A major problem in prostate cancer (PCa) management is the development of drug resistance. It is known that there are changes in PCa biology upon prolonged treatment with drugs, including anti-androgen drugs that alter cellular signaling processes leading to the development of castration resistant PCa. MicroRNAs (miRNAs) are regulatory molecules that modulate gene expression through inhibition of protein translation and modulate cellular functions. Altered expression of miRNAs is often noted in drug resistant cancer including PCa. Studies from our laboratory have identified a number of down-regulated miRNAs in PCa, including miR-l 7-92a miRNAs. Frabin (FGD4) is a target of the miR-l 7-92a cluster that was found to be up-regulated in PCa cells. For this paper’s investigation, an FGD4 knockdown approach was used to identify the effects on cell viability, cell cycle progression, cell migration and drug sensitivity. Two PCa cells lines, LNCaP-104S (androgen sensitive) and PC-3 (androgen independent), were used for our studies. MTS assays for both cell lines showed significant reduction in cell viability following knockdown of FGD4 compared to transfection with control siRNAs. Cell cycle analysis revealed an arrest in the G2/M phase of the cells that were transfected with FGD4 siRNAs. Cell migration assays revealed a decrease in migration rate of PC-3 cells after knockdown, which supports the involvement of FGD4 in actin- cytoskeleton rearrangement. Treatments with anti-mitotic drug Docetaxel (PC-3) or androgen receptor antagonist bicalutamide/Casodex (LNCaP-104S) showed improved sensitivity of the FGD4 siRNA treated cells to these drugs. Our results suggest the potential for FGD4 knockdown to be used in combination with currently used drugs, increasing the effectiveness of frontline chemotherapeutics.
Bachelor of Science (B.S.)
College of Medicine
Burnett School of Biomedical Sciences
Orlando (Main) Campus
Length of Campus-only Access
Bossan, Alexia M., "The Role of Frabin (FGD4) in Aggressive Prostate Cancer" (2017). Honors in the Major Theses. 162.