Tr‐KIT Downstream Regulation by YY1 and NFYA Transcription Factors Knockdown in Prostate Cancer Cells

• Published in: Genes chromosomes & cancer Vol. 64; no. 7; pp. e70063 - n/a
• Main Authors: Ergun, Sercan, Arı, Ferda, Benli, Erdal, Altay, Diler Us, Noyan, Tevfik, Erdem, Havva, Arıcı, Yeliz Kaşko, Akgün, Oğuzhan, Aslan, Senanur
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.07.2025; Wiley Subscription Services, Inc
• Subjects: Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Cell viability; c‐KIT; Fyn protein; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Knockdown Techniques; Humans; Imatinib; Imatinib Mesylate - pharmacology; Kinases; Male; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Protein-tyrosine kinase receptors; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Sam68; Transcription factors; tr‐KIT; YY1 protein; YY1 Transcription Factor - genetics; YY1 Transcription Factor - metabolism; tr‐KIT; imatinib; prostate cancer; Sam68; c‐KIT
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.70063

ABSTRACT Background Prostate cancer is a common and deadly cancer among men and has been the subject of many patients in its diagnosis and treatment. Imatinib, a tyrosine kinase inhibitor, can slow tumor formation by targeting c‐KIT, an oncogenic receptor tyrosine kinase protein over‐expressed in PCa cases. However, Imatinib has no effect on tr‐KIT, a truncated form of c‐KIT, which is over‐expressed in PCa and is associated with neoplastic transformation. In this study, it is aimed to answer whether the anti‐proliferative efficacy of Imatinib on PCa cells could be enhanced by inhibition of tr‐KIT specific transcription factors. Methods and Results For this purpose, gene expression analysis and cell viability assays were performed in LNCaP prostate cancer cells to investigate the effects of inhibition of transcription factors controlling tr‐KIT expression (YY1 and NFYA) in combination with Imatinib administration. As a result, YY1 and NFYA were identified as tr‐KIT‐specific transcription factors and found that their knockdown increased the effectiveness of Imatinib mesylate treatment on LNCaP cells. The study also analyzed the gene expression changes of c‐KIT, FYN, PLCγ1, and SAM68 genes and found that SAM68 expression decreased with NFYA and YY1 knockdown, suggesting the existence of other unknown mediators in the tr‐KIT pathway. Conclusions All in all, this study demonstrates that tr‐KIT may be a potential pharmacological target for prostate cancer treatment and that inhibition of the transcription factors YY1 and NFYA may enhance the efficacy of Imatinib. SAM68 was found to be the most affected protein by the treatments, guiding future research.