Loss-of-Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia was written by Niu, Yi;Lin, Ziyou;Wan, Arabella;Sun, Lei;Yan, Shijia;Liang, Heng;Zhan, Siyue;Chen, Dongshi;Bu, Xianzhang;Liu, Peiqing;Chen, Ceshi;He, Weiling;Lu, Xiongbin;Wan, Guohui. And the article was included in Hepatology (Hoboken, NJ, United States) in 2021.Electric Literature of C11H12N4O3S This article mentions the following:
Hypoxia is a common feature of the tumor microenvironment (TME), which promotes tumor progression, metastasis, and therapeutic drug resistance through a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclin. development of this approach is lacking in the study of HCC. From a genome-wide CRISPR/CRISPR-associated 9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia. Knockdown of ALDOA in HCC cells leads to lactate depletion and consequently inhibits tumor growth. Supplementation with lactate partly rescues the inhibitory effects mediated by ALDOA knockdown. Upon hypoxia, ALDOA is induced by hypoxia-inducible factor-1α and fat mass and obesity-associated protein-mediated N6-methyladenosine modification through transcriptional and posttranscriptional regulation, resp. Anal. of The Cancer Genome Atlas shows that elevated levels of ALDOA are significantly correlated with poor prognosis of patients with HCC. In a screen of Food and Drug Administration-approved drugs based on structured hierarchical virtual platforms, we identified the sulfamonomethoxine derivative compound 5 (cpd-5) as a potential inhibitor to target ALDOA, evidenced by the antitumor activity of cpd-5 in preclin. patient-derived xenograft models of HCC. Our work identifies ALDOA as an essential driver for HCC cell growth under hypoxia, and we demonstrate that inhibition of ALDOA in the hypoxic TME is a promising therapeutic strategy for treating HCC. In the experiment, the researchers used many compounds, for example, 4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3Electric Literature of C11H12N4O3S).
4-Amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide (cas: 1220-83-3) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Electric Literature of C11H12N4O3S
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia