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Investigation of Non-Coding RNA-Related Autophagy Alterations in Drug-Resistant Multiple Myeloma Plasma Cells
Leila Sarafraznia1,2, Zari Tahan Nejad Asadi1,2, Dian Dayer3
1Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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.
Insights
Drug resistance in multiple myeloma (MM) may stem from protective autophagy. This study found that non-coding RNAs (ncRNAs) like miR-1297, MALAT1, and SNHG6 are upregulated in drug-resistant (DR) MM cells, potentially driving this resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multiple myeloma (MM) drug resistance is a significant clinical challenge.
- Protective autophagy is implicated as a key mechanism in the development of MM drug resistance.
Purpose of the Study:
- To investigate the role of non-coding RNAs (ncRNAs) in autophagy-related alterations in drug-resistant (DR) myeloma cells.
- To identify specific ncRNAs associated with drug resistance in MM.
Main Methods:
- Drug-resistant (DR) plasma cells were isolated from MM patients and compared with drug-sensitive (DS) U266B1 cell line.
- Gene expression levels of autophagy-related genes (ULK1, LC3B, P62) and ncRNAs (miR-1297, miR-26a-5p, MALAT1, SNHG6) were analyzed using Real-time PCR.
Main Results:
- DR myeloma cells showed increased expression of autophagy markers ULK1 and LC3B, and decreased expression of P62 compared to DS cells.
- The expression of miR-1297, MALAT1, and SNHG6 was significantly higher in DR cells.
- No significant difference in miR-26a-5p expression was observed between DR and DS cells.
Conclusions:
- Overexpression of specific non-coding RNAs involved in autophagy may contribute to drug resistance in multiple myeloma.
- Targeting these ncRNAs could be a potential therapeutic strategy for overcoming MM drug resistance.
