Epigenetic repression of de novo cysteine synthetases induces intra-cellular accumulation of cysteine in hepatocarcinoma by up-regulating the cystine uptake transporter xCT

• DOI: 10.1186/s40170-024-00352-4
• Publication Date: 2024-08-07T08:03:47Z
• Authors: Tomoaki Yamauchi; Yumi Okano; Daishu Terada; Sai Yasukochi; Akito Tsuruta; Yuya Tsurudome; Kentaro Ushijima; Naoya Matsunaga; Satoru Koyanagi; Shigehiro Ohdo
• Keywords: Reprogramming; Cysteine Metabolism

The metabolic reprogramming of amino acids is critical for cancer cell growth and survival. Notably, intracellular accumulation cysteine often observed in various cancers, suggesting its potential role alleviating the oxidative stress associated with rapid proliferation. liver primary organ biosynthesis, but much remains unknown about alterations their mechanisms hepatocellular carcinoma cells. RNA-seq data from patients hepatocarcinoma were analyzed using TNMplot database. underlying mechanism oncogenic alteration metabolism was studied mice implanted BNL 1ME A.7 R.1 hepatocarcinoma. Database analysis revealed that expression enzymes involved de novo synthesis down-regulated accompanying increased cystine uptake transporter xCT. Similar gene have also been a syngeneic mouse model enhanced DNA methyltransferase murine cells caused methylation upstream regions genes, thereby repressing expression. Conversely, suppression healthy induced xCT by up-regulating oxidative-stress response factor NRF2, indicating reduced repulsively increases via expression, leading to accumulation. Furthermore, pharmacological inhibition activity decreased levels suppressed tumor mice. Our findings indicate an highlight efficacy as viable therapeutic target cancer.