagy Alterations in Drug-Resistant Multiple Myeloma Plasma Cells.

Background & objective: Multiple myeloma (MM) drug resistance is thought to be caused by the development of protective autophagy. This work aimed to assess the non-coding RNA (ncRNA) autophagy-related alterations in drug-resistant (DR) myeloma cells.

Methods: DR Plasma cells were extracted from the bone marrow of DR patients referred to Baghai 2 Hospital in Ahvaz, Iran. The cells were grown in RPMI-1640 media containing 10% FBS and 1% Pen/Strep and incubated at 37˚C and 5% CO₂. After six passages, the plasma cells were precisely isolated and utilized as DR cells. The U266B1 cell line (IBRC C10148) was grown in the RPMI-1640 media containing 10% FBS and 1% Pen/Strep and utilized as drug-sensitive (DS) cells. The relative expression of the genes was determined using the Real-time PCR method. Statistical analysis of the data was performed using GraphPad Prism 8 software.

Results: When the DR cells were compared to the DS cells, there was a notable increase in the expression of ULK1 and LC3B. However, expression of P62 in the DR plasma cells showed a significant decrease compared to the DS plasma cells. The miR-1297 level was considerably higher in the DR cells than in the DS cells. Although, there was no statistically significant difference in the expression of miR-26a-5p between the DS and DR cells. The DR cells exhibited a statistically significant increase in the expression of MALAT1 and SNHG6.

Conclusion: Drug resistance in MM cells may result from overexpression of non-coding RNAs involved in autophagy.