Aldoa, also known as aldolase A, is a crucial glycolytic enzyme. It participates in glycolysis, a metabolic pathway that breaks down glucose to produce energy in the form of ATP. Glycolysis is essential for normal cellular energy metabolism and is also significantly upregulated in many cancer cells, highlighting the importance of Aldoa in energy-related biological processes [1,2,3,5,6,8].

In various diseases, Aldoa shows distinct effects. In cancer, multiple studies indicate its oncogenic role. For instance, in colon cancer, the POU2F1-ALDOA axis enhances glycolysis and the pentose phosphate pathway, promoting cell proliferation and chemoresistance [1]. In retinoblastoma, Aldoa is overexpressed, and its knockdown reduces cell viability and induces metabolic alterations [2]. In breast cancer, an alternative splicing event in Aldoa confers tamoxifen resistance [4]. In pancreatic cancer, Aldoa inhibits cell cycle arrest induced by DNA damage via the ATM-PLK1 pathway, promoting cancer development [9]. In addition, in vascular calcification, the orphan nuclear receptor NR4A3 enhances glycolysis by directly binding to the promoter regions of Aldoa and PFKL [5]. In contrast, in cardiomyocytes, Aldoa protects against hypoxia/reperfusion-induced apoptosis and oxidative stress by regulating the VEGF/Notch 1/Jagged 1 pathway [7].

In conclusion, Aldoa is a key glycolytic enzyme with diverse functions. Its dysregulation is involved in multiple disease conditions, especially cancer, where it often promotes tumor progression. The study of Aldoa using in vivo models, such as gene knockout or knockdown in cells and animals, has provided valuable insights into its role in these diseases, potentially paving the way for new therapeutic strategies targeting Aldoa-related pathways [1,2,4,5,6,7,8,9].

References:

1. Lin, Jinguan, Xia, Longzheng, Oyang, Linda, Zhou, Yujuan, Liao, Qianjin. 2022. The POU2F1-ALDOA axis promotes the proliferation and chemoresistance of colon cancer cells by enhancing glycolysis and the pentose phosphate pathway activity. In Oncogene, 41, 1024-1039. doi:10.1038/s41388-021-02148-y. https://pubmed.ncbi.nlm.nih.gov/34997215/

2. Wang, Yinghao, Tang, Junjie, Liu, Yaoming, Su, Shicai, Lu, Rong. 2024. Targeting ALDOA to modulate tumorigenesis and energy metabolism in retinoblastoma. In iScience, 27, 110725. doi:10.1016/j.isci.2024.110725. https://pubmed.ncbi.nlm.nih.gov/39262779/

3. Gao, Qiang, Zhu, Hongwen, Dong, Liangqing, Zhou, Hu, Fan, Jia. . Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma. In Cell, 179, 561-577.e22. doi:10.1016/j.cell.2019.08.052. https://pubmed.ncbi.nlm.nih.gov/31585088/

4. Yu, Shiyi, Wu, Rui, Si, Yue, Dong, Weibing, Sun, Haibo. 2024. Alternative splicing of ALDOA confers tamoxifen resistance in breast cancer. In Oncogene, 43, 2901-2913. doi:10.1038/s41388-024-03134-w. https://pubmed.ncbi.nlm.nih.gov/39164523/

5. Ma, Wenqi, Jia, Kangni, Cheng, Haomai, Zhang, Ruiyan, Yan, Xiaoxiang. 2024. Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation. In Circulation research, 134, 1427-1447. doi:10.1161/CIRCRESAHA.123.323699. https://pubmed.ncbi.nlm.nih.gov/38629274/

6. Song, Junjiao, Li, Hongquan, Liu, Yanfang, Chen, Zhiao, He, Xianghuo. 2023. Aldolase A Accelerates Cancer Progression by Modulating mRNA Translation and Protein Biosynthesis via Noncanonical Mechanisms. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2302425. doi:10.1002/advs.202302425. https://pubmed.ncbi.nlm.nih.gov/37431681/

7. Luo, Gaiying, Wang, Rui, Zhou, Hui, Liu, Xiaoling. 2020. ALDOA protects cardiomyocytes against H/R-induced apoptosis and oxidative stress by regulating the VEGF/Notch 1/Jagged 1 pathway. In Molecular and cellular biochemistry, 476, 775-783. doi:10.1007/s11010-020-03943-z. https://pubmed.ncbi.nlm.nih.gov/33089381/

8. Kuang, Qiwen, Liang, Yuxiang, Zhuo, Yangjia, Zheng, Yu, Zhong, Weide. 2021. The ALDOA Metabolism Pathway as a Potential Target for Regulation of Prostate Cancer Proliferation. In OncoTargets and therapy, 14, 3353-3366. doi:10.2147/OTT.S290284. https://pubmed.ncbi.nlm.nih.gov/34079281/

9. Chen, Haidi, Ye, Zeng, Xu, Xiaowu, Ji, Shunrong, Xu, Wenyan. 2021. ALDOA inhibits cell cycle arrest induced by DNA damage via the ATM-PLK1 pathway in pancreatic cancer cells. In Cancer cell international, 21, 514. doi:10.1186/s12935-021-02210-5. https://pubmed.ncbi.nlm.nih.gov/34565365/