Abstract
Purpose :
This study aims to investigate the significance of aldolase A (ALDOA) in retinoblastoma (RB) and to evaluate the potential of the ALDOA inhibitor itaconate in inhibiting RB progression.
Methods :
Single-cell RNA sequencing (scRNA-seq) datasets derived from normal retinal and RB samples were integrated to characterize ALDOA expression patterns at the single-cell level. ALDOA expression was validated in RB cell lines and patient tissue using qPCR, WB, and IHC staining. SiRNA was employed to knock down ALDOA in RB cell lines, and the impact on cell viability and metabolism was assessed. RNA-seq was performed on RB cells after ALDOA knockdown. In vitro and in vivo experiments were conducted to assess itaconate’s anti-tumor effects.
Results :
ALDOA consistently exhibited overexpression across multiple cell types, with particularly elevated levels in cone precursor cells, retinoma-like cells, and retinoblastoma-like cells. This heightened ALDOA expression was also confirmed in both RB tissues and cell lines. ALDOA knockdown led to a notable reduction in RB cell viability and impaired colony formation, accompanied by significant metabolic alterations. RNA-seq analysis unveiled SUSD2, ARHGAP27, and CLK2 as downstream genes associated with ALDOA. The application of itaconate effectively inhibit RB cell proliferation, demonstrating consistent results in both in vitro and in vivo models.
Conclusions :
The study underscores ALDOA's role in promoting RB growth by enhancing aerobic glycolysis. Inhibiting ALDOA offers potential in restraining RB tumorigenesis and altering tumor energy metabolism. ALDOA emerges as a significant target for novel therapies in RB treatment.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.