Abstract
Purpose :
Our genomic and transcriptomic studies of retinoblastoma tumors consistently showed the dysregulation of Kinesin family member 14 (KIF14), a potential oncogene involved in the tumorigenesis of multiple cancers. However, its role in retinoblastoma (RB) tumor progression was not fully studied. Hence we aim to investigate the role of KIF14 in RB tumor progression and effect of its suppression.
Methods :
Following the genomic/transcriptomic studies, expression of KIF14 was analysed at RNA and protein levels by RT-qPCR and western blot respectively in RB cell lines and patient tumors and correlated with clinical data. Pharmacological inhibition of KIF14 was done using a small molecule inhibitor (Ispinesib) in RB-patient derived primary culture and cell lines. KIF14-inhibited cells were functionally analysed for its effect by growth kinetics, Matrigel invasion, in-vitro chemosensitivity and TUNEL assays.
Results :
The expression of KIF14 was found to be markedly elevated in RB tumors and cell lines at transcript and protein levels. IC50 concentration of Ispinesib was determined with varying concentrations of the drug. The KIF14-inhibited cells showed reduced viability, cell proliferation, and cell invasion with increased apoptosis. Enhanced sensitivity to existing chemotherapeutic drugs affirmed its role in chemoresistance.
Conclusions :
Increased expression of KIF14 promoting tumorigenesis in retinoblastoma was noted. Suppression of KIF14 with small molecule inhibitor showed reduced viability, cell proliferation and invasion, and increased apoptosis. Thus, targeting KIF14 in patients with chemoresistance will improve the treatment efficacy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.