Biology subjects

Duzgun, D.

Publications and source records attributed to Duzgun, D..

3 recordsLinked to original sources

bioRxiv2026

SRPK1 is a determinant of chemoresistance to Docetaxel in prostate cancer

Docetaxel is a major therapeutic option for advanced prostate cancer, but the development of acquired resistance substantially limits its clinical efficacy. Although multiple mechanisms have been implicated in docetaxel resistance, the upstream regulatory pathways coordinating these phenotypes remain incompletely understood. Here, we investigated the role of serine/arginine-rich protein kinase 1 (SRPK1), a key regulator of pre-mRNA splicing, in acquired docetaxel resistance in prostate cancer. Docetaxel-resistant PC3 cells showed increased SRPK1 expression at both the protein and RNA levels. Genetic depletion or pharmacological inhibition of SRPK1 substantially restored docetaxel sensitivity, whereas ectopic SRPK1 expression in parental PC3 cells increased resistance. Mechanistically, SRPK1 inhibition reduced expression of {beta}III-tubulin and restored docetaxel-induced microtubule bundling. SRPK1 inhibition also increased apoptosis in resistant cells, accompanied by increased cleavage of caspase-8, caspase-9 and PARP. In parallel, SRPK1 inhibition restored E-cadherin expression and reduced the enhanced migratory phenotype of resistant cells. At the signalling and RNA-processing levels, docetaxel-resistant cells exhibited increased EGFR expression and increased phosphorylation of the SRPK1 substrate SRSF1. SRSF1 depletion partially restored docetaxel sensitivity, supporting an EGFR-SRPK1-SRSF1 pathway in resistance. Importantly, inhibition of SRPK1 or depletion of SRSF1 altered the splicing of apoptosis- and microtubule-associated genes, increasing the pro-apoptotic Bcl-xS and MCL-1S isoforms and shifting tau splicing towards 3R at the expense of 4R. Collectively, these findings identify SRPK1 as a central regulator of multiple phenotypic and molecular features of docetaxel resistance in prostate cancer. Targeting SRPK1-dependent splicing may therefore represent a strategy to re-sensitize resistant prostate cancer cells to docetaxel.

cancer biology↗

bioRxiv2025

Clinical Implications of SRPK1 Expression in Human Tumours: A Comprehensive Pan-Cancer Analysis Based on Multi-Omics Databases

Serine/arginine-rich protein kinase 1 (SRPK1), which primarily regulates alternative splicing (AS), has been implicated in various malignancies. However, the comprehensive expression landscape and clinical relevance of SRPK1 across diverse tumour types have not been systematically investigated. Chemoresistance remains a formidable obstacle in cancer treatment, accounting for nearly 90% of treatment failures and leading to poor patient survival. Aberrant AS, often driven by splicing factors like SRPK1, is a mechanism cancer cells exploit to overcome chemotherapy-induced cytotoxicity. With that, this study tested the hypothesis of tumour-specific alterations in SRPK1 expression as novel therapeutic targets through a pan-cancer analysis of SRPK1 using multi-omics data, obtained from public databases, including TCGA, CPTAC, GEPIA2, and drug sensitivity platforms. The analysis specifically assessed the pan-cancer expression landscape of SRPK1 at the mRNA and protein levels and its prognostic implications across different cancer types (breast, colon, and prostate cancers), functional analysis of SRPK1-associated splicing network, and its expression in correlation with predicted drug sensitivity. The results revealed the correlations of high SRPK1 expression with worse overall and disease-free survival in a cancer-specific manner and resistance to standard-of-care agents like cisplatin and docetaxel. The integrative multi-omics approach in this study provided a robust foundation for understanding the complex, multifaceted role of SRPK1 in tumour-specific chemoresistance.

bioinformatics↗

bioRxiv2025

Modulators of epithelial-mesenchymal transitions in prostate cancer: potential for novel therapeutics development

Research in the area of hallmarks of cancer has opened the possibility of designing novel therapeutic interventions based on modulating cancer properties. Interestingly, the epithelial-mesenchymal transition (EMT), important in both tumour growth and metastasis, has not been targeted in prostate cancer (PCa). Previously, in a repositioning screen, three new chemicals that modulate EMT in PCa (named LLSOs) have been found. This study aims to investigate how they work mechanistically as well as the effect of these LLSOs on the properties of PCa cells both in vitro and in vivo. Although LLSOs exhibited varying effects on different cancer cell lines, all of them modulated EMT by inhibiting the migration of PCa cells. LLSO3 also exhibited a significant inhibitory effect on tumour growth in vivo, concomitant with an increase in the expression levels of E-cadherin. Further investigation was conducted to obtain mechanistic insights into the LLSO compounds mode of action. In conclusion, our work strongly supports that LLSO compounds may become important candidates for targeted therapeutics in prostate cancer.

cancer biology↗