Wang Yinghao, Tang Junjie, Liu Yaoming, Zhang Zhihui, Zhang Hongwei, Ma Yujun, Wang Xinyue, Ai Siming, Mao Yuxiang, Zhang Ping, Chen Shuxia, Li Jinmiao, Gao Yang, Cheng Chao, Li Cheng, Su Shicai, Lu Rong
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.
iScience. 2024 Aug 15;27(9):110725. doi: 10.1016/j.isci.2024.110725. eCollection 2024 Sep 20.
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 and models. This study emphasizes ALDOA as a promising target for innovative RB therapies, with potential implications for altering tumor energy metabolism.
本研究旨在阐明醛缩酶A（ALDOA）在视网膜母细胞瘤（RB）中的关键作用，并评估ALDOA抑制剂衣康酸在阻碍RB进展方面的潜力。利用单细胞RNA测序，ALDOA在多种细胞类型中始终呈现过表达，尤其是在视锥前体细胞、视网膜瘤样细胞和视网膜母细胞瘤样细胞中。这种高表达在RB组织和细胞系中得到验证。敲低ALDOA可显著降低RB细胞活力，阻碍集落形成，并诱导明显的代谢改变。RNA测序分析确定SUSD2、ARHGAP27和CLK2为与ALDOA相关的下游基因。衣康酸的应用在抑制RB细胞增殖方面显示出效果，这在[具体模型1]和[具体模型2]模型中得到验证。本研究强调ALDOA作为创新RB疗法的一个有前景的靶点，对改变肿瘤能量代谢具有潜在意义。
