Page 29 - SDIR5 Abstract book 21 12 2021.

RADIOBIOLOGY

The Interrelationship between FYN and miR-128/193a-5p/494 in Imatinib Resistance in
Prostate Cancer

2
1,2
3
3
1
Sercan ERGÜN , Oğuzhan AKGÜN , Neslihan TAŞKURT HEKİM , Senanur ASLAN , Ferda ARI , Sezgin
2,4
1,2
GÜNEŞ , Ümmet ABUR
1 Department of Medical Biology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
2 Department of Multidisciplinary Molecular Medicine, Graduate School of Health Sciences, Ondokuz Mayis
University, Samsun, Turkey
3 Department of Biology, Faculty of Science and Arts, University of Uludağ, Bursa, Turkey
4 Department of Medical Genetics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

Background: C-KIT is a receptor tyrosine kinase with oncogenic properties overexpressed in PCa cases.
Through the use of an alternative promoter, a truncated c-KIT protein (tr-KIT) of 30-50 kDa is generated,
lacking the extracellular and transmembrane domain. Tr-KIT promotes the formation of a multi-molecular
complex composed by FYN, PLCγ1 and SAM68. Imatinib blocks the activity of full-length c-KIT but has no
effect on tr-KIT. LNCaP is the human PCa cell line that shows tr-KIT overexpression and PC3 does not show
tr-KIT overexpression. Also, LNCaP and PC3 are regarded as relatively resistant to both radiation-induced
clonogenic death and apoptosis. miR-128/193a-5p/494 are miRNAs targeting FYN, PLCγ1 and SAM68
combinatorily and they are related with radiosensitivity in different types of cancer. The question of the
study is that: can miR-128/193a-5p/494 be related with imatinib resistance in PCa? Material and Methods:
LNCaP and PC3 cells were treated with imatinib in IC50 doses. Before and after imatinib administration,
RNA was isolated and cDNA conversion was performed. By qPCR analysis, expression changes of tr-KIT
specific pathway elements and miR-128/193a-5p/494 analyzed before and after imatinib administration.
Results: After imatinib administration, miR-128/193a-5p/494 were overexpressed statistically significantly
in LNCaP cells while they were downregulated statistically significantly in PC3 cells (p<0.05). Also, FYN was
upregulated in LNCaP cells (p<0.05) but there was no change in PC3 after imatinib administration.
Conclusion: In LNCaP cells having tr-KIT acitivity, especially upregulation of FYN may sponge miR-128/193a-
5p/494 and downregulate their transcriptional activity. So, miR-128/193a-5p/494 may have critical role in
imatinib resistance via tr-KIT pathway.
Keywords: Prostate cancer, imatinib resistance, truncated KIT (tr-KIT), FYN, miRNA sponging
Funding: This study has been financed by Scientific Research Projects Commission of Ondokuz Mayıs
University (Project number: PYO.TIP.1902.21.001).

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