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Targeting ALDOA to modulate tumorigenesis and energy metabolism in retinoblastoma

Authors :
Yinghao Wang
Junjie Tang
Yaoming Liu
Zhihui Zhang
Hongwei Zhang
Yujun Ma
Xinyue Wang
Siming Ai
Yuxiang Mao
Ping Zhang
Shuxia Chen
Jinmiao Li
Yang Gao
Chao Cheng
Cheng Li
Shicai Su
Rong Lu
Source :
iScience, Vol 27, Iss 9, Pp 110725- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: This study aims to elucidate the pivotal role of aldolase A (ALDOA) in retinoblastoma (RB) and evaluate the potential of the ALDOA inhibitor itaconate in impeding RB progression. Utilizing single-cell RNA sequencing, ALDOA consistently exhibits overexpression across diverse cell types, particularly in cone precursor cells, retinoma-like cells, and retinoblastoma-like cells. This heightened expression is validated in RB tissues and cell lines. ALDOA knockdown significantly diminishes RB cell viability, impedes colony formation, and induces notable metabolic alterations. RNA-seq analysis identifies SUSD2, ARHGAP27, and CLK2 as downstream genes associated with ALDOA. The application of itaconate demonstrates efficacy in inhibiting RB cell proliferation, validated through in vitro and in vivo models. This study emphasizes ALDOA as a promising target for innovative RB therapies, with potential implications for altering tumor energy metabolism.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
9
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.2f6098c10bc456ab313f0577df99682
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.110725