FABP5 can substitute for androgen receptor in malignant progression of prostate cancer cells.

Naeem, Abdulghani A, Abdulsamad, Saud A, Zeng, Hao, He, Gang, Jin, Xi, Zhang, Jiacheng, Alenezi, Bandar T, Ma, Hongwen, Rudland, Philip S ORCID: 0000-0002-7491-0846 and Ke, Youqiang ORCID: 0000-0001-5341-8644 (2024) FABP5 can substitute for androgen receptor in malignant progression of prostate cancer cells. International journal of oncology, 64 (2). 18-.

PDF
ijo_64_2_5606_PDF.pdf - Open Access published version
Download (9MB) | Preview

Official URL: http://dx.doi.org/10.3892/ijo.2023.5606

Abstract

Fatty acid‑binding protein 5 (FABP5) and androgen receptor (AR) are critical promoters of prostate cancer. In the present study, the effects of knocking out the FABP5 or AR genes on malignant characteristics of prostate cancer cells were investigated, and changes in the expression of certain key proteins in the FABP5 (or AR)‑peroxisome proliferator activated receptor‑γ (PPARγ)‑vascular endothelial growth factor (VEGF) signaling pathway were monitored. The results obtained showed that FABP5‑ or AR‑knockout (KO) led to a marked suppression of the malignant characteristics of the cells, in part, through disrupting this signaling pathway. Moreover, FABP5 and AR are able to interact with each other to regulate this pathway, with FABP5 controlling the dominant AR splicing variant 7 (ARV7), and AR, in return, regulates the expression of FABP5. Comparisons of the RNA profiles revealed the existence of numerous differentially expressed genes (DEGs) comparing between the parental and the FABP5‑ or AR‑KO cells. The six most abundant changes in DEGs were found to be attributable to the transition from androgen‑responsive to androgen‑unresponsive, castration‑resistant prostate cancer (CRPC) cells. These findings have provided novel insights into the complex molecular pathogenesis of CRPC cells, and have demonstrated that interactions between FABP5 and AR contribute to the transition of prostate cancer cells to an androgen‑independent state. Moreover, gene enrichment analysis revealed that the most highly enriched biological processes associated with the DEGs included those responsive to fatty acids, cholesterol and sterol biosynthesis, as well as to lipid and fatty acid transportation. Since these pathways regulated by FABP5 or AR may be crucial in terms of transducing signals for cancer cell progression, targeting FABP5, AR and their associated pathways, rather than AR alone, may provide a new avenue for the development of therapeutic strategies geared towards suppressing the malignant progression to CRPC cells.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Tumor, Humans, Vascular Endothelial Growth Factor A, Receptors, Androgen, Androgens, Gene Expression Regulation, Neoplastic, Male, Fatty Acid-Binding Proteins, Prostatic Neoplasms, Castration-Resistant
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	02 Jan 2024 16:31
Last Modified:	10 Feb 2024 01:41
DOI:	10.3892/ijo.2023.5606
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3177638