Akademik Veri Yönetim Sistemi
the 21st AEK Cancer Congress , Kassel, Almanya, 15 - 17 Şubat 2023, ss.83
INVESTIGATION OF THE ROLE OF KDELR1 GENE IN MULTIPLE MYELOMA CELL
LINES
(Poster sunumu, #88)
Şeyma Punar, Burcu Salman-Yaylaz, Berk İleri,Sema Sirma-Ekmekci, Neslihan Abaci
1Aziz Sancar Institute of Experimental Medicine- Institute o f Graduate Studies in Health Sciences-
Istanbul University, Genetics, Istanbul, Turkiye
Purpose: Multiple myeloma (MM) ranks second among hematological malignancies. The
uncontrolled proliferation of monoclonal plasma cells in the bone marrow is characterized by the
overproduction and accumulation of nonfunctional immunoglobulins or immunoglobulin chains in
the cells. Therefore, protein transport plays an important role in this disease. KDELR1 encodes an
integral membrane protein with seven transmembrane domains and acts as a receptor. It is involved
in the packaging of KDEL motif proteins into COPI vesicles for COPI-mediated retrograde transport. In
our previous studies, we have shown that KDELR1 and COPE gene expressions are increased in MM
patients compared to control. In this study, we aim to examine the effect of siRNA mediated
suppression of KDELR1 gene expression on cell proliferation, apoptosis, and coatomer genes in U266
and RPMI8226 cell lines.
Methods: In our study, to understand the effect of KDELR1 in MM, gene expression in U266 and
RPMI8226 cells was suppressed by siRNA.The KDELR1 protein level change was shown by western
blot analysis. Cells stained with fluorescent dye were visualized under a confocal laser scanning
microscope to determıne apoptosis in the control and KDELR1 siRNA treated groups. The proportions
of apoptotic and viable cells were calculated with the ImageJ program.MTT test was applied to
determine its effect on cell proliferation. To understand the effect of suppression of the KDELR1 on
the formation of coataomers; The expression changes of COPE, COPA, COPB1, COPD and COPZ1
genes, which are the coatomer components, were determined by qRT-PCR method.
Results: The KDELR1 gene was suppressed by 80% at 24 hours and 74% at 48 hours in U266 cells. In
RPMI8226 cells, it was suppressed by 85% in 24th hour and 75% in 48th hour. When the expression
level of the coatomer genes in the cells in which the KDELR1 gene was suppressed, no change was
detected. In U266 cells, also, it was found that COPE gene expression increased approximately 1.8
times compared to the control group in 24 hours. It was demonstrated that the rate of apoptotic
cells increased in the siRNA treated cell group compared to the control group in both cell lines. As a
result of the MTT test, it was determined cell proliferation decreased by 62% in U266 cells and by
37% in RPMI8226 cells, especially at the 24th hour.
Conclusion: In this study, we found that suppression of KDELR1 gene expression decreased the
viability of MM cells and triggered apoptosis. Similar studies have shown that the KDELR1 gene
regulates cell homeostasis under cell stress conditions and has different activities in different cells.
Our results also reveal that KDELR1 has an important function in maintaining cell homeostasis in MM
exposed to continuous ER stress. It also features the first functional study with the KDELR1 gene in
U266 and RPMI8266 cells.
Disclosure Statement: The authors declare no conflict of interest