YY1 and NFYA: Potential tr-KIT Specific Transcription Factors in Prostate Cancer

Year 2022, , 202 - 207, 31.05.2022

Sercan Ergün , Ferda Arı , Erdal Benli , Diler Us Altay , Tevfik Noyan , Havva Erdem , Yeliz Kaşko Arıcı

https://doi.org/10.19127/mbsjohs.1001931

Cited By: 1

Abstract

Objective: Via the use of an alternative promoter, a truncated c-KIT protein (tr-KIT) of 30-50 kDa is generated, lacking extracellular and transmembrane domains. Moreover, over-expression of tr-KIT, a stronger activator than c-KIT, appears to be specific to prostate cancer (PCa). Also, Imatinib, a tyrosine kinase inhibitor, blocks the activity of full-length c-KIT but has no effect on tr-KIT in PCa. Tr-KIT has its own nuclear factor binding site. However, the transcription factors (TFs) binding to this region specific to tr-KIT are not known yet. This study was conducted to define the most potential TFs specific for tr-KIT via in silico analysis.
Methods: Tr-KIT potential TF binding sequence was uploaded into Tfsitescan database. Five TFs with the highest potential binding to this sequence were selected. Transcriptomic data of LNCaP (PCa expressing tr-KIT), PC3 (PCa not expressing tr-KIT) and RWPE-1 (normal prostate) cell lines (GSM1647378, GSE36022 and GSM738189, respectively) from Gene Expression Omnibus (GEO) database were compared for gene expression levels of pre-defined potential tr-KIT specific TFs using DESeq package of R-program. Finally, two TFs having higher expression levels in both LNCaP and PC3 compared to RWPE-1 and higher expression levels in LNCaP compared to PC3 were detected.
Results: Five TFs having the highest potential were selected as: YY1, c-MYB, IL8, NFYA and TCF3. Via in silico analysis performed, it was found that YY1 and NFYA have the highest potential to be tr-KIT specific TFs in PCa, among them.
Conclusion: YY1 and NFYA TFs may take a role in formation of tr-KIT in PCa.

Keywords

Prostate cancer, transcription factors, gene expression regulation

Project Number

This study was carried out within the scope of TUBITAK 3501 project, numbered 119Z574.

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