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

Year 2022, Volume: 8 Issue: 2, 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.

References

• 1. Wu P, Cao Z, Wu, S. New progress of epigenetic biomarkers in urological cancer. Dis Markers 2016; 9864047.
• 2. Imura M, Kojima Y, Kubota Y, Hamakawa T, Yasui T, Sasaki S, Hayashi Y, Kohri K. Regulation of cell proliferation through a KIT‐mediated mechanism in benign prostatic hyperplasia. Prostate 2012; 72(14): 1506-1513.
• 3. Cardoso HJ, Figueira MI, Socorro S. The stem cell factor (SCF)/c-KIT signalling in testis and prostate cancer. Cell Commun Signal 2017; 11(4): 297-307.
• 4. Paronetto MP, Farini D, Sammarco I, Maturo G, Vespasiani G, Geremia R, Rossi P, Sette C. Expression of a truncated form of the c-Kit tyrosine kinase receptor and activation of Src kinase in human prostatic cancer. Am J Pathol 2004; 164(4): 1243-1251.
• 5. Ergun S, Altay DU, Gunes S, Buyukalpelli R, Karahan SC, Tomak L, Abur U. Tr-KIT/c-KIT ratio in renal cell carcinoma. Mol Biol Rep 2019; 46(5): 5287-94.
• 6. Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, Snell GP, Zou H, Sang BC, Wilson KP. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem 2004; 279(30): 31655-31663.
• 7. Albanesi C, Geremia R, Giorgio M, Dolci S, Sette C, Rossi P. A cell-and developmental stage-specific promoter drives the expression of a truncated c-kit protein during mouse spermatid elongation. Development 1996; 122(4): 1291-1302.
• 8. Ghosh D. Object-oriented transcription factors database (ooTFD). Nucleic Acids Res 2000; 28(1): 08-310.
• 9. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol 2010; 11(10): R106.
• 10. Yang T, An Z, Zhang C, Wang Z, Wang X, Liu Y, Xu Y. HnRNPM is a potential mediator of YY1 which promotes EMT in prostate cancer cells. Prostate 2019; 79(11): 1199-1210.
• 11. Camacho-Moctezuma B, Quevedo-Castillo M, Melendez-Zajgla J, Aquino-Jarquin G, Martinez-Ruiz, GU. YY1 negatively regulates the XAF1 gene expression in prostate cancer. Biochem Bioph Res Co 2019; 508(3): 973-979.
• 12. Huang Y, Tao T, Liu C, Guan H, Zhang G, Ling Z, Chen M. Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer. Int J Oncol 2017; 50(2): 421-431.
• 13. Zhang HT, Zhang D, Zha ZG, Hu CD. Transcriptional activation of PRMT5 by NF-Y is required for cell growth and negatively regulated by the PKC/c-Fos signaling in prostate cancer cells. BBA Gene Regul Mech 2014; 1839(11): 1330-1340.
• 14. Chan QK, Lam HM, Ng CF, Lee AY, Chan ES, Ng HK, Lau KM. Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G 2 cell-cycle arrest. Cell Death Differ 2010; 17(9): 1511-1523.