Targeting ALDOA to modulate tumorigenesis and energy metabolism in retinoblastoma
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 <i>in vitro</i> and <i>in vivo</i> models. This study emphasizes ALDOA as a promising target for innovative RB therapies, with potential implications for altering tumor energy metabolism.
Authors
- Yaoming Liu (ORCID: https://orcid.org/0009-0001-5642-4422)
- Yujun Ma (ORCID: https://orcid.org/0000-0002-0577-959X)
- Hongwei Zhang
- Siming Ai
- Chao Cheng (ORCID: https://orcid.org/0000-0003-3571-8154)
- Jinmiao Li (ORCID: https://orcid.org/0000-0002-5130-4616)
- Shuxia Chen (ORCID: https://orcid.org/0000-0002-3090-847X)
- Cheng Li (ORCID: https://orcid.org/0000-0002-2022-1746)
- Ping Zhang (ORCID: https://orcid.org/0000-0002-8164-542X)
- Xinyue Wang (ORCID: https://orcid.org/0000-0003-4231-617X)
- Zhihui Zhang (ORCID: https://orcid.org/0000-0003-3111-2665)
- Yinghao Wang (ORCID: https://orcid.org/0000-0002-1928-0538)
- Junjie Tang (ORCID: https://orcid.org/0000-0003-3185-9929)
- Rong Lu (ORCID: https://orcid.org/0000-0002-5716-6955)
- Shicai Su
- Yuxiang Mao
- Yang Gao (ORCID: https://orcid.org/0000-0002-7910-3787)
Institutions
- Sun Yat-sen University (CN)
Publication Details
- Journal
- iScience
- Published
- 2024-08-15
- DOI
- https://doi.org/10.1016/j.isci.2024.110725
- Citations
- 6
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 1.71
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province