The Mitochondrial Protease LonP1 Promotes Proteasome Inhibitor Resistance in Multiple Myeloma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Mitochondrial Proteases in Multiple Myeloma
2.2. Regulation of LONP1 and OSGEPL1 Genes in Multiple Myeloma Cells
2.3. The Interplay of LonP1 and Proteasome Activities in Multiple Myeloma Cells
3. Discussion
4. Materials and Methods
4.1. Survival Analysis
4.2. Drug Treatments
4.3. Transcript Analysis
- β-actin (F-5’-CATGTACGTTGCTATCCAGGC; R-5′-CTCCTTAATGTCACGCACGAT);
- LONP1 (F-5′-ATGGAGGACGTCAAGAAACG; R-5′-GATCTCAGCCACGTCAGTCA);
- OSGEPL1 (F-5′-AAAACAGGTGGGATTGTTCCTC; R-5′-AGTAAGTGCATGAGCCTCCAT);
- CD40 (F-5′-ACTGAAACGGAATGCCTTCCT; R-5′-CCTCACTCGTACAGTGCCA);
- COX2 (F-5′-TAAGTGCGATTGTACCCGGAC; R-5′-TTTGTAGCCATAGTCAGCATTGT);
- ICAM-1 (F-5′-ATGCCCAGACATCTGTGTCC; R-5′-GGGGTCTCTATGCCCAACAA);
- IL-6 (F-5′-CCTGAACCTTCCAAAGATGGC; R-5′-TTCACCAGGCAAGTCTCCTCA);
- IRF3 (F-5′-AGAGGCTCGTGATGGTCAAG; R-5′-AGGTCCACAGTATTCTCCAGG).
4.4. Computational Modeling
4.5. Cytotoxicity Assays
4.6. Generation of Transgenic MM.1S and MOLP-8 Cells
4.7. Microscopy
4.8. Immunoblotting
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Maneix, L.; Sweeney, M.A.; Lee, S.; Iakova, P.; Moree, S.E.; Sahin, E.; Lulla, P.; Yellapragada, S.V.; Tsai, F.T.F.; Catic, A. The Mitochondrial Protease LonP1 Promotes Proteasome Inhibitor Resistance in Multiple Myeloma. Cancers 2021, 13, 843. https://doi.org/10.3390/cancers13040843
Maneix L, Sweeney MA, Lee S, Iakova P, Moree SE, Sahin E, Lulla P, Yellapragada SV, Tsai FTF, Catic A. The Mitochondrial Protease LonP1 Promotes Proteasome Inhibitor Resistance in Multiple Myeloma. Cancers. 2021; 13(4):843. https://doi.org/10.3390/cancers13040843
Chicago/Turabian StyleManeix, Laure, Melanie A. Sweeney, Sukyeong Lee, Polina Iakova, Shannon E. Moree, Ergun Sahin, Premal Lulla, Sarvari V. Yellapragada, Francis T. F. Tsai, and Andre Catic. 2021. "The Mitochondrial Protease LonP1 Promotes Proteasome Inhibitor Resistance in Multiple Myeloma" Cancers 13, no. 4: 843. https://doi.org/10.3390/cancers13040843